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1.
J Stomatol Oral Maxillofac Surg ; 123(1): 16-21, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33596475

RESUMO

During the 2020 coronavirus pandemic, a lockdown was imposed in France during the first wave. An apparent decrease in incidence of cellulitis of odontogenic origin was noticed then. This study aimed to compare the incidence of cellulitis during this extraordinary period with the same period in 2018 and 2019, based on retrospective multicentric data. All maxillofacial surgery departments in French public hospitals were contacted. Responders were asked to include all patients admitted for the surgical drainage of a head and neck abscess of odontogenic origin during the first 2020 lockdown period, and in a similar time frame in 2018 and 2019 (control group), based on screening the French diagnostic and therapeutic classification of medical acts. We report a 44% significant nationwide decrease in the incidence of admissions for cellulitis. There were 187 patients in 2020 for 334 and 333 patients in 2018/2019 respectively. The reasons to explain this finding are hypothetical (organizational reasons leading to earlier management, patients' fear to seek for medical management, usual excess in surgical indications or concomitant decrease of non-steroidal anti-inflammatory drugs delivery). Whatever the explanation, it would be of great interest to find it out in order to improve the prevention of cellulitis.


Assuntos
COVID-19 , Celulite (Flegmão) , Celulite (Flegmão)/diagnóstico , Celulite (Flegmão)/epidemiologia , Celulite (Flegmão)/etiologia , Controle de Doenças Transmissíveis , Humanos , Estudos Retrospectivos , SARS-CoV-2
2.
J Stomatol Oral Maxillofac Surg ; 120(2): 167-171, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30718213

RESUMO

It is recognized that the mandibular reconstruction with free flap allows for both functional and aesthetic restoration. The flap must be used for reconstruction of a smooth lower mandibular contour and also the alveolar bone to allow dental rehabilitation. The double-barrel fibula free flap does respond well to these imperatives, but it increases risk of vascular complications. To overcome these risks, we propose a single-barrel fibula free flap, positioned at the alveolar level and a customized 3D implant, designed by computer-assisted surgery, at the basilar level. The interest of the single-barrel fibula associated with a customized 3D implant compared to the double-barrel fibula free flap is twofold: it decreases the vascular risks associated with the plication of the second pedicle and allows patients to have a pedicle of greater length. It also allows them to have a good cortical bone placed in the alveolar bone to rehabilitate the mastication function.


Assuntos
Neoplasias Mandibulares , Cirurgia Assistida por Computador , Transplante Ósseo , Estética Dentária , Fíbula , Humanos
3.
J Stomatol Oral Maxillofac Surg ; 120(2): 95-98, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30513388

RESUMO

New technologies have over the past forty years become widespread across all domains of basic and applied research particularly in health-related fields. Telemedicine is a form of remote medical practice using information and communication technologies. It connects one or more health professionals with other health professionals or with patients. Within the framework of emergencies in maxillofacial surgery, requests received for specialist advice often pertain to procedures to be followed for facial wounds, bites, burns, maxillofacial bone trauma or facial cellulitis. These requests for specialist advice were previously made by phone between emergency physicians and maxillofacial specialists, with exchange of patient photos by text messaging, which raised security issues. We collaborated with the Telehealth Normandy Health Cooperation Group (GCS TSBN) for the implementation of a mobile application using the "Therap-e" telemedicine platform. This platform links together websites and remote health professionals via the Internet. Physicians communicate over a mobile network or from a health institution, in online or offline mode, synchronously or asynchronously, using any medium (tablet, PC, Mac, smartphone). This scheme both ensures secure transmission of personal and clinical data (especially facial photographs) and records specialist advice in patient medical records. The purpose of tele-expertise applications in an emergency context is to provide a solution to the demographic problems facing healthcare professionals and to rise to the growing challenges surrounding quality and security issues.


