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1.
J Prev Alzheimers Dis ; 6(2): 121-134, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30756119

RESUMEN

Alzheimer's disease (AD) is a frequent pathology, with a poor prognosis, for which no curative treatment is available in 2018. AD prevention is an important issue, and is an important research topic. In this manuscript, we have synthesized the literature reviews and meta-analyses relating to modifiable risk factors associated with AD. Smoking, diabetes, high blood pressure, obesity, hypercholesterolemia, physical inactivity, depression, head trauma, heart failure, bleeding and ischemic strokes, sleep apnea syndrome appeared to be associated with an increased risk of AD. In addition to these well-known associations, we highlight here the existence of associated factors less described: hyperhomocysteinemia, hearing loss, essential tremor, occupational exposure to magnetic fields. On the contrary, some oral antidiabetic drugs, education and intellectual activity, a Mediterranean-type diet or using Healthy Diet Indicator, consumption of unsaturated fatty acids seemed to have a protective effect. Better knowledge of risk factors for AD allows for better identification of patients at risk. This may contribute to the emergence of prevention policies to delay or prevent the onset of AD.


Asunto(s)
Enfermedad de Alzheimer/epidemiología , Literatura de Revisión como Asunto , Factores de Riesgo , Traumatismos Craneocerebrales/epidemiología , Depresión/epidemiología , Diabetes Mellitus/epidemiología , Dieta Mediterránea/estadística & datos numéricos , Grasas Insaturadas en la Dieta , Escolaridad , Temblor Esencial/epidemiología , Pérdida Auditiva/epidemiología , Insuficiencia Cardíaca/epidemiología , Humanos , Hiperhomocisteinemia/epidemiología , Hipertensión/epidemiología , Hipoglucemiantes/uso terapéutico , Campos Magnéticos , Metaanálisis como Asunto , Obesidad/epidemiología , Exposición Profesional/estadística & datos numéricos , Factores Protectores , Conducta Sedentaria , Síndromes de la Apnea del Sueño/epidemiología , Fumar/epidemiología , Accidente Cerebrovascular/epidemiología
2.
Rev Med Interne ; 36(11): 728-37, 2015 Nov.
Artículo en Francés | MEDLINE | ID: mdl-26343874

RESUMEN

INTRODUCTION: The main objective of the study was to assess the adequacy of antibiotic therapy for urinary tract infections (UTI) in a French hospital medical department. The secondary objective was to identify factors associated with inadequacy of the antibiotic therapy. METHODS: A retrospective single centre cohort study was performed in the Post-Emergency Medicine Department (PEMD) of the university hospital of Lille. All patients presenting with an UTI from May 2012 to April 2014 were included. Adequacy of antibiotic therapy was assessed with reference to local guidelines. Factors associated with inadequacy of antibiotic prescription were determined using a multivariate logistic regression model. RESULTS: Two hundred and twenty-eight patients were included. The antibiotic prescription was fully adequate in 173 patients (76%) with appropriate use of a single or a combination antibiotic therapy in 96%, appropriate drug in 80%, appropriate dosage in 89% and appropriate route of administration in 95%. The risk for antibiotic inadequacy was significantly higher in patients with cystitis than in those with pyelonephritis (OR 12.01; 95% CI 4.17-34.65), when antibiotics were prescribed in the Emergency Department (OR 6.84; 95% CI 2.29-20.47) or before hospital admission (OR 382.46; 95% CI 19.61≥999.99) compared to when antibiotics were first administered in the PEMD, and in patients with severe UTI (OR 19.55; 95% CI 2.79-137.01). CONCLUSION: Adequacy of antibiotic therapy for UTI is relatively high in our study, reflecting the effective dissemination of antibiotic guidelines. However, antibiotic therapy is still inappropriate in cystitis, severe UTI and in case of prescription before the admission in the PEMD.


