RESUMEN
Studies with mammals and birds clearly demonstrate that brief preexposure to oxygen deprivation can protect the myocardium from damage normally associated with a subsequent prolonged hypoxic/ischemic episode. However, is not known whether this potent mechanism of myocardial protection, termed preconditioning, exists in other vertebrates including fishes. In this study, we used an in situ trout (Oncorhynchus mykiss) working heart preparation at 10 degrees C to examine whether prior exposure to 5 min of anoxia (PO(2) < or = 5 mmHg) could reduce or eliminate the myocardial dysfunction that normally follows 15 min of anoxic exposure. Hearts were exposed either to a control treatment (oxygenated perfusion) or to one of three anoxic treatments: 1) anoxia with low P(out) [15 min of anoxia at an output pressure (P(out)) of 10 cmH(2)O]; 2) anoxia with high P(out) [10 min of anoxia at a P(out) of 10 cmH(2)O, followed by 5 min of anoxia at P(out) = 50 cmH(2)O]; and 3) preconditioning [5 min of anoxia at P(out) = 10 cmH(2)O, followed after 20 min of oxygenated perfusion by the protocol described for the anoxia with high P(out) group]. Changes in maximum cardiac function, measured before and after anoxic exposure, were used to assess myocardial damage. Maximum cardiac performance of the control group was unaffected by the experimental protocol, whereas 15 min of anoxia at low P(out) decreased maximum stroke volume (V(s max)) by 15% and maximum cardiac output (Q(max)) by 23%. When the anoxic workload was increased by raising P(out) to 50 cmH(2)O, these parameters were decreased further (by 23 and 38%, respectively). Preconditioning with anoxia completely prevented the reductions in V(s max) and Q(max) that were observed in the anoxia with high P(out) group and any anoxia-related increases in the input pressure (P(in)) required to maintain resting Q (16 ml. min(-1). kg(-1)). Myocardial levels of glycogen and lactate were not affected by any of the experimental treatments; however, lactate efflux was sevenfold higher in the preconditioned hearts. These data strongly suggest that 1) a preconditioning-like mechanism exists in the rainbow trout heart, 2) increased anaerobic glycolysis, fueled by exogenous glucose, was associated with anoxic preconditioning, and 3) preconditioning represents a fundamental mechanism of cardioprotection that appeared early in the evolution of vertebrates.
Asunto(s)
Corazón/fisiología , Hipoxia/fisiopatología , Precondicionamiento Isquémico Miocárdico , Oncorhynchus mykiss/fisiología , Análisis de Varianza , Animales , Glucógeno/metabolismo , Corazón/fisiopatología , Frecuencia Cardíaca , Lactatos/metabolismo , Modelos Cardiovasculares , Miocardio/metabolismo , Perfusión , Volumen SistólicoRESUMEN
In order to gain a better understanding of tissue plasticity with aging, we investigated the adaptive responses of young and adult animals to both 7 and 28 days of hypobaric hypoxia. Senescence is associated with a decreased tolerance to hypoxia that may be related to an age-associated decline in glucose transporter system plasticity. In addition, elucidation of the factors contributing to the decreased hypoxia tolerance with aging may provide insights into ischemia for older individuals. Following 7 days of hypobaric hypoxia, soleus and plantaris muscle Glut-4 contents were increased 23-45% with a greater increase in the soleus muscle for both ages. A parallel decline in insulin receptor content was observed in both the young (soleus 56%; plantaris 74%) and adult (soleus 26%; plantaris 37%) animals over 7 days. Similar responses were observed in cardiac muscle over 7 days, with increases in content for both Glut-4 (young 25%; adult 23%) and Glut-1 (young 33%; adult 44%) and a decline in insulin receptor (young 27%; adult 15%). Following 28 days of hypobaric hypoxia, adult soleus, and both age groups plantaris muscle Glut-4 and insulin receptor contents were similar to control. However, the young soleus muscle Glut-4 and insulin receptor contents were still significantly different from control but only altered about half as much as following 7 days of exposure to hypobaric hypoxia. In contrast to what was observed for skeletal muscle, cardiac Glut-4 content was further elevated in both young (33%) and adult (44%) animals with longer exposure to hypobaric hypoxia. The young animals also showed a further decrease in heart insulin receptor content, while the adult did not. Interestingly, cardiac Glut-1 levels returned to normal values for both young and adult animals with prolonged exposure. An adaptive coregulation of Glut-4 and insulin receptor content appears to optimize the use of glucose during chronic hypobaric hypoxia within these tissues. Differences are apparent in the magnitude and time course of the response between young and adult animals.