Assuntos
Traumatismos Maxilofaciais , Aplicativos Móveis , Smartphone , Telemedicina , Serviço Hospitalar de Emergência , Humanos
4.
J Visc Surg ; 155(4): 343-344, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30017421
5.
J Stomatol Oral Maxillofac Surg ; 119(6): 493-497, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29960012

RESUMO

Sickle cell disease, the most common genetic disease in the world, is a chronic hemolytic disease that can be complicated by severe vaso-occlusive pain crises resulting in tissue necrosis and even death. Due to its increasing incidence, oral surgeons will inevitably be faced with the management of these patients. To limit the risk of crises, our goal is to share recommendations for the management of sickle cell patients in oral surgery. The vaso-occlusive crises (VOC), heart attacks and chronic anemia endured by these patients cause chronic lesions in various organs. Complications include retinal disease, avascular necrosis, priapism, neurological involvement (cerebrovascular accident), cardiomyopathy, lower limb ulceration, renal and hepatic dysfunction, and cardiopulmonary disease. These complications inevitably lead to an increase in mortality rate. Thorough knowledge of this pathology is essential for the management of these patients in oral surgery. Management strategies include prevention and diagnosis of oral lesions related to sickle cell disease and its treatment, as well as methods of preparation and execution of oral surgery procedures. We suggest guidelines for the management of these complications and implementation of preoperative, intraoperative and postoperative surgical protocols for both practitioners and patients.


Assuntos
Anemia Falciforme , Procedimentos Cirúrgicos Bucais , Priapismo , Cirurgia Bucal , Humanos , Masculino , Dor
6.
J Stomatol Oral Maxillofac Surg ; 119(1): 19-24, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29133198

RESUMO

INTRODUCTION: The main challenge during the osteosynthesis of a bilateral sagittal split osteotomy (BSSO) is to take into account the correct position of the condyle. Adjustable plates can be used to fine-tune the final occlusion without changing the osteosynthesis. A new type of adjustable plate is presented in this article. The aim is to assess the mechanical reliability of this system during the surgery and during the healing period, thanks to a preliminary prospective on 15 consecutive cases. MATERIAL AND METHODS: The bridge of the plate studied here has an "S"-shape and can be bent in two different planes. Fifteen patients presenting a maxilla-mandibular disharmony have been operated on with this device. Clinical results were evaluated three months postoperatively and the mechanical reliability of the device was studied prospectively from teleradiographies of 15 patients operated on in our department. RESULTS: This study shows good results, with respect to the mechanical reliability of this S-shaped adjustable plate, three months postoperatively corresponding to the bone-healing period. Radiographic observations did not show any significant displacement at the osteosynthesis site. DISCUSSION: This preliminary study shows the mechanical reliability of this new S-shaped adjustable plate. Its semi-rigid character may allow for certain condyle position adaptability. No plate fracture was reported for this 15 patient series. These encouraging results have to be confirmed on a larger series.


Assuntos
Placas Ósseas , Osteotomia , Fixação Interna de Fraturas , Humanos , Mandíbula , Reprodutibilidade dos Testes
7.
Rev Stomatol Chir Maxillofac ; 112(6): 353-9, 2011 Dec.
Artigo em Francês | MEDLINE | ID: mdl-22093766

RESUMO

Focal infection of oral origin means that an oral infectious focus may have widespread effects. This concept remains controversial since it is difficult to prove the oral origin of germs responsible for an extra-oral infection. Experiments on animal models and clinical studies suggested several physiopathological mechanisms: bacteremia, toxinic and immunological mechanisms. Various operations induce the passage of bacterial flora (transcytosis) and its toxins into the bloodstream: oral care, chewing, or tooth brushing. Bacteremia is worsened by poor oral hygiene or an infection. The germs are usually destroyed by the host's reticuloendothelial system in a few minutes, but the presence of a valvular disease or a weak immune system favors focal infection. Besides infectious endocarditis, this may concern cardiovascular diseases, lung infections, prematurity and hypotrophy, diabetes, prosthetic infections, cerebral abscesses, etc. This update is based on literature review, selected according to its high level of scientific proof, as well as on a selected choice of consensus conferences. The current recommendation is to limit antibiotic prophylaxis to the high bacteremia risk procedures and to patients highly at risk of developing a focal infection.


