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1.
Inj Epidemiol ; 5(1): 27, 2018 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-29961925

RESUMO

BACKGROUND: Private and Public security and law enforcement (SLE) sectors perform multiple overlapping job duties. METHODS: Workers' compensation (WC) SLE first reports of injury (FROI) data (2005-2015) were analyzed to describe injuries, identify differences in awarded WC benefits, and compare the probability of a FROI resulting in awarded benefits between Public and Private SLE. A Pearson's chi-square test was utilized and reverse selection logistic regression was performed to estimate the odds ratio that a FROI would result in an awarded benefit for Private vs. Public SLE, while adjusting for relevant covariates. RESULTS: Private SLE had higher FROI percentages for younger and for older workers, fall injuries, and back injuries, compared to Public SLE. The adjusted odds that a FROI resulted in an awarded benefit was 1.4 times higher for Private SLE compared to Public SLE; (95% confidence interval [CI] = 1.09,1.69). Middle-aged SLE employee adjusted odds of awarded benefits was 3.3 times (95% CI [1.96, 5.39]) higher compared to younger employees. Adjusted odds of awarded benefits was 3.8 times (95% CI [1.34, 10.61]) higher for gunshots and 1.7 times (95% CI [1.22, 2.39]) higher for fractures/dislocations compared to other nature of injuries. Motor vehicle injury, fall/slip, and strain related FROIs had elevated adjusted odds of awarded benefits compared to other injury causes. CONCLUSIONS: Results highlight the importance of injury prevention education and worker safety training for Private and Public SLE sector workers on fall prevention (especially in Private SLE) and strain prevention (especially in Public SLE), as well as motor vehicle safety.

2.
Clin Infect Dis ; 37(12): 1585-90, 2003 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-14689335

RESUMO

Fresh produce increasingly is recognized as an important source of salmonellosis in the United States. In December 1999, the Centers for Disease Control and Prevention detected a nationwide increase in Salmonella serotype Newport (SN) infections that had occurred during the previous month. SN isolates recovered from patients in this cluster had indistinguishable pulsed-field gel electrophoresis (PFGE) patterns (which identified the outbreak strain), suggesting a common source. Seventy-eight patients from 13 states were infected with the outbreak strain. Fifteen patients were hospitalized; 2 died. Among 28 patients enrolled in the matched case-control study, 14 (50%) reported they ate mangoes in the 5 days before illness onset, compared with 4 (10%) of the control subjects during the same period (matched odds ratio, 21.6; 95% confidence interval, 3.53- infinity; P=.0001). Traceback of the implicated mangoes led to a single Brazilian farm, where we identified hot water treatment as a possible point of contamination; this is a relatively new process to prevent importation of an agricultural pest, the Mediterranean fruit fly. This is the first reported outbreak of salmonellosis implicating mangoes. PFGE was critical to the timely recognition of this nationwide outbreak. This outbreak highlights the potential global health impact of foodborne diseases and newly implemented food processes.


Assuntos
Surtos de Doenças , Mangifera/microbiologia , Infecções por Salmonella/epidemiologia , Salmonella enterica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Infecções por Salmonella/microbiologia , Estados Unidos/epidemiologia
3.
Int J Pharm ; 249(1-2): 233-45, 2002 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-12433451