Asunto(s)
Antibacterianos/uso terapéutico , Adhesión a Directriz , Prescripción Inadecuada/estadística & datos numéricos , Guías de Práctica Clínica como Asunto , Infecciones Urinarias/tratamiento farmacológico , Anciano , Estudios de Cohortes , Cistitis/tratamiento farmacológico , Servicio de Urgencia en Hospital , Femenino , Francia , Hospitales Universitarios , Humanos , Masculino , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
3.
Clin Exp Dermatol ; 40(4): 356-60, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25623526

RESUMEN

BACKGROUND: Ageing is a determining factor in skin cancer, but the incidence and prevalence of skin cancer in elderly patients are not known. AIM: To determine the prevalence of skin cancers in elderly patients and to assess their associated geriatric syndromes. METHODS: Between January and April 2013, all consecutive incident patients hospitalized in the Acute Geriatric Unit of Lille University Hospital underwent a geriatric assessment and a systematic dermatological examination. A biopsy was taken whenever there was any lesion with suspicion of malignancy. RESULTS: In total, 204 patients (mean age 85.4 years) were included, and 16 cutaneous biopsies were taken from 15 patients. Histological examination confirmed skin cancer in 11 biopsies from 10 patients: 9 basal cell carcinomas, 1 squamous cell carcinoma (SCC) and 1 malignant lentigo. The prevalence of skin cancer was 4.9%. The geriatric assessment revealed severe geriatric syndromes in the 10 patients with skin cancer: severe dependence (8/10), possible cognitive impairment (10/10), and moderate or severe malnutrition (5/10). CONCLUSIONS: The prevalence of skin cancer is high in frail elderly patients. The association of severe geriatric syndromes suggests that close collaboration between geriatricians and dermatologists is essential to optimize the treatment of skin carcinoma in elderly patients.


Asunto(s)
Neoplasias Cutáneas/epidemiología , Anciano , Anciano de 80 o más Años , Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Femenino , Anciano Frágil , Evaluación Geriátrica/métodos , Humanos , Peca Melanótica de Hutchinson/epidemiología , Masculino , Prevalencia , Factores de Riesgo
4.
J Nutr Health Aging ; 13(6): 503-19, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19536419

RESUMEN

Under the auspices of the Societe Francaise de Geriatrie et Gerontologie, a multi-disciplinary group of specialists in geriatrics, neurology, epidemiology, psychiatry, neuroradiology and nuclear medicine met with the aim of drawing up references on the methods for diagnosing and treating mild Alzheimer's disease. The critical analysis of international literature, conducted by Professor Bruno Vellas for the scientific committee, has served to support study of the latest knowledge in 2008. The multi-disciplinary group met on 14 and 15 May 2008 in order to set out the questions that this study must answer and to allocate draft studies. Thus, it has been possible to conduct a study focused on mild Alzheimer's disease, giving particular attention to diagnostic procedure, specific methods of treatment and the benefits of making a diagnosis.


Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/terapia , Tamizaje Masivo , Anciano , Enfermedad de Alzheimer/psicología , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Cognición , Progresión de la Enfermedad , Evaluación Geriátrica/métodos , Humanos , Tamizaje Masivo/métodos , Trastornos Mentales/diagnóstico , Índice de Severidad de la Enfermedad
5.
Rev Mal Respir ; 24(6): 703-23, 2007 Jun.
Artículo en Francés | MEDLINE | ID: mdl-17632431

RESUMEN

INTRODUCTION: In France, the average age for the diagnosis of bronchial carcinoma is 64. It is 76 in the population of over 70. In fact, its incidence increases with age linked intrinsic risk of developing a cancer and with general ageing of the population. Diagnosis tools are the same for elderlies than for younger patients, and positive diagnosis mainly depends on fibreoptic bronchoscopy, complications of which being comparable to those observed in younger patients. STATE OF THE ART: The assessment of dissemination has been modified in recent years by the availability of PET scanning which is increasingly becoming the examination of choice for preventing unnecessary surgical intervention, a fortiori in elderly subjects. Cerebral imaging by tomodensitometry and nuclear magnetic resonance should systematically be obtained before proposing chirurgical treatment. An assessment of the general state of health of the elderly subject is an essential step before the therapeutic decision is made. This depends on the concept of geriatric evaluation: Geriatric Multidimensional Assessment, and the Comprehensive Geriatric Assessment which concerns overall competence of the elderly. PERSPECTIVES: This is a global approach that allows precise definition and ranking of the patient's problems and their impact on daily life and social environment. Certain geriatric variables (IADL, BADL, MMSE, IMC etc) may be predictive of survival rates after chemotherapy or the incidence of complications following thoracic surgery. The main therapeutic principles for the management of bronchial carcinoma are applicable to the elderly subject; long term survival without relapse after surgical resection is independent of age. Whether the oncological strategy is curative or palliative, the elderly patient with bronchial carcinoma should receive supportive treatments. They should be integrated into a palliative programme if such is the case. In fact, age alone is not a factor that should detract from optimal oncological management. CONCLUSIONS: The development of an individual management programme for an elderly patient suffering from bronchial carcinoma should be based on the combination of oncological investigation and comprehensive geriatric assessment.