Assuntos
Infecção Focal/complicações , Doenças da Boca/complicações , Doenças Estomatognáticas/complicações , Animais , Antibioticoprofilaxia/métodos , Bacteriemia/prevenção & controle , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Endocardite Bacteriana/prevenção & controle , Infecção Focal/diagnóstico , Infecção Focal/epidemiologia , Infecção Focal/terapia , Humanos , Doenças da Boca/diagnóstico , Doenças da Boca/epidemiologia , Doenças da Boca/terapia , Higiene Bucal/efeitos adversos , Infecções Relacionadas à Prótese/complicações , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/terapia , Doenças Estomatognáticas/diagnóstico , Doenças Estomatognáticas/epidemiologia , Doenças Estomatognáticas/terapia
8.
Biol Reprod ; 63(6): 1801-10, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11090452

RESUMO

The nucleus of mammalian spermatozoa is surrounded by a rigid layer, the perinuclear theca, which is divided into a subacrosomal layer and a postacrosomal calyx. Among the proteins characterized in the perinuclear theca, calicin is one of the main components of the calyx. Its sequence contains three kelch repeats and a BTB/POZ domain. We have studied the association of boar calicin with F-actin and the distribution of boar and human calicin during spermiogenesis compared with the distribution of actin. Calicin was purified from boar sperm heads under nondenaturating conditions. The molecule bound actin with high affinity (K(d) = approximately 5 nM), and a stoichiometry of approximately one calicin per 12 actin monomers was observed. Gel filtration studies showed that calicin forms homomultimers (tetramers and higher polymers). According to immunocytochemical results, calicin is present (together with actin) in the acrosomal region of round spermatids and is mainly localized in the postacrosomal region of late spermatids and spermatozoa. Taken together, the results suggest that the affinity of calicin to F-actin allows targeting of calicin at the subacrosomal space of round spermatids, and that its ability to form homomultimers contributes to the formation of a rigid calyx.


Assuntos
Actinas/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteínas dos Microfilamentos/metabolismo , Espermatogênese/fisiologia , Espermatozoides/metabolismo , Sequência de Aminoácidos , Animais , Western Blotting , Separação Celular , Cromatografia em Gel , Cromatografia Líquida de Alta Pressão , Proteínas do Citoesqueleto/isolamento & purificação , Eletroforese em Gel de Poliacrilamida , Humanos , Técnicas In Vitro , Masculino , Microscopia de Fluorescência , Dados de Sequência Molecular , Cabeça do Espermatozoide/química , Cabeça do Espermatozoide/fisiologia , Espermatozoides/química , Suínos , Testículo/citologia
9.
Int J Aging Hum Dev ; 50(1): 73-84, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10735183

RESUMO

The "appropriate" age for retirement as it is perceived by young adults, middle-aged adults, and elderly people has been studied. No respondents were surprised or had trouble expressing an opinion about the minimum and maximum "appropriate" ages for retirement. Representations of the "appropriate" retirement age vary primarily as a function of the perceived physical constraints involved in the occupation, and also depend on the age of the person being questioned; the younger the respondent, and lower the perceived "appropriate" minimum age. There was no tendency among the young adults to prolong the work life of older individuals. Nor was there a tendency to associate aging with the loss of intellectual capacities likely to lead to early retirement.