RESUMO

An inhaler adapter has been designed for the characterization of the aerosol clouds from medical aerosol generators such as nebulizers, dry powder inhalers (dpis) and metered dose inhalers (mdis) with laser diffraction technology. The adapter has a pre-separator, for separation of large particles (i.e. carrier crystals) from the aerosol cloud before it is exposed to the laser beam. It also has a fine particle collector for measuring the emitted mass fraction of fines by chemical detection methods after laser diffraction sizing. The closed system enables flow control through the aerosol generators and all test conditions, including ambient temperature and relative humidity, are automatically recorded. Counter flows minimize particle deposition onto the two windows for the laser beam, which make successive measurements without cleaning of these windows possible. The adapter has successfully been tested for nebulizers, mdis and dpis. In a comparative study with ten nebulizers it was found that these devices differ considerably in droplet size (distribution) of the aerosol cloud for the same 10% aqueous tobramycin solution (volume median diameters ranging from 1.25 to 3.25 microm) when they are used under the conditions recommended by the manufacturers. The droplet size distribution generated by the Sidestream (with PortaNeb compressor) is very constant during nebulization until dry running of the device. Comparative testing of dpis containing spherical pellet type of formulations for the drug (e.g. the AstraZeneca Turbuhaler) with the adapter is fast and simple. But also formulations containing larger carrier material could successfully be measured. Disintegration efficiency of a test inhaler with carrier retainment (acting as a pre-separator) could be measured quite accurately both for a colistin sulfate formulation with 16.7% of a lactose fraction 106-150 microm and for a budesonide formulation with a carrier mixture of Pharmatose 325 and 150 M. Therefore, it is concluded that, with this special adapter, laser diffraction may be a valuable tool for comparative inhaler evaluation, device development, powder formulation and quality control. Compared to cascade impactor analysis, laser diffraction is much faster. In addition to that, more detailed and also different information about the aerosol cloud is obtained.


Assuntos
Aerossóis/química , Lasers , Nebulizadores e Vaporizadores , Administração por Inalação , Nebulizadores e Vaporizadores/normas , Tamanho da Partícula
4.
J Epidemiol Community Health ; 56(5): 354-61, 2002 May.
Artigo em Inglês | MEDLINE | ID: mdl-11964432

RESUMO

STUDY OBJECTIVE: To review existing data on social class gradients in adolescent health and to examine whether such gradients exist in new data concerning US adolescents. DESIGN: Review of relevant publications and unpublished data; regression analyses using adolescent self reported health status data to determine whether there are gradients by social class, using three classes categorised by adolescent reported parental work status and education. PARTICIPANTS: Adolescents of ages 11-17. MAIN RESULTS: Findings from the literature indicate the presence of social class gradients in some but not all aspects of adolescent health. Results from new data showed social class gradients in several domains of health and in profiles of health. The likelihood of being satisfied with one's health, of being more resilient (better family involvement, better problem solving, more physical activity, better home safety), having higher school achievement, and of being in the best health profiles were significantly and progressively greater as social class rose. Moreover, the probability of being in the poorest health profile type group was progressively higher as social class declined. CONCLUSIONS: The review of existing data and the new findings support the existence of social class gradients in satisfaction with one's health, in resilience to health threats, in school achievement, and in being in the best health overall (as manifested by the health profiles composed of four major domains of health). The study had two especially notable findings: (1) the paucity of studies using the same or similar indicators, and (2) the consistent existence of social class gradients in characteristics related to subsequent health, particularly intake of nutritional foods and physical activity. The sparseness of existing data and the different aspects of health investigated in the relatively few studies underscore the need for (1) the development of conceptual models specifically focused on adolescent health and social class; (2) additional inquiry into the measurement of social class and adolescent perceptions of class; (3) inclusion of contextual variables in study design; and (4) longitudinal cohort studies to better understand the specific determinants of health during adolescence.


Assuntos
Nível de Saúde , Classe Social , Adolescente , Comportamento do Adolescente , Adulto , Fatores Etários , Estatura , Criança , Inquéritos Epidemiológicos , Humanos , Morbidade , Mortalidade , Análise de Regressão , Saúde da População Rural , Fatores Sexuais , Estados Unidos/epidemiologia , Ferimentos e Lesões/epidemiologia
5.
Free Radic Biol Med ; 30(10): 1145-53, 2001 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-11369505