Asunto(s)
Neoplasias Pulmonares/fisiopatología , Factores de Edad , Anciano , Anciano de 80 o más Años , Diagnóstico por Imagen , Evaluación Geriátrica , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , Cuidados Paliativos , Planificación de Atención al Paciente
6.
Rev Med Interne ; 22(2): 127-31, 2001 Feb.
Artículo en Francés | MEDLINE | ID: mdl-11234670

RESUMEN

PURPOSE: To determine aged-related variations in clinical and biological presentation and outcome in Wegener's granulomatosis. METHODS: In a retrospective cohort study of 35 patients with a diagnosis of Wegener's granulomatosis, 24 patients (69%) younger than 60 years of age and 11 (31%) aged 60 years or older were compared for clinical and biological characteristics. RESULTS: Clinical presentation was the same in the two groups; lymphopenia was more common in the elderly group (P > 0.05). Despite a similar treatment regime, outcome was significantly worse for the elderly group (> or = 60 years), with a mortality rate of 36% versus 8% in the control group. Mortality was essentially due to delayed infectious complications, raising the problem of a less intensive immunosuppressive treatment after remission.


Asunto(s)
Granulomatosis con Poliangitis/diagnóstico , Granulomatosis con Poliangitis/tratamiento farmacológico , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Femenino , Granulomatosis con Poliangitis/complicaciones , Granulomatosis con Poliangitis/mortalidad , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Infecciones/etiología , Masculino , Persona de Mediana Edad , Inducción de Remisión/métodos , Estudios Retrospectivos , Resultado del Tratamiento
7.
Rev Med Interne ; 22(1): 11-9, 2001 Jan.
Artículo en Francés | MEDLINE | ID: mdl-11218294

RESUMEN

PURPOSE: In case of unexplained weight loss, chest X-ray, abdominal ultrasonography and gastroscopy are usually recommended. However, gastroscopy is not usually performed in elderly patients. METHODS: We evaluated 77 patients (mean age: 80 +/- 8 years) hospitalized in our geriatric unit between January 1995 and May 1997 for unexplained weight loss. All patients underwent chest X-ray, abdominal ultrasonography and gastroscopy. RESULTS: These investigations led to diagnosis in respectively 17, 15 and 46 patients. The etiology of weight loss was unique in 47 patients, while in 30 other patients at least two or three causes could be described. Gastroscopy appeared to be the most useful test, as it allowed description of eight cases of cancer, 29 cases of peptic ulcer, two cases of candidosis, and one case of actinomycosis in patients who did not present any clinical sign. CONCLUSION: Sixty-five patients were followed-up for a mean period of 13 +/- 21 month; 33 patients died. The condition of 23 patients improved either slightly or definitely. Simple investigations led to diagnosis in 95% of the cases. However, 42% of the patients died within 3 months. Gastroscopy appears to be the most valuable test, leading to diagnosis in more than half of the cases. With adapted treatment, the condition of 75% of the patients with gastro-intestinal lesions improved.


Asunto(s)
Gastroscopía/métodos , Gastropatías/diagnóstico , Pérdida de Peso , Abdomen/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Geriatría , Humanos , Masculino , Pronóstico , Radiografía Torácica , Ultrasonografía
8.
Antimicrob Agents Chemother ; 45(2): 553-62, 2001 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-11158754

RESUMEN

The present study compared the abilities of different lipid carriers of amphotericin B (AMB) to activate murine peritoneal macrophages, as assessed by their capacities to produce nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha). Although AMB alone did not induce NO production, synergy was observed with gamma interferon but not with lipopolysaccharide. This synergy could not be explained by the mobilization of the nuclear activation factor NF-kappaB by AMB. On the other hand, AMB induced TNF-alpha production without a costimulator and no synergy was observed. Anti-TNF-alpha antibodies did not influence NO production, and an inhibitor of NO synthase did not affect TNF-alpha production, indicating that the production of one of these effector molecules was independent of that of the other. The incorporation of AMB into lipid carriers reduced NO and TNF-alpha production with all formulations but more so with liposomes than with lipid complexes. NO production was correlated with the induction of NO synthase II, revealed by Western blotting. The extent of association of AMB with macrophages depended on the formulation, especially on the AMB/lipids ratio: the higher the ratio was, the greater the AMB association with macrophages. However, there was no clear correlation between AMB association with macrophages, whether internalized or bound to the membrane, and immunostimulating effects. These results may explain the reduced toxicities of lipid-based formulations of AMB.