Assuntos
Atitude , Aposentadoria/psicologia , Estereotipagem , Adulto , Fatores Etários , Idoso , Análise Fatorial , França , Humanos , Pessoa de Meia-Idade , Modelos Psicológicos , Ocupações
10.
J Nucl Med ; 40(1): 192-7, 1999 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9935076

RESUMO

UNLABELLED: In this study a new 99mTc labeling method for polyethyleneglycol (PEG)-coated liposomes is described. The in vitro and in vivo characteristics were compared with the conventional 99mTc-HMPAO-labeled PEG-coated liposomes. METHODS: PEG-coated liposomes were labeled with 99mTc by the hydrazino nicotinyl (HYNIC) derivative of distearoylphosphatidyl-ethanolamine (DSPE) and compared with PEG-coated liposomes labeled with 99mTc-HMPAO. In vitro stability tests were performed. Biodistribution and imaging characteristics of both liposomal preparations were determined in rats with Staphylococcus aureus infection in the left calf muscle. RESULTS: Per liposome, 230 hydrazine groups were incorporated. The labeling efficiency of the 99mTc-HYNIC liposomes was greater than 95%, so no postlabeling purification was required, in contrast to the 99mTc-HMPAO liposomes. The 99mTc-HYNIC liposomes showed greater in vitro stability than the conventional 99mTc-HMPAO liposomes. Abscess uptake of the 99mTc-HYNIC liposomes was significantly greater (1.74+/-0.38%ID/g versus 1.26+/-0.29%ID/g, 24 h postinjection, P < 0.03). Furthermore, kidney uptake of the 99mTc-HYNIC liposomes was one third of the uptake of the 99mTc-HMPAO liposomes (0.79+/-0.07%ID/g versus 2.47+/-0.35%ID/g, 24 h postinjection, P < 0.0001). CONCLUSION: This new 99mTc-HYNIC-based labeling method for liposomes is rapid, efficient and easy to perform. Most importantly, the 99mTc-labeled liposomes have an improved stability and in vivo characteristics. The new labeling method is a major step forward toward a radiopharmaceutical for infection imaging that can be prepared in a one-step procedure within 15 min at room temperature and thus can be applied in every routine clinical practice.


Assuntos
Abscesso/diagnóstico por imagem , Portadores de Fármacos , Lipossomos , Infecções Estafilocócicas/diagnóstico por imagem , Tecnécio , Animais , Câmaras gama , Membro Posterior , Hidrazinas/farmacocinética , Masculino , Niacinamida/análogos & derivados , Niacinamida/farmacocinética , Fosfatidiletanolaminas , Polietilenoglicóis , Cintilografia , Ratos , Ratos Wistar , Tecnécio/farmacocinética , Tecnécio Tc 99m Exametazima , Distribuição Tecidual
11.
Pharmacotherapy ; 18(5): 1001-10, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9758311

RESUMO

The frequency of infertility in developed countries is approximately 8-10%. New drugs are available for assisted reproduction techniques. Two recombinant follicle-stimulating hormone (FSH) products, follitropin-beta (Follistim in the United States, Puregon in Europe) and follitropin-alpha (Gonal-F), join compounds derived through transfecting nonhuman cell lines with genetic material capable of replicating identical amino acid sequences to human compounds. The cell line used for recombinant (r)-FSH production is the Chinese hamster ovary (CHO). Previously, the only agents that showed benefit in controlled ovulatory stimulation were derived from the urine of menopausal women. Those compounds contain additional substances, such as urinary proteins and various amounts of luteininzing hormone. The amino acid sequence of r-FSH is identical to that of human FSH, but the two recombinant products exist in many different isoforms and differ from each other and from human FSH due to varied carbohydrate side chains. Due to variation in the carbohydrate side chains, follitropin-beta in solution has a higher pH than urine-derived FSH, which enhances receptor affinity and therefore is a greater inducer of folliculogenesis. Follitropin-beta does not cause endogenous production of anti-CHO or anti-FSH antibodies, and is well tolerated.


