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1.
Reprod Biol Endocrinol ; 22(1): 101, 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118049

RESUMO

PURPOSE: To determine the factors influencing the likelihood of biochemical pregnancy loss (BPL) after transfer of a euploid embryo from preimplantation genetic testing for aneuploidy (PGT-A) cycles. METHODS: The study employed an observational, retrospective cohort design, encompassing 6020 embryos from 2879 PGT-A cycles conducted between February 2013 and September 2021. Trophectoderm biopsies in day 5 (D5) or day 6 (D6) blastocysts were analyzed by next generation sequencing (NGS). Only single embryo transfers (SET) were considered, totaling 1161 transfers. Of these, 49.9% resulted in positive pregnancy tests, with 18.3% experiencing BPL. To establish a predictive model for BPL, both classical statistical methods and five different supervised classification machine learning algorithms were used. A total of forty-seven factors were incorporated as predictor variables in the machine learning models. RESULTS: Throughout the optimization process for each model, various performance metrics were computed. Random Forest model emerged as the best model, boasting the highest area under the ROC curve (AUC) value of 0.913, alongside an accuracy of 0.830, positive predictive value of 0.857, and negative predictive value of 0.807. For the selected model, SHAP (SHapley Additive exPlanations) values were determined for each of the variables to establish which had the best predictive ability. Notably, variables pertaining to embryo biopsy demonstrated the greatest predictive capacity, followed by factors associated with ovarian stimulation (COS), maternal age, and paternal age. CONCLUSIONS: The Random Forest model had a higher predictive power for identifying BPL occurrences in PGT-A cycles. Specifically, variables associated with the embryo biopsy procedure (biopsy day, number of biopsied embryos, and number of biopsied cells) and ovarian stimulation (number of oocytes retrieved and duration of stimulation), exhibited the strongest predictive power.


Assuntos
Aborto Espontâneo , Aneuploidia , Testes Genéticos , Aprendizado de Máquina , Diagnóstico Pré-Implantação , Humanos , Feminino , Gravidez , Diagnóstico Pré-Implantação/métodos , Estudos Retrospectivos , Adulto , Testes Genéticos/métodos , Aborto Espontâneo/diagnóstico , Aborto Espontâneo/genética , Aborto Espontâneo/epidemiologia , Transferência Embrionária/métodos , Blastocisto
2.
Mini Rev Med Chem ; 5(3): 293-305, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15777263

RESUMO

Albumin nanoparticles (NP) were proved to be effective and safe carriers for delivering anticytomegaloviral compounds in the vitreous. NP improved the antiviral activity of both ganciclovir and the phosphodiester oligonucleotide analog to formivirsen. NP appeared to be fusogenic carriers able to target the nucleus of cells. In addition, these drug carriers were well tolerated when administered by the intravitreal route and did not induce autoimmune reactions.


Assuntos
Albuminas/química , Antivirais/administração & dosagem , Citomegalovirus/efeitos dos fármacos , Portadores de Fármacos/química , Nanoestruturas/química , Corpo Vítreo , Animais , Antivirais/química , Antivirais/farmacologia , Linhagem Celular , Olho/virologia , Ganciclovir/administração & dosagem , Ganciclovir/química , Ganciclovir/farmacologia , Humanos , Oligonucleotídeos Antissenso/administração & dosagem , Oligonucleotídeos Antissenso/química , Distribuição Tecidual , Latência Viral
3.
AIDS ; 14(2): 157-61, 2000 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-10708286