Asunto(s)
Adyuvantes Inmunológicos/farmacología , Anfotericina B/farmacología , Antifúngicos/farmacología , Macrófagos/metabolismo , Óxido Nítrico Sintasa/biosíntesis , Factor de Necrosis Tumoral alfa/biosíntesis , Adyuvantes Inmunológicos/administración & dosificación , Anfotericina B/administración & dosificación , Anfotericina B/metabolismo , Antifúngicos/administración & dosificación , Antifúngicos/metabolismo , Western Blotting , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Portadores de Fármacos , Humanos , Interferón gamma/farmacología , Liposomas , Macrófagos/efectos de los fármacos , Macrófagos/enzimología , FN-kappa B/metabolismo , Nitritos/metabolismo , Biosíntesis de Proteínas
9.
J Gerontol A Biol Sci Med Sci ; 55(9): M535-40, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10995052

RESUMEN

BACKGROUND: Postprandial hypotension (PPH) is increasingly recognized as a common cause of falls and syncope in elderly persons. Noninvasive ambulatory blood pressure monitoring (ABPM) has been recommended for detecting PPH. This study investigates postprandial blood pressure (BP) changes by means of ABPM in elderly patients experiencing falls or syncopes. METHODS: Twenty-four-hour ABPM was performed in 156 inpatients (111 women, mean age 80.4 +/- 8.1 years). Among them, 45 had been admitted for falls and 75 for syncope; 36 with no history of falls or syncope served as controls. Postprandial change in systolic blood pressure (deltaSBP) was calculated by subtracting the mean SBP within the 2 hours following the meal from the mean SBP within the 2 hours preceding the meal. PPH was defined by a deltaSBP > or = 20 mm Hg. RESULTS: For the entire group, mean SBP decreased after the three meals. On average, the decline in SBP was greater after breakfast than after lunch or dinner, and the number of patients experiencing PPH was greater after breakfast. Average maximal deltaSBP was significantly larger in the syncope group than in the other groups ( p < .05). Moreover, the number of patients experiencing PPH was significantly higher in the syncope/fall group than in the control group (23% vs 9%; p = .03). Compared with patients without PPH, patients with PPH were more likely to have a history of diabetes mellitus (p < .01) or to use more than three different drugs daily ( p = .04), and they showed greater daytime SBP variability (p < .0001). Furthermore, there was a strong positive correlation between preprandial SBP and deltaSBP after breakfast. CONCLUSIONS: About one out of four elderly patients with falls or syncope experiences PPH, usually after breakfast. Postprandial decline in BP contributes to BP variability. deltaSBP and preprandial SBP are positively correlated.


Asunto(s)
Accidentes por Caídas , Presión Sanguínea/fisiología , Ingestión de Alimentos/fisiología , Hipotensión/complicaciones , Monitoreo Ambulatorio , Síncope/etiología , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Ritmo Circadiano , Complicaciones de la Diabetes , Femenino , Humanos , Hipotensión/fisiopatología , Masculino , Persona de Mediana Edad , Polifarmacia , Síncope/fisiopatología , Sístole , Factores de Tiempo
10.
Ann Med Interne (Paris) ; 151(4): 243-7, 2000 Jun.
Artículo en Francés | MEDLINE | ID: mdl-10922950

RESUMEN

Actinomyces are Gram positive, anaerobic, filamentous bacteria, saprophytes of the oral cavity and intestinal tract of humans. They rarely cause chronic suppurative infections. Abdominal abscess can masquerade as a malignant process and lead to a surgical intervention with resection. We report three patients with abdominal actinomycosis; the first affected the liver with a favorable outcome on medical treatment, the second of abdomino-pelvic localisation was related to an intra-uterine device and the last affecting the transverse colon simulated a malignant process and required an hemicolectomy. These observations illustrates the difficulties of the diagnosis of this rare and unrecognized disease.