Assuntos
Hormônio Foliculoestimulante/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Ensaios Clínicos como Assunto , Feminino , Hormônio Foliculoestimulante/economia , Humanos , Infertilidade Feminina/economia , Proteínas Recombinantes/uso terapêutico
12.
Hum Genet ; 102(1): 98-102, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9490306

RESUMO

An apparently balanced reciprocal translocation 46,X,t(Y;6) (q11.23 approximately q12;p11.1) was observed in an infertile man with severe oligozooteratozoospermia. Different mitotic chromosome banding patterns were performed and fluorescence in situ hybridization indicated a breakpoint in the fluorescent Yq heterochromatin. Molecular genetic deletion experiments for the azoospermia factor region in distal Yq11 showed the retention of the DAZ gene and meiotic pairing configurations suggested that the man's infertility could be due to the pairing behaviour of the Y;6 translocation chromosome with the X chromosome visualised by synaptonemal complex analysis at the electron microscopy level. The morphological appearance of the normal chromosome 6 and the Y;6 translocated chromosome included in the compartment of the sex vesicle may allow an explanation of the degeneration of most spermatocytes after the pachytene stage.


Assuntos
Infertilidade Masculina/genética , Meiose/genética , Translocação Genética , Cromossomo Y/genética , Adulto , Deleção Cromossômica , Humanos , Masculino , Espermatócitos/patologia , Cromossomo Y/ultraestrutura
13.
Thromb Haemost ; 79(1): 144-9, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9459340

RESUMO

In this study, the clot accumulation properties of liposome-coupled plasminogen were compared to those of free (non-liposomal) plasminogen in an in vitro, closed-loop, flow-system. After introduction of a clot into the closed system, double-radiolabelled plasminogen-liposomes were administered and the accumulation of radiolabel on the entire clot was measured. Liposomal plasminogen showed improved accumulation over free plasminogen, on both a fibrin clot and a whole blood clot. Moreover, once liposomal plasminogen was fibrin associated, it could not be washed away with buffer, in contrast to free plasminogen. Liposomal plasminogen was able to compete successfully with an excess of free plasminogen. The plateau levels for the accumulated amount of plasminogen depended on the incubated amount of plasminogen and were influenced by partial degradation of the clot. Furthermore, it was shown that a threshold liposomal plasminogen surface-density was needed for optimum clot accumulation.


Assuntos
Plasminogênio/administração & dosagem , Trombose/fisiopatologia , Soluções Tampão , Portadores de Fármacos , Fibrina/fisiologia , Modelos Lineares , Lipossomos , Propriedades de Superfície
14.
Mol Reprod Dev ; 48(1): 63-70, 1997 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9266762

RESUMO

Gelsolin, an actin-binding and severing protein present in many mammalian cells, was characterized in human testis. Although abundant in testicular extracts, gelsolin was not detected in purified spermatogenic cells by immunoblot analysis. Immunofluorescence studies of testis sections showed that gelsolin has two main localizations: peritubular cells and the seminiferous epithelium. In peritubular cells, gelsolin was present together with alpha-SM actin, in agreement with the myoid cell characteristics of these cells. In a large proportion of the tubules, gelsolin was found mainly, together with actin, in the apical part of the seminiferous epithelium. This localization of gelsolin also was observed in seminiferous tubules with a partial or complete absence of germinal cells, which evokes a presence of gelsolin at the apex of Sertoli cells. However, in normal testis, a complex pattern of gelsolin labeling was also present, mostly in the apical third of the epithelium, around cells or groups of cells, mainly spermatids, and, less frequently, in various other localizations from the apical to the basal part of the seminiferous epithelium. Taken together, these observations suggest that gelsolin may play different functions in the seminiferous epithelium: (1) regulation of the dynamic alterations of the actin cytoskeleton in the apical cytoplasm of Sertoli cells, and (2) modification of actin filaments assemblies in specific structures at germ cell-Sertoli cell contacts. Thereby, the actin-modulating properties of gelsolin are probably involved in reorganization of the seminiferous epithelium related to germ cell differentiation.


Assuntos
Gelsolina/metabolismo , Testículo/metabolismo , Animais , Humanos , Masculino , Camundongos , Testículo/citologia
15.
Hum Genet ; 98(4): 505-7, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8792831

RESUMO

The proximal long arm of the Y chromosome probably contains a gene (GCY) involved in stature determination. Recent reports have proposed the critical region extends from interval 4B to interval 5G (or 5E). In the present study, the deletion breakpoint in a male adult patient of normal height with a 46,X,del(Yq) karyotype was defined by the use of sequence-tagged site markers. The breakpoint was found between sY78 (interval 4B) and sY79 (interval 5A). The existence of a normal stature in this patient suggests that the growth determinant is proximal to sY79, therefore probably located in interval 4B or in proximal interval 5A of the Y chromosome.