RESUMO

Vitamin E supplementation exhibits anti-inflammatory properties. In the lung, the beneficial effects of vitamin E supplementation on inflammation and infections are well documented, but potential consequences of alimentary vitamin E deficiency to the immunological status of lung cells are not known. It is unclear if temporary vitamin E deficiency exhibits deleterious consequences or can be compensated for by other cellular antioxidants. To address this question, the alimentary vitamin E supply to rats was modified. We then investigated the effects on major histocompatibility molecule (MHC) class II, cell adhesion molecules, interleukin (IL)10, tumor necrosis factor (TNF)alpha in various lung cells. The constitutive expression of MHC class II, intercellular adhesion molecule (ICAM)-1, L-selectin, alpha5-integrin, and CD 166, was demonstrated by flow cytometry on type II pneumocytes, alveolar macrophages, and on co-isolated lymphocytes. Vitamin E depletion increased ICAM-1 and CD166 on type II cells and macrophages, whereas the expression of L-selectin increased only on macrophages. Furthermore, the vitamin E depletion increased the cellular content and secretion of IL10 in type II cells, but decreased the content and secretion of TNFalpha. Vitamin E depletion decreased the cellular vitamin E content, but did not change the activity of antioxidant enzymes (catalase, superoxide dismutase) and the glutathion (GSH)/oxidized glutathion (GSSG) ratio in alveolar type II cells. The shift of protein kinase C (PKC) from the cytosol to membranes indicates that a PKC-dependent signaling pathway may be involved in the change of the immunological status of type II cells. All these effects were reversed by vitamin E repletion. In summary, these results are clearly compatible with the view that a temporary vitamin E deficiency induces a reversible immunological dysregulation in alveolar type II cells and lung macrophages. This deficiency might predispose the lung to develop acute or chronic inflammation.


Assuntos
Pulmão/imunologia , Pulmão/patologia , Deficiência de Vitamina E/imunologia , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Moléculas de Adesão Celular/metabolismo , Sobrevivência Celular , Ativação Enzimática/efeitos dos fármacos , Citometria de Fluxo , Glutationa/metabolismo , Antígenos de Histocompatibilidade Classe II/imunologia , Antígenos de Histocompatibilidade Classe II/metabolismo , Imunoquímica , Interleucina-10/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/patologia , Proteína Quinase C/metabolismo , Ratos , Ratos Wistar , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Vitamina E/metabolismo , Vitamina E/farmacologia , Deficiência de Vitamina E/dietoterapia , Deficiência de Vitamina E/patologia
6.
Appl Opt ; 40(16): 2595-600, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-18357273

RESUMO

Measurements of the angular spectrum of light transmitted through turbid slabs with monodispersions of polystyrene spheres have been performed. The results obtained are compared with theoretical calculations, based on the small-angle approximation of the radiative transfer theory. The experimental data and the theoretical results coincide with a high accuracy, which allows us to develop the laser diffraction spectroscopy of optically thick light-scattering layers.

7.
J Lipid Res ; 41(12): 2009-16, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11108734

RESUMO

The scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesterol and cholesteryl ester (CE) from high density lipoprotein (HDL) into cells. The high expression in liver and steroidogenic tissues is compatible with a role of SR-BI in reverse cholesterol transport and steroid hormone synthesis. Ways of regulation thus far described include induction by trophic hormones via cAMP-activated protein kinase A (PKA) and the effects of cellular and plasma cholesterol. Here we show that vitamin E (vitE) has a major effect on the expression of SR-BI in rat liver and in a human hepatoma-derived cell line, HepG2. Feeding rats a vitE-depleted diet resulted in an 11-fold increase in the SR-BI protein level in liver tissue. This effect was readily reversed by feeding a vitE-enriched chow. In HepG2 cells, the expression of the human SR-BI homolog was reduced when the vitE content was increased by incubating the cells with vitE-loaded HDL or with phosphatidylcholine/vitE vesicles. The downregulation of human SR-BI (hSR-BI) was accompanied by a reduced level of protein kinase C (PKC) in the particulate cell fraction, and PKC inhibition decreased the expression of hSR-BI and the uptake of vitE and cholesterol from HDL. Our results are consistent with the view that the cellular level of vitE exerts a tight control over the expression of SR-BI. Furthermore, the inhibitory effect of vitE on PKC seems to be involved in the signaling pathway.


Assuntos
Antígenos CD36/metabolismo , Fígado/efeitos dos fármacos , Proteínas de Membrana , Receptores Imunológicos , Receptores de Lipoproteínas , Vitamina E/farmacologia , Animais , Regulação para Baixo , Humanos , Lipoproteínas HDL/metabolismo , Fígado/metabolismo , Masculino , Proteína Quinase C/metabolismo , Ratos , Ratos Wistar , Receptores Depuradores , Receptores Depuradores Classe B , Transdução de Sinais , Células Tumorais Cultivadas , Deficiência de Vitamina E/metabolismo
8.
Lung ; 178(4): 191-200, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-10960554