Asunto(s)
Absceso Abdominal/diagnóstico , Absceso Abdominal/terapia , Actinomicosis/diagnóstico , Actinomicosis/terapia , Enfermedades del Colon/diagnóstico , Enfermedades del Colon/terapia , Absceso Hepático/diagnóstico , Absceso Hepático/terapia , Absceso Abdominal/etiología , Actinomicosis/etiología , Adulto , Biopsia , Colectomía , Enfermedades del Colon/etiología , Terapia Combinada , Femenino , Humanos , Dispositivos Intrauterinos/efectos adversos , Absceso Hepático/etiología , Masculino , Persona de Mediana Edad , Penicilina G/uso terapéutico , Penicilinas/uso terapéutico , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
11.
Drug Dev Ind Pharm ; 25(2): 175-86, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10065351

RESUMEN

To tattoo human breast cancer prior to chemotherapy, radiotherapy, or surgery, thus allowing a better localization of the remaining tumor by the surgeon, we developed a formulation containing 10% charcoal suspended in water for parenteral preparations. The present study concerns a new step in the development of the charcoal suspension. We sought to determine whether the addition of various excipients could improve the formulation properties and affect the labeling of tumor by the suspension. We have tested surfactants (egg lecithin, polysorbate 80, Cremophor EL, and Pluronic F68), isotonisants (sugars such as glucose and mannitol), polysaccharides (dextrans 20 and 40), and Cabosil, a pyrogenated silica. Except for glucose and mannitol, which were added at a 5% concentration, the other excipients were added at a 0.1% concentration, they were dissolved in water for parenteral injection and sterilized at 120 degrees C for 20 min. We then measured diffusion in vivo in mammary tumor. In vivo, when injected intratumorally in mice, a greater diffusion of charcoal particles was noted within the tumor (in the case of egg lecithin, polysorbate 80, dextran 20 and 40, and glucose) and sometimes in some organs (e.g., Cremophor EL and mannitol). Pluronic F68 slightly improved the stability of the suspension and did not lead to marked diffusion at the injection site, but it showed slight toxicity and cannot be used in the formulation. We concluded that the best formulation was an aqueous 10% micronized peat charcoal suspension.


Asunto(s)
Adenocarcinoma/cirugía , Carbón Orgánico/administración & dosificación , Sistemas de Liberación de Medicamentos , Excipientes , Neoplasias Mamarias Experimentales/cirugía , Animales , Carbón Orgánico/farmacocinética , Carbón Orgánico/toxicidad , Química Farmacéutica , Emulsiones , Femenino , Concentración de Iones de Hidrógeno , Ratones , Ratones Endogámicos C3H , Reología , Suspensiones , Distribución Tisular
12.
Int J Radiat Oncol Biol Phys ; 42(1): 179-84, 1998 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-9747836

RESUMEN

PURPOSE: To develop an experimental model of acute encephalopathy following total body irradiation in rats and to define the therapeutic effect of liposome-entrapped Cu/Zn superoxide dismutase. METHODS AND MATERIALS: A total of 120 4-month-old rats received 4.5 Gy total body irradiation (TBI) while 120 rats received sham irradiation. A behavioral study based on a conditioning test of negative reinforcement, the one-way avoidance test, was performed 5 hours before irradiation and repeated the following days. Subcutaneous treatment was started 1 hour after irradiation and repeated daily for 2 weeks. In both the irradiated and sham group, three subgroups were defined according to the treatment received: liposome-entrapped Cu/Zn superoxide dismutase (0.5 mg/kg), liposomes only, normal saline. RESULTS: This work comprised two consecutive studies. In study A (90 rats) the one-way avoidance test was administered daily from day 0 to day 4 with a recall session at day 14. In study B (validation phase in 150 rats) the behavioral test was performed only from day 0 to day 6. Before irradiation, all rats showed a similar behavioral response. Study A (6 groups of 15 rats): Following TBI, irradiated rats treated with liposomes only or saline demonstrated a significant delay in learning the one-way avoidance test in comparison with sham-irradiated rats (0.05 < p <0.001 depending upon the day of evaluation and the subgroup type). In contrast, irradiated rats treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from sham-irradiated rats. Study B (6 groups of 25 rats): The results were the same as those in study A, demonstrating a significant delay in the learning of the test in the liposome and saline-treated irradiated rats in comparison with sham-irradiated rats (0.02 < p < 0.001). The irradiated rats, treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from the sham-irradiated controls. CONCLUSION: This study indicates that a relatively low dose of total body irradiation induces a substantial acute learning dysfunction in the rat. This effect is prevented by the administration of liposome-entrapped Cu/Zn superoxide dismutase.