RESUMO

OBJECTIVE: To compare adherence and clinical outcome with two modalities of highly active antiretroviral therapy (HAART), in HIV-infected patients. DESIGN: Randomized, open-label, prospective study. SETTING: Tertiary care centre in Spain. PATIENTS: A total of 112 non-naive HIV-infected patients, recruited from March 1998 through August 1998, were studied. INTERVENTIONS: Triple drug therapy with stavudine and lamivudine, plus indinavir or nelfinavir. MAIN OUTCOME MEASURES: Adherence, side-effects, and immunological, virological, and clinical efficacy of treatment were assessed at 3-month intervals. RESULTS: After a median follow-up of 9 months, 32% of patients in the indinavir group versus 50% of those in the nelfinavir group showed adequate adherence in all clinical appointments (P= 0.0559). Adherence was superior in the nelfinavir group in every visit. After 6 months of treatment 48% of subjects in the indinavir group and 70% of those in the nelfinavir group exhibited adequate adherence (P= 0.0311). After 9 months 35% of patients in the indinavir group and 59% of those in the nelfinavir group showed adequate adherence (P= 0.0291). Side-effects provoked discontinuation of treatment in 34% of patients in the indinavir group and 12% of patients in the nelfinavir group (P= 0.0073). Immunological and virological efficacy were similar in both groups. CONCLUSIONS: Adherence to a HAART regimen with stavudine plus lamivudine plus nelfinavir was superior to a regimen with stavudine plus lamivudine plus indinavir. Side-effects provoked more discontinuation of treatment in the indinavir group than in the nelfinavir group.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Lamivudina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Estavudina/uso terapêutico , Adulto , Quimioterapia Combinada , Feminino , Humanos , Indinavir/efeitos adversos , Indinavir/uso terapêutico , Nefropatias/induzido quimicamente , Masculino , Nelfinavir/efeitos adversos , Nelfinavir/uso terapêutico , Cooperação do Paciente , Estudos Prospectivos , Resultado do Tratamento
4.
Neuropharmacology ; 28(3): 291-8, 1989 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-2471111

RESUMO

The antinociceptive effects of substance P and of neurotensin have been determined in rodents after depletion of serotonin (5-HT) or noradrenaline (NA) in the spinal cord. The antinociceptive effect of substance P, given intraventricularly, in rats and mice was blocked after depletion of 5-HT in the spinal cord with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or with the inhibitor of the synthesis of 5-HT, p-chlorophenylalanine (PCPA), but not after depletion of NA in the spinal cord with the neurotoxin 6-hydroxydopamine (6-OHDA). Conversely, the antinociceptive effect of neurotensin in mice was blocked after lesion of spinal NA pathways with 6-OHDA. When 5-HT spinal pathways of mice were lesioned with 5,7-DHT, neurotensin-induced antinociception was blocked 7 but not 15 days after the lesion. p-Chlorophenylalanine failed to prevent this effect of neurotensin. The results suggest that the antinociceptive effect of substance P depends on the integrity of spinal 5-HT neurones, whereas that of neurotensin depends on spinal NA neurones and, only to a limited extent, on 5-HT neurones. It seems that different descending systems are involved in the antinociception elicited by these two neuropeptides.


Assuntos
Analgésicos , Monoaminas Biogênicas/fisiologia , Vias Neurais/fisiologia , Neurotensina/farmacologia , Medula Espinal/fisiologia , Substância P/farmacologia , 5,7-Di-Hidroxitriptamina/farmacologia , Animais , Eletrofisiologia , Fenclonina/farmacologia , Hidroxidopaminas/farmacologia , Injeções Intraventriculares , Masculino , Camundongos , Camundongos Endogâmicos ICR , Norepinefrina/fisiologia , Oxidopamina , Ratos , Ratos Endogâmicos
5.
Peptides ; 7(3): 419-23, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-2430264

RESUMO

Substance P (SP), physalaemin, SP4-11, SP5-11 and the SP5-11 analog DiMe-C7 induce an antinociceptive effect in rats after intraventricular administration. Other tachykinins and the N-terminal fragments of SP are inactive. All antinociceptive peptides increase the Met-enkephalin efflux from slices of rat periaqueductal gray matter and their antinociceptive potency is correlated with their capacity to release Met-enkephalin. The results, discussed in the light of current theories on different tachykinin receptors, suggest that the SP-P receptor subtype may be involved in the control of noxious stimulation elicited by SP at supraspinal levels.


Assuntos
Analgésicos , Encefalina Metionina/metabolismo , Neuropeptídeos/farmacologia , Dor/fisiopatologia , Substância Cinzenta Periaquedutal/metabolismo , Substância P/análogos & derivados , Substância P/farmacologia , Animais , Técnicas In Vitro , Masculino , Fragmentos de Peptídeos/farmacologia , Substância Cinzenta Periaquedutal/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Taquicininas
6.
J Control Release ; 94(1): 217-27, 2004 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-14684285