Assuntos
Deleção Cromossômica , Cromossomo Y , Adulto , Estatura , Mapeamento Cromossômico , Proteína 1 Suprimida em Azoospermia , Humanos , Cariotipagem , Linfócitos , Masculino , Oligospermia/genética , Reação em Cadeia da Polimerase , Proteínas de Ligação a RNA/genética , Sêmen , Sitios de Sequências Rotuladas , Cromossomo X
16.
Thromb Haemost ; 75(1): 134-9, 1996 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-8713792

RESUMO

In this study, the fibrin binding properties of liposomes containing a number of plasminogen (Plg) molecules on the outside were compared to those of free (non-liposomal) Plg in an in vitro model system. Fibrin monolayer coated 96-wells plates were used, containing fibrin monomer at a density of around 3.4 to 3.9 x 10(-4) nmol/cm2. These densities are similar to liposomal Plg-densities, thus allowing multivalent interactions to occur. In the panel of experimental conditions that was chosen, binding of free Plg and liposomes with Plg showed three main differences in characteristics. Firstly, in the fibrin binding of Plg-liposomes not all Plg may be involved, but on the average 40% of the total amount of liposomal Plg. This was shown by lysing the liposomes after binding to the fibrin and estimation of truly bound Plg. With Plg-densities on the liposomes below the fibrin binding sites density, the maximal number of bound Plg molecules remains below the amount of available fibrin binding sites. Secondly, a higher binding rate by at least one order of magnitude was observed for liposomes with Plg compared to free Plg. Thirdly, liposomes with Plg exhibit a fibrin binding affinity which increases with Plg-density, because of the multivalent character of interaction. Liposomal Plg can successfully compete for fibrin binding sites with a 100 fold higher concentration of free Plg. These in vitro findings indicate that in view of avid and rapid fibrin binding, liposomes with attached plasminogen may be suitable for in vivo targeting to fibrin based thrombi.


Assuntos
Fibrina/metabolismo , Lipossomos/química , Plasminogênio/metabolismo , Sequência de Aminoácidos , Ligação Competitiva , Humanos , Técnicas In Vitro , Radioisótopos do Iodo , Dados de Sequência Molecular , Ligação Proteica , Propriedades de Superfície
18.
Biol Reprod ; 52(5): 1066-72, 1995 May.
Artigo em Inglês | MEDLINE | ID: mdl-7626706

RESUMO

The presence in human sperm nuclear proteins of a limited amount of unoxidized thiol groups, stabilized by reversible binding to zinc ions, has been presumed to play a role in the decondensation of sperm within the oocyte. In the present study, the number and molecular localization of free sulfhydryls in the major proteins of human sperm chromatin, protamines P1 and P2, were determined by alkylation of reactive thiols with 14C-iodoacetamide, isolation of protamines, and peptide mapping. Less than 1.5% of the cysteines of protamines were found as reactive thiols, a proportion strikingly lower than that reported previously for whole human sperm proteins. The amount of sulfhydryls was unaffected by the zinc chelating agent EDTA. Labeling was evenly distributed on every cysteine of protamines P1 and P2. The results confirm the extensive stabilization of sperm chromatin by disulfide bridges and show that the unoxidized cysteines remaining at the end of epididymal transit in some protamine molecules may be one of the six (protamine P1) or five (protamine P2) cysteines present in the sequence of each class of protamines. This even distribution of the reactive cysteines could facilitate decondensation of sperm nuclei initiated by a thiol-disulfide exchange.