Asunto(s)
Reacción de Prevención/efectos de la radiación , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/etiología , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Superóxido Dismutasa/uso terapéutico , Irradiación Corporal Total/efectos adversos , Animales , Condicionamiento Psicológico , Modelos Animales de Enfermedad , Portadores de Fármacos , Liposomas , Masculino , Ratas , Ratas Wistar
14.
Pharm Res ; 15(7): 1051-5, 1998 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-9688059

RESUMEN

PURPOSE: The aim of this study was to prepare and characterize nanoparticulate systems constituted of poly(isobutylcyanoacrylate) and cyclodextrins and intended for increasing the loading of the particles with lipophilic substances. Progesterone was used as a model substance. METHODS: Nanoparticles were prepared by polymerization of isobutylcyanoacrylate in presence of cyclodextrins or progesterone/ hydroxypropyl-beta-cyclodextrin complex. Particle size, zeta potential, cyclodextrin and progesterone loading of the particles were determined. RESULTS: Nanoparticles could be easily prepared in presence of cyclodextrins. An increase in hydroxypropyl-beta-cyclodextrin concentration resulted in small nanoparticles (less than 50 nm). It was found that large amounts of cyclodextrins remained associated to the particles, resulting in a 50 fold increase in progesterone loading compared to nanoparticles prepared in absence of cyclodextrins. CONCLUSIONS: The poly(isobutylcyanoacrylate)cyclodextrin nanoparticles were characterized by the presence of many lipophilic sites belonging to the cyclodextrins which were firmly anchored to the structure of the particles. Therefore, this new type of nanoparticles offers probably an opportunity for increasing the loading of nanoparticles with various lipophilic drugs.


Asunto(s)
Bucrilato/química , Ciclodextrinas/química , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Portadores de Fármacos , Tamaño de la Partícula , Progesterona/administración & dosificación , Tensoactivos/química
15.
Pharm Dev Technol ; 3(1): 85-94, 1998 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9532603

RESUMEN

The aim of this work was to evaluate the loading capacity and the association characteristics of the hydrophobic drug progesterone on amphiphilic cyclodextrin nanospheres prepared by the nanoprecipitation method. The colloidal suspensions were prepared in the presence or absence of two different surfactants, Pluronic F68 and Tween 80. The physicochemical characteristics of the nanospheres were assessed using a nanosizer, zetameter, and transmission electron microscope. The physical state of the drug was verified using differential scanning calorimetry (DSC) and x-ray diffraction (XRD) methods. The in vitro progesterone release was investigated at 37 degrees C after dilution of the suspensions in sink conditions. Nanospheres with a mean diameter from 100 to 300 nm and a low degree of polydispersity were prepared from amphiphilic hexanoyl-gamma-cyclodextrin. The progesterone loading capacity was not affected by the formulation parameters tested. The DSC and XRD studies demonstrated the absence of the crystalline domains of progesterone in loaded nanospheres. The DSC studies also demonstrated the presence of interactions between the drug and carrier. The release of the drug from the carrier was extremely rapid and was governed by a partition phenomenon that depends only on the solubility of the drug in the release medium. From these results, we concluded that with this method, the progesterone is molecularly associated at the surface of the cyclodextrin nanospheres, probably through hydrophobic interactions in specific sites. The release profiles obtained can be of value when an improvement in the bioavailability of the drug is desired.


Asunto(s)
Ciclodextrinas/química , Microesferas , Progesterona/administración & dosificación , Rastreo Diferencial de Calorimetría , Portadores de Fármacos , Estudios de Evaluación como Asunto , Microscopía Electrónica , Tamaño de la Partícula , Poloxaleno , Polisorbatos , Progesterona/farmacocinética , Tensoactivos , Difracción de Rayos X
16.
Ann Pharm Fr ; 56(6): 256-63, 1998.
Artículo en Francés | MEDLINE | ID: mdl-9872012