RESUMO

The goal of this study was to evaluate the potential of albumin nanoparticles as a delivery system for antisense oligonucleotides. Nanoparticles were prepared by a coacervation process and cross-linkage with glutaraldehyde. Phosphodiester (PO) and phosphorotioate (PS) oligonucleotides were either adsorbed on the surface of nanoparticles (PO-NPA and PS-NPA) or incorporated in the nanoparticle matrix (PO-NPB and PS-NPB). When PO-loaded nanoparticles were incubated with phosphodiesterase, only NPB was able to keep the oligonucleotide hybridization capability for at least 60 min. The antiviral activity was evaluated in MRC-5 fibroblasts infected with human cytomegalovirus at a MOI of 0.0035. Both PO nanoparticle formulations significantly increased the antiviral activity of free PO (P<0.001) and NPB showed slightly higher efficacies than NPA (P<0.05). On the other hand, PS exhibited significant higher activity than free PO (P<0.001), however, no significant differences were found between PS-nanoparticle and PO-nanoparticle formulations. These findings were well correlated with the intracellular distribution observed for fluorescent oligonucleotide-loaded albumin nanoparticles. Even these carriers delayed and decreased the uptake of PO by MRC-5 cells, they finally induced a diffused cytoplasmic distribution and major nuclear accumulation. In summary, albumin nanoparticles partially protected a PO against enzymatic degradation and improved their presence in the nucleus and thus, increased its efficiency.


Assuntos
Albuminas/farmacocinética , Antivirais/farmacocinética , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/crescimento & desenvolvimento , Nanotecnologia/métodos , Oligonucleotídeos/farmacocinética , Albuminas/administração & dosagem , Albuminas/química , Antivirais/administração & dosagem , Antivirais/química , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Química Farmacêutica , Citomegalovirus/metabolismo , Estabilidade de Medicamentos , Humanos , Oligonucleotídeos/administração & dosagem , Oligonucleotídeos/química , Ensaio de Placa Viral
7.
Neurosci Lett ; 87(3): 302-6, 1988 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-2454430

RESUMO

In the rat, unilateral dorsal cervicothoracic rhizotomy (C5-T2) resulted in autotomy of the ipsilateral limb. The onset of self-mutilation was variable and attained the maximum degree 8-9 weeks after the dorsal root section. Fifteen and 60 days after the lesion the monoamines dopamine (DA), noradrenaline (NA) and serotonin (5-HT) as well as the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured by high performance liquid chromatography at different levels of the spinal cord. The lesion induced a significant decrease in the spinal levels of DA and NA, both ipsilateral and contralateral to the lesion, not only in the deafferented region but also from T3 downwards. The changes in DA levels were more marked and of earlier onset than those of NA. The decrease in 5-HT and its metabolite 5-HIAA was only observed in the more caudal regions of the non-deafferented ipsilateral cord. The more conspicuous lessening in spinal monoamine levels coincided approximately with the maximum intensity of autotomy. The present results suggest that dorsal rhizotomy induces distant changes in the brainstem nuclei where descending aminergic pathways originate.


Assuntos
Dopamina/metabolismo , Norepinefrina/metabolismo , Serotonina/metabolismo , Medula Espinal/metabolismo , Raízes Nervosas Espinhais/fisiologia , Animais , Vias Eferentes/metabolismo , Vias Eferentes/fisiologia , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Ratos , Ratos Endogâmicos
8.
J Chromatogr A ; 871(1-2): 311-20, 2000 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-10735311

RESUMO

ISIS 2922 is an antisense oligonucleotide with antiviral activity against cytomegalovirus. However, its rapid degradation in biological fluids and its low capacity for diffusion across cell membranes limit its therapeutical use. One possibility to overcome these drawbacks consists of using nanoparticles as drug carriers. The aim of this study was to develop an analytical method for determining the amount of ISIS 2922 loaded into albumin nanoparticles. For this purpose, capillary zone electrophoresis (CZE) was performed on a fused-silica capillary filled with borate buffer (12.5 mM, pH 9.5). Paracetamol was used as an internal standard and a diode-array detection system was set at 270 nm. Under these conditions, the limit of quantitation of ISIS 2922 was 1.27 microg and the precision and accuracy of the method did not exceed 7%. Moreover, the use of paracetamol as internal standard and the quantification by means of a 'corrected area' procedure enabled us to reduce the peak variability and accurately determine the amount of oligonucleotide loaded in the albumin nanoparticles. In summary, this assay is a selective and sensitive CZE method for the accurate quantitation of ISIS 2922 oligonucleotide in albumin nanoparticles.