RESUMO

Vitamin E is the most important lipophilic antioxidant, and beneficial effects on oxidant-caused injuries have been reported. Neonates are at high risk of oxidative injury in the lung and other organs because of a low vitamin E concentration, but the optimal timing of the application, a safe application form, and the optimal dosage of vitamin E are not known at present. We recently showed that alveolar type II cells take up vitamin E preferentially from high-density lipoprotein (HDL), probably by means of the candidate HDL receptor, scavenger receptor class B type I (SR-BI; Kolleck et al. Free Rad Biol Med 27; 882-890, 1999). Therefore, both the HDL-bound vitamin E in plasma and the expression of SR-BI on alveolar type II cells may determine the supply of the cells with vitamin E. We show here that the plasma level of vitamin E, total and HDL cholesterol, and the ratio of vitamin E to polyunsaturated fatty acids and to total fatty acids decrease during fetal rat development, reaching the minimum at the postconceptual day 21 (day -1). These parameters increase thereafter to about the same levels as in adult rats. SR-BI is not detectable until day -1 on fetal lung cells, but the expression during the postnatal phase follows the same pattern as the plasma lipid constituents. We conclude that the ability of alveolar type II cells to take up vitamin E develops perinatally in mature neonates. This aspect also has to be considered when the optimal timing of supplementation for the protection of preterm neonates with vitamin E against oxidative lung injury is established.


Assuntos
Antígenos CD36/metabolismo , Lipoproteínas HDL/sangue , Pulmão/metabolismo , Proteínas de Membrana , Receptores Imunológicos , Receptores de Lipoproteínas/metabolismo , Vitamina E/sangue , Animais , Animais Recém-Nascidos , Feto , Imuno-Histoquímica , Fígado/metabolismo , Macrófagos Alveolares/metabolismo , Ratos , Receptores Depuradores , Receptores Depuradores Classe B , Fatores de Tempo
9.
Am J Respir Cell Mol Biol ; 22(6): 739-46, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10837372

RESUMO

Numerous communications have indicated that specific binding proteins for high density lipoprotein (HDL) exist in addition to the well characterized candidate HDL receptor SR-BI, but structural information was presented only in a few cases, and most of the work was aimed at the liver and steroidogenic glands. In this study, we purified two HDL-binding proteins by standard procedures from rat lung tissue. One of these membrane glycoproteins was identified by N-terminal sequencing and with specific antibodies as HB2, a previously described HDL-binding protein, whereas the other one was identified as a glycosyl phosphatidylinositol-anchored membrane dipeptidase (MDP). The apparent dissociation constant of the HDL binding was determined by solid phase assay to be 2.1 microg/ml (HB2) and 25 microg/ml (MDP). MDP also exerts affinity to low density lipoprotein (LDL) on ligand blots, and competition between HDL and LDL was observed, but analysis by solid phase assay showed that very high concentrations of LDL are required. The physiologic relevance of this effect is therefore questionable. The level in type II pneumocyte membranes of both binding proteins, MDP and HB2, increased when the plasma lipoprotein concentration was reduced by treatment of rats with 4-aminopyrazolo[3,4-d]-pyrimidine, consistent with a function to facilitate lipid uptake in vivo. The binding proteins were also dramatically upregulated by feeding rats a vitamin E-depleted diet. Vitamin E uptake requires interaction between HDL and type II cells, suggesting a role of HB2 and MDP also in this process.


Assuntos
Proteínas de Ligação a DNA/metabolismo , Dipeptidases/metabolismo , Glicosilfosfatidilinositóis/metabolismo , Pulmão/citologia , Pulmão/enzimologia , Proteínas de Membrana/metabolismo , Sequência de Aminoácidos , Animais , HDL-Colesterol/análise , HDL-Colesterol/metabolismo , Proteínas de Ligação a DNA/análise , Proteínas de Ligação a DNA/química , Dieta , Eletroforese , Lectinas , Masculino , Proteínas de Membrana/análise , Proteínas de Membrana/química , Dados de Sequência Molecular , Ratos , Ratos Wistar , Deficiência de Vitamina E/metabolismo
10.
J Gerontol A Biol Sci Med Sci ; 54(11): B492-501, 1999 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-10619312