Assuntos
Cromatina/química , Proteínas Nucleares/análise , Espermatozoides/química , Compostos de Sulfidrila/análise , Alquilação , Sequência de Aminoácidos , Cisteína/análise , Ácido Edético/farmacologia , Humanos , Masculino , Dados de Sequência Molecular , Mapeamento de Peptídeos , Protaminas/análise , Protaminas/química
19.
Thromb Haemost ; 73(3): 488-94, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7667833

RESUMO

In this study, we aimed at improving the therapeutic index of tissue-type Plasminogen Activator (t-PA) as thrombolytic agent in the treatment of myocardial infarction. Liposome-encapsulated t-PA was tested in a rabbit jugular vein thrombosis model: administration of free t-PA (t-PA) as a bolus injection in the ear vein was compared to a similar administration of liposomal t-PA (t-PA-lip), liposomal t-PA in plasminogen-coated liposomes (Plg-t-PA-lip), a mixture of free t-PA and empty liposomes (t-PA+ empty lip) and a saline-blank (blank) in terms of thrombolytic activity and side effects. Liposomal t-PA (t-PA-lip/Plg-t-PA-lip) showed a significantly better thrombolysis efficiency than equimolar doses of free t-PA (t-PA/ t-PA+ empty lip): about 0.24 mg/kg of liposomal t-PA practically equalled the lysis-activity of a dose of free t-PA of 1.0 mg/kg (t-PA1mg/kg). On the other hand, liposome encapsulation did not affect the systemic activation of alpha 2-antiplasmin and plasminogen by t-PA. We conclude that for this model an improvement in thrombolytic efficacy of t-PA is achieved by liposome encapsulation of t-PA. As t-PA-lip and Plg-t-PA-lip -treatment induced similar results, targeting of liposomal t-PA by coupled glu-Plg remains a topic to be optimized in future studies.


Assuntos
Lipossomos , Terapia Trombolítica , Trombose/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Animais , Portadores de Fármacos , Composição de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Veias Jugulares , Plasminogênio/administração & dosagem , Plasminogênio/análise , Coelhos , Ativador de Plasminogênio Tecidual/farmacocinética , Ativador de Plasminogênio Tecidual/uso terapêutico , Ativador de Plasminogênio Tecidual/toxicidade
20.
J Drug Target ; 3(4): 301-10, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8821004

RESUMO

UNLABELLED: In this study, a method was developed for the efficient entrapment of active tissue-type Plasminogen Activator (t-PA) into liposomes. Experimental conditions were varied to optimize t-PA entrapment: different buffer solutions were used (pH 4 and 7.5), the effect of the incubation concentrations of phospholipid (PL) and t-PA was monitored and the influence of liposome-size was examined. Furthermore, the effect of ultracentrifugation on t-PA containing liposomes was determined in the presence and absence of Tween 80. t-PA entrapment strongly depended on experimental conditions and ranged from 30 up to 90%. Almost quantitative+ (90%) entrapment (entrapment percentage defined as absolute entrapment (IU t-PA/mumol PL) divided by total incubation ratio (IU t-PA/mumol PL), times 100%) was obtained in Hepes buffer pH 7.5, devoid of arginine, with low ionic strength. Ultracentrifugation, used for removal of non-entrapped t-PA, was shown to have a damaging effect on the liposomes (especially in the presence of 0.05% Tween 80), leading to t-PA loss. However, because acceptable alternatives were not available, ultracentrifugation was used during this study. Therefore, the encapsulation-percentage values shown in this study are in fact underestimates for the true entrapment of t-PA. IN CONCLUSION: almost quantitative t-PA entrapment in liposomes can be achieved by selecting the proper milieu and inducing a strong interaction between t-PA and bilayer.


Assuntos
Ativador de Plasminogênio Tecidual/administração & dosagem , Soluções Tampão , Composição de Medicamentos , Estabilidade de Medicamentos , Congelamento , Humanos , Lipossomos , Tamanho da Partícula , Fosfolipídeos/química , Polissorbatos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/química , Ativador de Plasminogênio Tecidual/química , Ultracentrifugação
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