Assuntos
Antivirais/análise , Portadores de Fármacos , Eletroforese Capilar/métodos , Tionucleotídeos/análise , Sequência de Bases , Tamanho da Partícula , Padrões de Referência , Reprodutibilidade dos Testes
9.
J Drug Target ; 11(4): 197-204, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-14578106

RESUMO

In the present work, we describe the ability of bovine serum albumin (BSA) to improve the cytoplasmatic delivery of a phosphodiester oligonucleotide (PO), whose phosphorotioate analogue is ISIS 2922 (Vitravene). The changes in intensity and lambda(max) in fluorescence spectroscopy and the increase in fluorescence anisotropy upon complex formation between the oligonucleotide and the protein (PO-BSA) were used to determine the dissociation constant, Km=6.3 x 10(-8) M. The stoichiometry of the complex is mainly 1:1, although 2 PO per BSA have been detected at high PO/BSA ratios. The complexation did not protect PO against enzymatic degradation by snake venom phosphodiesterase (0.1 mg/mL). Fluorescence microscopy revealed that PO-BSA complexes showed a decreased uptake and modified pattern of intracellular distribution with a rapid nuclear accumulation (rather than vesicular localization in the cytoplasm observed for free oligonucleotide). The effect was only observed over a certain threshold of BSA concentration (higher than found in media supplemented with 10% serum). By this way, the interaction with albumin increased the antiviral activity of the oligonucleotide, tested by a plaque reduction assay in MRC-5 fibroblasts infected with human cytomegalovirus (strain RC 256) at a MOI of 0.0035. At 10 microM PO concentration, free PO decreased virus plaques to 85% of the control, while PO-BSA complexes reduced to 60%, in the same order than ISIS 2922. The phosphorotioate analogue complexed by BSA (ISIS 2922-BSA) showed the highest activity with 45% of the control plaques.


Assuntos
Antivirais/administração & dosagem , Citomegalovirus/efeitos dos fármacos , Líquido Intracelular/efeitos dos fármacos , Oligonucleotídeos Antissenso/administração & dosagem , Soroalbumina Bovina/administração & dosagem , Animais , Antivirais/farmacocinética , Bovinos , Linhagem Celular , Citomegalovirus/metabolismo , Relação Dose-Resposta a Droga , Humanos , Líquido Intracelular/metabolismo , Oligonucleotídeos Antissenso/farmacocinética , Soroalbumina Bovina/farmacocinética
10.
J Infect ; 41(1): 50-4, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10942640

RESUMO

OBJECTIVES: To evaluate adherence, side effects and efficacy of a modality of highly active antiretroviral therapy (HAART) in HIV-infected patients. METHODS: In a cohort, prospective study, 65 previously treated patients received stavudine plus lamivudine plus nelfinavir. Fifty-three participants (81%) had a history of intravenous drug use. Patients were evaluated at 3-month intervals. The association of adherence with demographic variables, hepatitis C virus infection, number of stopped antiretroviral regimens, HIV RNA level, CD4 cell count, and adverse effects to drugs was assessed. RESULTS: After a median follow-up of 12 months, 30 participants (46%) showed adequate adherence in all visits. An association was observed between adherence and female sex: 18 of 47 men (38%) vs. 12 of 18 women (67%) presented adequate adherence in all visits (P=0. 0416). An association was also observed between adherence and low baseline HIV RNA level (P=0.0229). Discontinuation of treatment took place because of refusal to take medication in 11 participants (17%) and because of side effects in seven participants (11%). Undetectable HIV RNA level was achieved in 26 patients (40%) at 3 months and in lower percentages at months 6, 9 and 12. CONCLUSIONS: Overall adherence to the employed HAART regimen was poor. Female sex and low baseline HIV RNA were associated with better adherence. Refusal to take medications and side effects were the main reasons to stop therapy. At 3 months' follow-up, virological efficacy was achieved in 40% of patients.


Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Lamivudina/uso terapêutico , Nelfinavir/uso terapêutico , Cooperação do Paciente , Inibidores da Transcriptase Reversa/uso terapêutico , Estavudina/uso terapêutico , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Quimioterapia Combinada , Feminino , HIV/efeitos dos fármacos , Infecções por HIV/psicologia , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/normas , Hepatite C , Humanos , Lamivudina/efeitos adversos , Lamivudina/normas , Modelos Logísticos , Masculino , Nelfinavir/efeitos adversos , Nelfinavir/normas , Reação em Cadeia da Polimerase , Estudos Prospectivos , RNA Viral/sangue , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/normas , Estatísticas não Paramétricas , Estavudina/efeitos adversos , Estavudina/normas , Abuso de Substâncias por Via Intravenosa/complicações
11.
J Infect ; 39(2): 141-5, 1999 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10609532

RESUMO

OBJECTIVES: To compare adherence and clinical outcome with highly active antiretroviral therapy (HAART) in intravenous drug users (IDUs) and subjects with other HIV risk behaviours (non-IDUs). METHODS: A total of 133 non-naive HIV-infected patients, 95 (71%) IDUs and 38 (29%) non-IDUs received triple drug therapy with stavudine, lamivudine, and indinavir. Adherence, side effects, and immunological and virological efficacy of treatment were assessed every 3 months. RESULTS: During a median follow-up of 12 months, 43 patients (32% of the total) showed adequate adherence in all clinical appointments. Adherence was superior in non-IDUs than in IDUs in every visit, but a significant difference was found only at 6 months, when 22 (58%) non-IDUs versus 37 (39%) IDUs were adherent (P = 0.047). Mildly increased bilirubin was observed in 69 (52%) patients, and renal colic in 34 (26%). No difference in side effects was found between IDUs and non-IDUs. After 6 months of treatment, 35 (43%) participants presented a CD4 cell count increase >100x10(6)/l, and 47 (58%) achieved undetectable HIV RNA (lower limit of detection: 200 copies/ml). CD4 cell count and HIV RNA responses were similar in both groups. CONCLUSIONS: Adherence to the employed HAART regimen was poor. Non-IDUs were more adherent than IDUs, but the difference between both groups was small. Side effects and efficacy were similar in IDUs and non-IDUs.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Cooperação do Paciente , Abuso de Substâncias por Via Intravenosa , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Feminino , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/efeitos adversos , Inibidores da Protease de HIV/uso terapêutico , Humanos , Indinavir/administração & dosagem , Indinavir/efeitos adversos , Indinavir/uso terapêutico , Lamivudina/administração & dosagem , Lamivudina/efeitos adversos , Lamivudina/uso terapêutico , Masculino , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/uso terapêutico , Estavudina/administração & dosagem , Estavudina/efeitos adversos , Estavudina/uso terapêutico
12.
Eur J Pharm Sci ; 12(3): 251-9, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11113644

RESUMO

Ganciclovir is one of the most widely used antiviral drug for the treatment of cytomegalovirus retinitis. Due to its short half-life in the vitreous, frequent administrations are necessary to maintain the therapeutic levels. In this context, the aim of this study was to characterise and in vitro evaluate the drug release properties of three different formulations of ganciclovir-loaded albumin nanoparticles. These carriers were prepared by a coacervation method and chemical cross-linking with glutaraldehyde. Depending on the step where the drug and/or cross-linking agent were added three different formulations were obtained, named models A, B and C. For model A nanoparticles, ganciclovir was incubated with the just-formed albumin nanoparticles. For the other two types of nanoparticulate formulations, the drug was added to a solution of albumin (model B) and glutaraldehyde (model C) prior to the formation of the carriers by coacervation. In all cases, the size of the different nanoparticulate formulations was comprised between 200 and 400 nm and the yield ranged from 50%, in model A, to 65% in model B. Concerning the ganciclovir loading, model B nanoparticles offered the higher capacity to carry this antiviral drug (around 30 microg ganciclovir/mg nanoparticle). On the contrary, the drug loading calculated for model A nanoparticles was only 14.6 microg/mg. The in vitro release profiles of the nanoparticles showed a biphasic pattern, with an initial and rapid release, followed by a slower step for up 5 days. This burst effect was especially relevant in model A (around 60% in 1 h), followed by model B (40%) and less important in model C (20%). The addition of trypsin to the release medium did not have a significant influence on the release characteristics. However, the release of the drug was increased in acidic or basic mediums, due to the disruption of the covalent binding between ganciclovir and the protein matrix via glutaraldehyde. This strong linkage was also confirmed by TLC experiences. In summary, a first step of incubation between the drug and the protein, prior to the preparation of nanoparticles, enabled us to obtain albumin carriers able to release ganciclovir in a sustained way.