RESUMO

The collaborative Interagency Agreement between the National Center for Toxicological Research (NCTR) and the National Institute on Aging (NIA) was aimed at identifying and validating a panel of biomarkers of aging in rodents in order to rapidly test the efficacy and safety of interventions designed to slow aging. Another aim was to provide a basis for developing biomarkers of aging in humans, using the assumption that biomarkers that were useful across different genotypes and species were sensitive to fundamental processes that would extrapolate to humans. Caloric restriction (CR), the only intervention that consistently extends both mean and maximal life span in a variety of species, was used to provide a model with extended life span. C57BI/6NNia, DBA/2JNia, B6D2F1, and B6C3F1 mice and Brown Norway (BN/RijNia), Fischer (F344/NNia) and Fischer x Brown Norway hybrid (F344 x BN F1) rats were bred and maintained on study. NCTR generated data from over 60,000 individually housed animals of the seven different genotypes and both sexes, approximately half ad libitum (AL) fed, the remainder CR. Approximately half the animals were shipped to offsite NIA investigators internationally, with the majority of the remainder maintained at NCTR until they died. The collaboration supplied a choice of healthy, long-lived rodent models to investigators, while allowing for the development of some of the most definitive information on life span, food consumption, and growth characteristics in these genotypes under diverse feeding paradigms.


Assuntos
Crescimento , Longevidade , Envelhecimento , Animais , Biomarcadores , Peso Corporal , Ingestão de Alimentos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Ratos , Ratos Endogâmicos BN , Ratos Endogâmicos F344
11.
J Chromatogr B Biomed Sci Appl ; 705(1): 127-31, 1998 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-9498679

RESUMO

A new method for the quantitation of lipoic acid in plasma and tissues based on the selective precolumn derivatization of thiols with the fluorescent label monobromobimane is described. After extraction with diethyl ether, the dithiolane ring of lipoic acid is opened by reduction with NaBH4 before the free thiols can react with the label. Separation and quantitation was achieved by reversed-phase HPLC and fluorescence detection. The concentration-response curve was linear from 20 to 3000 nM in plasma. The recovery as determined with [3H]lipoic acid was 60.9% from plasma and 61.4% from rat heart tissue. The pretreatment of samples with N-ethylmaleimide makes it possible to differentiate between reduced and oxidized forms of lipoic acid.


Assuntos
Compostos Bicíclicos com Pontes , Compostos Bicíclicos com Pontes/análise , Corantes Fluorescentes , Ácido Tióctico/análise , Animais , Compostos Bicíclicos com Pontes/química , Cromatografia Líquida de Alta Pressão , Humanos , Miocárdio/química , Ratos , Sensibilidade e Especificidade , Espectrometria de Fluorescência , Ácido Tióctico/análogos & derivados , Ácido Tióctico/sangue
14.
JAMA ; 274(19): 1510, 1995 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-7474218
15.
Circulation ; 90(1): 421-6, 1994 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-8026028

RESUMO

BACKGROUND: DSPA (Desmodus salivary plasminogen activator) is a new thrombolytic agent corresponding to a natural plasminogen activator discovered in the saliva of the vampire bat Desmodus rotundus. Compared with tissue plasminogen activator (TPA), DSPA, produced in a recombinant cell line, is more fibrin cofactor dependent than TPA. METHODS AND RESULTS: The thrombolytic properties of DSPA and TPA were compared in a canine model of copper coil-induced coronary thrombosis. All dogs received heparin 200 IU/kg IV and SC. Whereas controls did not reperfuse within 180 minutes (none of six), intravenous bolus administration of DSPA at 25, 50, and 100 micrograms/kg resulted in a 100% incidence (6 of 6) of recanalization within 37, 23, and 18 minutes, respectively. TPA at 63 and 125 micrograms/kg reopened the coronaries in 33% (two of six) and 50% (three of six) of cases within 40 minutes. Eighty-three percent (5 of 6) of the arteries were still patent 3 hours after 50 and 100 micrograms/kg DSPA, whereas only 20% (one of five) of all coronaries originally recanalized with both doses of TPA were still open at 3 hours. Plasma levels of alpha 2-antiplasmin decreased significantly only with 125 micrograms/kg TPA. The clearance of DSPA (2.3 to 3.5 mL.min-1.kg-1) was lower compared with TPA (11.4 to 20 mL.min-1.kg-1) due to a prolonged terminal half-life. CONCLUSIONS: In a canine coronary thrombosis model, DSPA exhibited higher potency and recanalized coronary arteries faster and with a lower incidence of reocclusion than TPA. Its properties may translate into a higher efficacy in patients compared with available thrombolytic agents. The long half-life of DSPA may allow for single bolus administration in the treatment of acute myocardial infarction.