RESUMEN

The aim of the work was to develop small microspheres made from a biodegradable polymer, poly(lactide-co-glycolide), in order to entrap small peptides. Microspheres prepared by a water-in-oil-in-water emulsion solvent evaporation technique displayed a mean diameter below than 10 microns and showed high encapsulation efficiency of a 33 amino acid peptide (V3 BRU). In vitro release kinetics studies showed that such microparticles could be employed for both oral immunization and controlled release. The encapsulation of a seven aminoacid peptide in the same conditions, led to a very low encapsulation efficiency. In order to increase the entrapment efficiency, two strategies were adopted: taking into account the solubility of pBC 264 at different pH, a pH gradient was created to prevent the leakage of the encapsulated peptide into the outer aqueous phase. The inner aqueous phase was maintained at basic pH where the peptide was soluble, while the external aqueous phase was acidic: ovalbumin was added during preparation to stabilize the inner emulsion. These two strategies allowed to increase significantly the encapsulation rate of pBC 264. Nevertheless, the in vitro release kinetics of the peptide were strongly influenced by the presence of ovalbumin which seems to form pores in the microsphere structure (80% of the total peptide content was released after 30 minutes). By contrast, when ovalbumin was replaced by Pluronic F 68 microspheres did not have pores, thus the release profile and the extent of the burst were much smaller. When microspheres were stereotactically implanted in the rat brain, in vivo release profiles were in good agreement with the release observed in vitro. In conclusion, these microspheres are well suited for the slow delivery of neuropeptides in the brain, a feature expected to facilitate the study of long term effects of these compounds.


Asunto(s)
Ácido Láctico , Péptidos/administración & dosificación , Ácido Poliglicólico , Polímeros , Animales , Cápsulas , Microesferas , Ratas
17.
J Biomed Mater Res ; 34(3): 317-26, 1997 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-9086401

RESUMEN

To develop rapidly biodegradable "stealth" nanoparticles, a physicochemical investigation was done on the formation of PEG-coated poly(isobutyl 2-cyanoacrylate) (PIBCA) nanoparticles. In particular, this study focused on the effect of polymerization conditions on particle size and surface properties, such as charge and hydrophilicity. Among the parameters involved, the pH of the polymerization medium was found to be a key to control the preparation of PEG-coated nanoparticles. Currently, poly(alkylcyanoacrylate) (PACA) nanoparticles are prepared in H2O at pH 2.5, the most appropriate for producing nanoparticles with a mean diameter of 200 nm and an unimodal size distribution. The presence of PEG in the polymerization medium was shown to affect particles formation: only a pH value < 1.5 led to the formation of colloidal nanoparticles, and slight pH variations dramatically affected particle size and PEG association. Polymer chemistry investigations and chemical determination of PEG strongly suggest that PEG associated with nanoparticles was well copolymerized with PIBCA.


Asunto(s)
Materiales Biocompatibles/síntesis química , Cianoacrilatos/síntesis química , Polímeros/síntesis química , Materiales Biocompatibles/química , Materiales Biocompatibles/aislamiento & purificación , Rastreo Diferencial de Calorimetría , Fenómenos Químicos , Química Física , Coloides , Cianoacrilatos/química , Cianoacrilatos/aislamiento & purificación , Portadores de Fármacos/síntesis química , Portadores de Fármacos/química , Portadores de Fármacos/aislamiento & purificación , Estabilidad de Medicamentos , Enbucrilato , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Ensayo de Materiales , Tamaño de la Partícula , Polietilenglicoles/química , Polímeros/química , Polímeros/aislamiento & purificación , Solubilidad , Espectroscopía Infrarroja por Transformada de Fourier , Propiedades de Superficie
18.
Pharm Res ; 14(2): 218-23, 1997 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9090713

RESUMEN

PURPOSE: We developed a charcoal suspension formulation to be injected intratumorally so that human breast cancers can be tatooed prior to chemotherapy. This deposit is intended to guide the surgeon at the time of the biopsy and resection, especially when the tumor nodule is not visible. The stain should remain in the tumor as long as the patient is on chemotherapy and should be harmless. METHODS: We studied on the effect on the nature of the charcoal, its granulometric profile, and its concentration. We then measured diffusion in vitro, in gel, and in vivo in experimental tumors. RESULTS: The formulation selected was prepared with a peal charcoal suspension in water for parenteral injections, with 50% of the particles measuring on average between 2 and 5 microns. The finest particles (< 2 microns) seem to produce the greatest in vitro diffusion and are more readily phagocyted by macrophages and thus eliminated from the tumor by those cells. CONCLUSIONS: This charcoal suspension has satisfactory formulation characteristics and diffuses the least, be it in vitro or in vivo, mainly due to the granulometric distribution of the suspension.