Assuntos
Antivirais/farmacologia , Ganciclovir/farmacologia , Antivirais/administração & dosagem , Fenômenos Químicos , Físico-Química , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Portadores de Fármacos , Ganciclovir/administração & dosagem , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Microesferas , Tamanho da Partícula , Soroalbumina Bovina
13.
Int J Pharm ; 244(1-2): 59-72, 2002 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-12204565

RESUMO

The goal of this study was the evaluation of albumin nanoparticles as drug delivery systems for antisense oligonucleotides. Bovine serum albumin (BSA) nanoparticles were prepared by a coacervation process. A phosphodiester oligonucleotide was either incorporated into the matrix of the particles by incubation with the albumin prior the coacervation process or adsorbed onto the pre-formed nanoparticles. Incorporated and/or adsorbed oligonucleotide was estimated by capillary electrophoresis and fluorescence spectroscopy. The adsorbed amount of oligonucleotide was dramatically dependent on the pH of the medium. Desorption of the oligonucleotide was also affected by the pH and ionic strength of the medium. This indicated that electrostatic forces play a major role in the interaction between the oligonucleotide and the nanoparticles. When the oligonucleotide was incubated with the albumin prior to nanoparticle formation, the profile of release confirmed that a fraction was incorporated into the matrix and its release was controlled by the albumin degradation. The hybridisation capability of the oligonucleotide in both nanoparticle formulations was retained. However, only the oligonucleotide incorporated into the nanoparticle matrix was protected against enzymatic degradation.


Assuntos
Albuminas/química , Química Farmacêutica , Sistemas de Liberação de Medicamentos , Oligonucleotídeos/administração & dosagem , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Tamanho da Partícula
14.
Community Dent Oral Epidemiol ; 28(1): 10-7, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10634679

RESUMO

OBJECTIVE: To estimate the prevalence of dental stains (DS) in competitive swimmers and quantify the risk of these stains compared with sportsmen in a non-swimmers group in Castellón, Spain. METHODS: Cross-sectional and case-control designs. Between July 1996 and March 1997, 404 subjects, (171 enrolled in two clubs of competitive swimming and 233 sportsmen from two schools), were examined in order to detect and classify yellowish-brown or dark-brown stains on the facial surface of the eight incisors. Participation rates were 88.6% for swimmers, and 95.7% for sportsmen. Mean of participants' age was 12 years, range 7-22 years. Castellón has three public competition swimming pools, two of which are indoors. Two of the pools used chloride products, and the third bromine for the disinfection of water. The recommended hygiene regulations were adhered to. RESULTS: Prevalence of DS was 60.2% in swimmers and 12.9% in sportsmen (P= 0.0001). Risk factors for DS included: use of competition swimming pools, age, gender, years of competition, daily consumption of coffee, red wine, and iron supplement during the last year. Professional dental cleanliness was a protective factor. In a logistic regression analysis, the use of competition swimming pools maintained a high risk of DS, odds ratio (OR)=9.28; 95% confidence interval (CI) 5.21-16.5, adjusted by the other variables. Amongst swimmers, more than 6 h of training a week increased the risk of these stains (OR=3.51; 95% CI 1.35-9.10). CONCLUSION: The study indicated a high risk of DS in competitive swimmers.


Assuntos
Natação , Descoloração de Dente/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Prevalência , Fatores de Risco , Espanha/epidemiologia , Inquéritos e Questionários , Natação/estatística & dados numéricos , População Urbana/estatística & dados numéricos
15.
Arch Bronconeumol ; 37(11): 471-6, 2001 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-11734135

RESUMO

UNLABELLED: Sleep apnea-hypopnea syndrome (SAHS) has been associated with traffic accidents. The aim of this study was to estimate the prevalence of SAHS and analyze risk factors. We studied 163 professional drivers (86.7%) of the 188 employed by 25 participating companies. The subjects completed a questionnaire on SAHS symptoms and risk factors and underwent physical examination and conventional nighttime polysomnographic testing. RESULTS: The prevalence of an apnea-hypopnea index (AHI) ( 5 was 25.2% (95% CI 18.7-32.5) among the drivers. The prevalence of SAHS was 8.6% (95% CI 3.4-12.1). The prevalence increased with age (p = 0.012). Sleepiness while driving or habitual snoring had a sensitivity of 67.5%, specificity of 62.6% and a positive predictive value of 38.6% for detecting SAHS. Logistic regression modelling showed that the risk factors were a body mass index over 29 kg/m2 (OR: 3.56, 95% CI 1.53-8.4) and sleepiness while driving (OR: 3.7, 95% CI: 1.303-10.3). CONCLUSION: These results suggest that detecting SAHS among drivers may be useful for preventing traffic accidents; a questionnaire on SAHS symptoms and objective measures such as polysomnography allow cases to be detected and treated.