Assuntos
Trombose Coronária/terapia , Ativadores de Plasminogênio/uso terapêutico , Terapia Trombolítica , Animais , Trombose Coronária/sangue , Cães , Hemostasia/efeitos dos fármacos , Infusões Intravenosas , Masculino , Ativadores de Plasminogênio/farmacocinética , Fatores de Tempo , Ativador de Plasminogênio Tecidual/farmacocinética , Ativador de Plasminogênio Tecidual/uso terapêutico
16.
Blood Coagul Fibrinolysis ; 5(2): 243-8, 1994 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-8054457

RESUMO

The aims of the present investigation were to develop a new venous thrombosis animal model with low flow conditions in the venous blood stream and then evaluate this model for testing new anticoagulants. In this model, the vena cava of rats was narrowed with a Doppler flow probe, blood flow velocity continuously recorded and thrombus formation initiated by thromboplastin infusion. Sixty-five minutes following thromboplastin infusion the animals were sacrificed and the following parameters measured: thrombus wet weight, fibrinopeptide A (FpA), activated partial thromboplastin time and platelet number. The new model was evaluated with aspirin, a PGI2 mimetic, heparin and a soluble thrombomodulin analogue. Without thromboplastin infusion no thrombus formation or reduction of blood flow was observed. Controls receiving thromboplastin infusion developed a thrombus, blood flow was arrested, platelet number decreased and FpA was elevated. In contrast, animals pretreated with anticoagulants maintained a residual flow, while thrombus weight, thrombocytopenia and FpA elevation were reduced. The antiplatelet agents were not effective. This study demonstrates that, under low flow conditions, only a combination of blood flow reduction with a hypercoagulable state results in venous thrombus formation. This improved model of venous thrombosis more closely resembles the clinical situation and is applicable for testing anticoagulants.


Assuntos
Tromboflebite/fisiopatologia , Animais , Anticoagulantes/farmacologia , Aspirina/farmacologia , Velocidade do Fluxo Sanguíneo , Constrição , Modelos Animais de Doenças , Epoprostenol/análogos & derivados , Epoprostenol/farmacologia , Heparina/farmacologia , Masculino , Inibidores da Agregação Plaquetária/farmacologia , Prostaglandinas Sintéticas/farmacologia , Ratos , Ratos Wistar , Proteínas Recombinantes/farmacologia , Trombomodulina/fisiologia , Tromboplastina/farmacologia , Veia Cava Inferior
17.
Ann N Y Acad Sci ; 667: 395-403, 1992 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-1309059

RESUMO

The saliva of D. rotundus contains at least four plasminogen activators (PAs) which all require fibrin as a cofactor. D. rotundus salivary PAs (DSPAs) exhibit a sequential array of structural motifs such as "Finger" (F), "EGF" (E), "Kringle" (K) and "Protease" (P) which was elucidated by cDNA cloning and sequencing. The respective domain organizations are: FEKP (DSPA alpha 1 and DSPA alpha 2), EKP (DSPA beta) and KP (DSPA gamma). In all four forms the plasmin-sensitive site of tPA is obliterated, indicating that they function as single-chain enzymes. DSPA alpha 1 differs from alpha 2 by amino acid substitutions found mainly in the F, E and K domain, 11% of the total sequence. DSPA beta and gamma, while being closely related to alpha 2, still exhibit 2 and 13 amino acid exchanges, respectively. These sequence heterogeneities, together with results of Southern blot hybridization experiments, strongly suggest that the four DSPA mRNA species originate from different genes. All four forms of DSPA have been expressed in animal cell culture and DSPA alpha 1 was chosen for a detailed pharmacological characterization. In vitro DSPA alpha 1 activity is enhanced 50,000-fold in the presence of fibrin, whereas the activity of single chain tPA is only enhanced 100-fold. At equally effective thrombolytic doses DSPA causes lower bleeding incidence in a rat mesenteric vein model and exhibits high potency, clot selectivity, and speed in the dissolution of fibrin embolized into the lung of anesthetized rats. In the copper coil-induced dog coronary heart infarction model, at doses that achieve patency at equal rates, reocclusion is significantly less frequent than with tPA. These results indicate that DSPA alpha 1 may be a safer and more efficacious thrombolytic agent than the PAs currently in clinical use.