Asunto(s)
Carbón Orgánico/química , Neoplasias Mamarias Experimentales/diagnóstico , Animales , Difusión , Relación Dosis-Respuesta a Droga , Femenino , Inyecciones Intralesiones , Neoplasias Mamarias Experimentales/patología , Ratones , Ratones Endogámicos C3H , Trasplante de Neoplasias , Tamaño de la Partícula , Suspensiones
19.
Br J Cancer ; 76(2): 198-205, 1997.
Artículo en Inglés | MEDLINE | ID: mdl-9231919

RESUMEN

Polyalkylcyanoacrylate (PACA) nanoparticles loaded with doxorubicin allowed multidrug resistance to be overcome in vitro. However, increased cytotoxicity is not always correlated with an increased level of intracellular drug. Although we have previously shown that PACA nanoparticles are not endocytosed by tumour cells, we report here that a direct interaction between nanoparticles and cells is a necessary requirement for overcoming resistance. In addition, the results showed that the degradation products of PACA (mainly polycyanoacrylic acid) in the presence of doxorubicin are able to increase both accumulation and cytotoxicity, thus suggesting the formation of a doxorubicin-polycyanoacrylic acid ion pair. It is therefore concluded that resistance is overcome as a result of both the adsorption of nanoparticles to the cell surface and increased doxorubicin diffusion by the accumulation of an ion pair at the plasma membrane.


Asunto(s)
Antibióticos Antineoplásicos/metabolismo , Cianoacrilatos/farmacología , Doxorrubicina/metabolismo , Resistencia a Múltiples Medicamentos , Leucemia P388/metabolismo , Polímeros/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos , Resistencia a Antineoplásicos , Enbucrilato , Leucemia P388/tratamiento farmacológico , Microesferas , Espectrometría Raman , Células Tumorales Cultivadas/efectos de los fármacos
20.
Int J Androl ; 18(6): 287-94, 1995 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8719844

RESUMEN

The effect of co-incubating human spermatozoa with 8 mmol/L dilauroylphosphatidylcholine (PC12) liposomes containing 6 mmol/L adenosine 5'-triphosphate (LATP) was assessed by CASA and compared to that obtained with blank PC12 liposomes (LB). The aim of this study was to investigate if such treatments can improve sperm movement and sustain sperm motility over time. Significant and similar increases in straight-line velocity and linearity of sperm movement in B2 capacitating medium (both p < 0.01) were obtained with LB and LATP treatments (final concentration: 0.38 mmol/L PC12 and 0.5 mmol/L ATP) while in Tyrode's medium supplemented with 10 mg/mL BSA, these movement parameters were increased significantly only in sperm aliquots treated with LATP. Furthermore, after incubation for 0.5 h in Tyrode's, a bioluminescence assay of intracellular ATP indicated no significant change in ATP concentration for LATP-treated spermatozoa while the ATP content of control and LB-treated spermatozoa decreased significantly during the same period (both p < 0.05). The effect of liposomes on the acrosome reaction was also investigated jointly with CASA. These experiments were performed by fluorescence microscopy, using PSA-FITC and the supravital stain Hoechst 33258. After a precapacitation period of 3 h in BWW medium the spermatozoa were incubated for 1 h with LATP, LB, LB+free ATP and free ATP alone (final concentration 0.5 mmol/L ATP). Under these conditions the percentage of acrosome-reacted spermatozoa was increased similarly after LATP and LB treatments compared to control (respectively from 4.9 to 12%, p < 0.01 and 4.9 to 11.3%, p < 0.05) but the percentage of true acrosome-reacted spermatozoa, and the values for all movement characteristics (except percentage motility) were increased significantly only with LATP treatment. The results indicate the potential of PC12 vesicles for introducing highly hydrophilic compounds into spermatozoa, as well as for modulating membrane structures and functions required for fertilization.


Asunto(s)
Acrosoma/fisiología , Adenosina Trifosfato/farmacología , Motilidad Espermática/efectos de los fármacos , Interacciones Espermatozoide-Óvulo , Acrosoma/efectos de los fármacos , Adenosina Trifosfato/administración & dosificación , Portadores de Fármacos , Femenino , Humanos , Cinética , Liposomas , Masculino , Fosfatidilcolinas , Semen/fisiología , Interacciones Espermatozoide-Óvulo/efectos de los fármacos , Factores de Tiempo
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