Assuntos
Condução de Veículo , Doenças Profissionais/epidemiologia , Síndromes da Apneia do Sono/epidemiologia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Sensibilidade e Especificidade , Inquéritos e Questionários , Fatores de Tempo
16.
Med Clin (Barc) ; 93(17): 641-4, 1989 Nov 25.
Artigo em Espanhol | MEDLINE | ID: mdl-2615544

RESUMO

We report a collective tuna fish poisoning which developed on June 10, 1988, in a staff dining room in Castellón. Twenty-one people were involved (attack rate 42.9%). The major symptoms were diarrhea, abdominal pain, headache, facial flushing and oral burning. The mean duration of the symptoms was 15 hours. The ingestion of tuna fish was significantly associated with the illness (p less than 0.001) when the other foodstuffs were controlled. Tuna fish had been defrosted at room air temperature during 14 hours. The analysis of several foodstuffs (there were no tuna fish remains available) and the food handling staff did not disclose pathogens. We discuss the etiology, pathogenesis, epidemiology and control of this type of food poisoning.


Assuntos
Peixes , Doenças Transmitidas por Alimentos/etiologia , Atum , Animais , Humanos
17.
Gac Sanit ; 12(3): 118-25, 1998.
Artigo em Espanhol | MEDLINE | ID: mdl-9707822

RESUMO

BACKGROUND: Knowledge about salmonellosis risk factors mainly comes from foodborne outbreaks, and we know little about sporadic cases epidemiology. However most of the cases are sporadic, specially children. This study aims to find out some of determinants of these cases. METHODS: A case-control study with incident cases and controls from the same base population (laboratory diagnosed cases). Cases were children 1-7 years old, affected by diarrhea with culture stools positive to Salmonella between december 1994 and december 1995. Controls from the same source, but positive culture to Campylobacter or viruses. We study food and other environmental risk factors. Odds ratio (OR) are calculated adjusted for age, sex, and year period (cool and cold) by logistic regression. RESULTS: Eating minced meat during three days before symptoms, OR 4.07 (1.20-13.8) and OR 5.63 (1.34-23.6); pets, OR 8.27 (1.96-34.9), and antibiotics the week before symptoms, OR 4.75 (0.84-27.0) were epidemiologically associated with salmonellosis diarrhea. CONCLUSIONS: Epidemiology of salmonellosis sporadic cases in children seems different to the foodborne associated cases and is more complex. Minced meat tree days before symptoms, antibiotics the week before symptoms, and pets could be a risk for this kind of cases. Future studies must also take account of this factors.


Assuntos
Infecções por Salmonella/etiologia , Estudos de Casos e Controles , Criança , Pré-Escolar , Diarreia/epidemiologia , Diarreia/microbiologia , Feminino , Humanos , Lactente , Masculino , Razão de Chances , Análise de Regressão , Fatores de Risco , Infecções por Salmonella/epidemiologia , Espanha/epidemiologia
18.
Rev Esp Salud Publica ; 70(1): 63-9, 1996.
Artigo em Espanhol | MEDLINE | ID: mdl-8991703

RESUMO

BACKGROUND: To document an outbreak of Hepatitis B in a gypsy community in the Upper Aragón region, as well as the control measures adopted. METHODS: Documented study of Hepatitis B cases and families, including an epidemiological survey and the determining of hepatitis B viral indicators (MVHB) using immunoenzymatic methods. RESULTS: 84.8% participation (39/45). During the months of February and March 1988, 5 cases of Hepatitis B were detected in a gypsy community in the Upper Aragon region (12.8% attack rate, 5/39), with an average age of 13.0 + 7.3, (4 women and one man). Four of the cases detected had previously undergone tatooing. The fifth case was due to direct transmission from mother to a recently born child. The MVHB study of families showed a further two cases. MVHB rate being 17.9% (7/39). Vaccinations were given to all persons susceptible to the disease. CONCLUSIONS: It is suggested that tatooing could be a significant factor to be considered in relation to the transmission of Hepatitis B in gypsy communities. Due to the high rate of incidence of the disease in this ethnic group, general vaccination is prescribed.