Assuntos
Quirópteros , Fibrinólise/efeitos dos fármacos , Ativadores de Plasminogênio/farmacologia , Saliva/química , Sequência de Aminoácidos , Animais , Cromatografia de Afinidade , Cromatografia por Troca Iônica , Eletroforese em Gel de Poliacrilamida , Humanos , Cinética , Dados de Sequência Molecular , Ativadores de Plasminogênio/biossíntese , Ativadores de Plasminogênio/isolamento & purificação , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia , Homologia de Sequência de Aminoácidos , Ativador de Plasminogênio Tecidual/química
19.
Cancer Nurs ; 15(5): 331-46, 1992 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1423252

RESUMO

Cancer pain continues to remain a significant problem for oncology patients treated in both the university and the community setting. Nursing knowledge regarding pain management has advanced significantly in recent years. This article provides health care professionals with current factual information on cancer pain management. The information focuses on the emotional aspects of cancer pain, specific principles of analgesic management, opioid equianalgesics, multiple approaches to opioid administration, management of unwanted side effects, and a description of inappropriate drug therapies.


Assuntos
Analgésicos/uso terapêutico , Neoplasias/fisiopatologia , Enfermagem Oncológica/métodos , Dor/tratamento farmacológico , Analgesia Controlada pelo Paciente/enfermagem , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Avaliação em Enfermagem , Registros de Enfermagem , Dor/etiologia , Dor/enfermagem
20.
Blood ; 79(5): 1213-7, 1992 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-1536947

RESUMO

rDSPA alpha 1 (recombinant Desmodus salivary plasminogen activator alpha 1) is a recombinant protein corresponding to a natural plasminogen activator from the vampire bat Desmodus rotundus. The thrombolytic properties of rDSPA alpha 1 and tissue-type plasminogen activator (t-PA) were compared in a rat model of pulmonary embolism. Whole blood clots, produced in vitro and labeled with 125I-fibrinogen, were embolized into the lungs of anesthetized rats. Thrombolysis was calculated from the difference between initial clot radioactivity and that remaining in the lungs at 60 minutes. Blood was sampled for gamma counting, measurement of hemostatic factors, and plasminogen activator antigen levels. Thrombolysis at 3, 10, 30, and 100 nmol/kg intravenously (10% bolus, 90% over 60 minutes) amounted to 30% +/- 2%, 51% +/- 4%, 85% +/- 4%, 98% +/- 0% for rDSPA alpha 1 and 30% +/- 3%, 41% +/- 3%, 57% +/- 6%, 93% +/- 2% for t-PA (controls: 29% +/- 2%; mean +/- SEM, n greater than or equal to 6). t-PA at 100 nmol/kg significantly decreased fibrinogen, plasminogen, and alpha 2-antiplasmin levels by 33% +/- 7%, 38% +/- 8%, and 61% +/- 9%, whereas rDSPA alpha 1 at 100 nmol/kg only lowered alpha 2-antiplasmin significantly (by 29% +/- 6%). Compared with t-PA, rDSPA alpha 1 is the more potent and more clot selective (fibrin specific) thrombolytic agent. These results suggest that rDSPA alpha 1 may be safer and more efficacious than currently used thrombolytics.


Assuntos
Quirópteros , Ativadores de Plasminogênio/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Saliva/química , Terapia Trombolítica , Animais , Fibrinogênio/metabolismo , Masculino , Plasminogênio/metabolismo , Ratos , Ratos Endogâmicos , Proteínas Recombinantes/uso terapêutico , Ativador de Plasminogênio Tecidual/uso terapêutico , alfa 2-Antiplasmina/metabolismo
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