Assuntos
Surtos de Doenças , Hepatite B/epidemiologia , Hepatite B/etiologia , Roma (Grupo Étnico) , Tatuagem/efeitos adversos , Feminino , Hepatite B/prevenção & controle , Vacinas contra Hepatite B/uso terapêutico , Humanos , Incidência , Masculino , Estudos Retrospectivos , Espanha/epidemiologia , Espanha/etnologia
19.
Am J Transplant ; 7(6): 1633-40, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17511688

RESUMO

Heart transplantation (HTx) is a useful therapy for end-stage Chagas cardiomyopathy; however, Chagas reactivation remains a mayor complication. Parasitological methods offer poor diagnostic sensitivity, and use of more sensitive tools such as the Polymerase chain reaction (PCR) is usually necessary. In the present study, reactivation incidence and PCR usefulness for early reactivation diagnosis, as well as for treatment response evaluation during follow-up, were analyzed using Strout parasite detection test, in 10 of 222 consecutive HTx patients suffering Chagas cardiomyopathy. PCR strategies targeted to minicircle sequences (kDNA, detection limit 1 parasite/ 10 mL blood) and miniexon genes (SL-DNA, 200 parasite/10 mL) were performed to compare parasite burdens between samples. No patients received prophylactic antiprotozoal therapy (benznidazole). Five patients (50%) exhibited clinical reactivation within a mean period of 71.6 days; positive Strout results were observed in most cases presenting clinical manifestations. kDNA-PCR was positive 38-85 days before reactivation, whereas SLDNA-PCR became positive only 7-21 days later, revealing post-HTx parasitic load enhancement present prior to clinical reactivation development. Reactivations were successfully treated with benznidazole and generated negative PCR results. Results observed in this study indicate the value of PCR testing for an early diagnosis of Chagas reactivation as well as for monitoring treatment efficacy.


Assuntos
Cardiomiopatia Chagásica/patologia , Cardiomiopatia Chagásica/cirurgia , Doença de Chagas/diagnóstico , Transplante de Coração , Adulto , Animais , Cardiomiopatia Chagásica/diagnóstico , Feminino , Seguimentos , Humanos , Imunossupressores/classificação , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Recidiva , Trypanosoma cruzi/genética , Trypanosoma cruzi/isolamento & purificação
20.
Enferm Infecc Microbiol Clin ; 16(8): 370-3, 1998 Oct.
Artigo em Espanhol | MEDLINE | ID: mdl-9835153

RESUMO

BACKGROUND: Estimation of prevalence of serologic markers of viral hepatitis A, B and C in students and staff of an occupational centre in Castellón (Spain). METHODS: Serologic markers of hepatitis A (IgG anti-HAV) and B (HBsAg, anti-HBe, anti-HBc, anti-HBs) were detected by radioimmunoassay (RIA) and serologic markers of hepatitis C (anti-HCV) by immunoradiometric assay (IRMA). Ninety per cent of students (54/60) and 80% of staff (8/10) participated. RESULTS: The prevalence of IgG anti-HVA was 55.6% in students and 75% in staff, increasing with age. Considering persons not vaccinated against hepatitis B, the prevalence of serologic markers hepatitis B was 18.5% in students, two HBsAg and anti-HBe positive, and nobody in staff. Serologic markers hepatitis B was associated with duration of stay institutions for mentally handicapped. None of the center was positive for anti-HCV. CONCLUSIONS: Viral hepatitis prevalences present notable differences. To maintain a serological surveillance of these diseases is important to control and prevention.


Assuntos
Hepatite A/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Oficinas de Trabalho Protegido , Adolescente , Adulto , Feminino , Pessoal de Saúde , Hepatite A/complicações , Anticorpos Anti-Hepatite A , Anticorpos Anti-Hepatite/sangue , Hepatite B/complicações , Anticorpos Anti-Hepatite B/sangue , Antígenos da Hepatite B/sangue , Hepatite C/complicações , Anticorpos Anti-Hepatite C/sangue , Humanos , Deficiência Intelectual/complicações , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Prevalência , Estudos Soroepidemiológicos , Espanha/epidemiologia
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