Asunto(s)
Envejecimiento/metabolismo , Proteínas de Transporte de Monosacáridos/metabolismo , Proteínas Musculares , Oxígeno/metabolismo , Animales , Peso Corporal , Enzimas/metabolismo , Femenino , Transportador de Glucosa de Tipo 1 , Transportador de Glucosa de Tipo 4 , Hipoxia , Músculo Esquelético/enzimología , Músculo Esquelético/patología , Miocardio/enzimología , Miocardio/patología , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
It was examined whether physical activity could alter the bioavailability of insulin-like growth factor-1 (IGF-1) which is dependent upon plasma IGF-1 and insulin-like growth factor binding protein (IGFBPs) levels. The potential role that growth hormone (GH) and insulin play in this process was also examined. Seven healthy 62-69-year-old women performed four bouts of physical activity on separate occasions at either a low (L; heart rate = 100 bpm) or moderate intensity (M; heart rate = 120 bpm) for either 25 (S) or 50 (L) min (LS, low intensity/short duration; LL, low intensity/long duration; MS, moderate intensity/short duration; ML, moderate intensity/long duration). GH levels were elevated immediately following the physical activity from 1.3 to 2.6-fold (P < 0.05) whereas IGF-1 levels were not affected by any activity condition. Plasma insulin levels decreased about 35% under all activity conditions (P < 0.05). Plasma levels of IGFBP-1 (BP-1) were decreased immediately following the ML (-47%; P < 0.05) and the LL (-21%) activity bouts and remained lower than initial values 1 h after these activity bouts (-25 and 34%, respectively, P < 0.05). The ML exercise bout resulted in significant (P < 0.05) increases in IGFBP-2 (BP-2) and IGFBP-3 (BP-3) immediately following activity (+31, and +30%, respectively) and these binding proteins remained elevated following the activity (+28, and +48%, respectively). No relationship was found between any changes in plasma GH or insulin, and changes in plasma IGFBPs. Thus, moderate intensity physical activity of long duration may modulate the bioavailability of IGF-1 in the elderly via alterations in BP-1, -2 and -3. However, changes in circulating levels of GH, insulin or IGF-1 do not appear to be regulating IGF-1 bioavailability in response to physical activity.
Asunto(s)
Envejecimiento/sangre , Ejercicio Físico/fisiología , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/análisis , Anciano , Pesos y Medidas Corporales , Femenino , Frecuencia Cardíaca , Hormona de Crecimiento Humana/sangre , Humanos , Hidrocortisona/sangre , Insulina/sangre , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Persona de Mediana Edad , Factores de TiempoRESUMEN
Phenytoin is a commonly used anticonvulsant drug for the prevention of seizures. A common side effect of phenytoin (PHT) therapy is connective tissue hyperplasia, particularly in the oral cavity manifesting as gingival overgrowth. Our previous studies concerning the molecular mechanisms of drug-induced gingival overgrowth have demonstrated that PHT alters the normal tissue turnover/wound healing signal by causing changes in macrophage phenotype, resulting in the upregulation of essential polypeptide growth factors such as platelet-derived growth factor (PDGF). The cellular consequences of this elevation in growth factor have not been investigated. The present light and electron microscopic study of rat hyperplastic connective tissue and human gingival overgrowth induced by PHT treatment revealed the presence of numerous myofibroblasts. Cells identified as myofibroblasts were evident in all PHT-treated tissue samples and were characterized by an elongated fusiform cell shape, abundant cytoplasmic rough endoplasmic reticulum/polyribosomes, and accumulations of sub-plasmalemmal microfilaments containing spindle densities. These cells were never observed in control tissues. Myofibroblasts are associated with the later stages of tissue turnover, specifically with the transition from the granulation to the remodeling phases of the wound healing process. The presence of myofibroblasts in hyperplastic connective and gingival tissues induced by PHT treatment suggests that PHT exacerbates the normal tissue turnover/wound healing signals responsible for the appearance of myofibroblasts.
Asunto(s)
Anticonvulsivantes/efectos adversos , Fibroblastos/efectos de los fármacos , Sobrecrecimiento Gingival/patología , Fenitoína/efectos adversos , Citoesqueleto de Actina/efectos de los fármacos , Adulto , Animales , Recuento de Células/efectos de los fármacos , División Celular/efectos de los fármacos , Tamaño de la Célula/efectos de los fármacos , Tejido Conectivo/efectos de los fármacos , Tejido Conectivo/patología , Retículo Endoplásmico Rugoso/efectos de los fármacos , Femenino , Fibroblastos/patología , Sobrecrecimiento Gingival/inducido químicamente , Tejido de Granulación/efectos de los fármacos , Tejido de Granulación/patología , Sustancias de Crecimiento/metabolismo , Humanos , Hiperplasia , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Microscopía Electrónica , Fenotipo , Factor de Crecimiento Derivado de Plaquetas/efectos de los fármacos , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Polirribosomas/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Regulación hacia Arriba/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacosRESUMEN
Phenytoin (pht) is an anticonvulsant drug commonly used for the prevention of seizures. A common side effect of PHT therapy is gingival hyperplasia, occasionally so severe that it requires surgical intervention. Cyclosporine A (CSA) is a drug widely used for the control of rejection phenomena following solid organ and bone marrow transplantation. A frequent side effect of CSA administration is gingival overgrowth. As yet, the molecular mechanisms of drug-induced gingival hyperplasia are unknown although it has been postulated that certain drugs increase fibroblastic activity through alterations in levels of various growth factors and cytokines. The purpose of this study was to: 1) evaluate monocyte/macrophage platelet-derived growth factor (PDGF) and interleukin (IL)-1 beta production in vitro after exposure to CSA; 2) determine the levels of PDGF-B and IL-1 beta gene expression in minimally inflamed gingival tissues of control patients and PHT-treated patients exhibiting gingival overgrowth as well as patients with severe gingival inflammation; and 3) combine characterization of macrophage phenotype with clinical presentation and expression of PDGF-B and IL-1 beta in gingival tissues from the control and PHT-treated patients. For the in vitro studies, commercial ELISA kits were used to measure PDGF-A/PDGF-B and IL-1 beta levels in conditioned media from rat and human monocyte/macrophage cell cultures. CSA caused a significant elevation of PDGF but did not cause any changes in IL-1 beta levels. For the in vivo studies, quantitative competitive reverse transcription polymerase chain reaction (QC-RTPCR) techniques were utilized to measure PDGF-B and IL-1 beta mRNA levels in experimental groups. PHT-treated patients exhibiting gingival overgrowth demonstrated a significant increase in PDGF-B mRNA compared with minimally inflamed controls. Patients with severe gingival inflammation also demonstrated a significant increase in PDGF-B mRNA however, PHT-induced PDGF-B upregulation is approximately 6 times larger than PDGF-B upregulation produced by inflammation alone. PHT-treated patients exhibiting gingival overgrowth demonstrated no significant increase in IL-1 beta mRNA; however, IL-1 beta mRNA levels in the severely inflamed gingival samples demonstrated a significant increase. Additionally, for the clinical samples, macrophage phenotype was characterized immunohistochemically in adjacent sections using specific monoclonal antibodies for inflammatory and reparative/proliferative phenotypes. There were no significant differences in the numbers of either macrophage phenotype in minimally inflamed gingival tissues; however, in the severely inflamed tissue, there was a significant increase in the inflammatory macrophage phenotype and in the hyperplastic gingival tissue, there was a significant increase in the reparative/proliferative macrophage phenotype. The results of this investigation indicate that the clinical presentation of inflamed and hyperplastic gingival tissues is associated with specific macrophages phenotypes which express the pro-inflammatory cytokine IL-1 beta in inflamed tissues or the essential polypeptide growth factor PDGF-B in PHT-induced hyperplastic tissues.
Asunto(s)
Anticonvulsivantes/toxicidad , Ciclosporina/toxicidad , Hiperplasia Gingival/inducido químicamente , Hiperplasia Gingival/metabolismo , Inmunosupresores/toxicidad , Interleucina-1/biosíntesis , Macrófagos/efectos de los fármacos , Fenitoína/toxicidad , Factor de Crecimiento Derivado de Plaquetas/biosíntesis , Adulto , Animales , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunofenotipificación , Macrófagos/inmunología , Macrófagos/metabolismo , Persona de Mediana Edad , ARN Mensajero/análisis , RatasRESUMEN
It has been proposed that healthy gingiva is in a continuous state of wound repair. Thus, one might expect to find cells in normal gingiva producing growth factors associated with wound healing such as platelet-derived growth factor B chain (PDGF-B). One might also expect to find increased numbers of these cells or increased amounts of these growth factors in conditions which involve increased tissue volume such as drug-induced gingival overgrowth (DGO). The purpose of this study was to quantify PDGF-B gene expression and identify cells producing PDGF-B in normal gingiva and DGO. Cyclosporine A (CSA) was selected as a prototype of the overgrowth condition. Twelve patients with clinical CSA DGO and 12 patients with no DGO or history of drugs known to cause DGO were selected for study. Frozen sections of gingival specimens from these patients were subjected to in situ hybridization for PDGF-B mRNA. Positive cells were counted and expressed as mean +/- SEM cells/mm2 of lamina propria. Morphometric analysis revealed 6.2 +/- 1.9 cells/mm2 for control gingiva and 10.3 +/- 3.4 cells/mm2 for CSA DGO samples. There was no statistically significant difference between groups. PDGF-B gene expression was measured in these cells and expressed as mean +/- SEM silver grains/cells. There was a significant upregulation of PDGF-B gene expression in cells from the CSA DGO group (39.5 +/- 14.7 silver grains/cell for normal gingiva vs. 255.3 +/- 77.1 silver grains/cell for CSA DGO samples; P < 0.001). The presence of PDGF-B in these cells was confirmed in all cases by immunocytochemical localization. Additionally, PDGF-B producing cells were identified as macrophages in sections taken from an additional patient with CSA DGO by double immunofluorescence labeling of the CD51 membrane marker for macrophages and intracellular PDGF-B. These findings are consistent with the concept that healthy gingiva is in a continuous state of wound repair and support the hypothesis that CSA DGO is associated with enhanced macrophage PDGF-B gene expression rather than an increase in the number of PDGF-B producing macrophages.
Asunto(s)
Ciclosporina/efectos adversos , Encía/metabolismo , Hiperplasia Gingival/metabolismo , Inmunosupresores/efectos adversos , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Becaplermina , Colorantes , Técnica del Anticuerpo Fluorescente Directa , Secciones por Congelación , Regulación de la Expresión Génica/efectos de los fármacos , Encía/patología , Hiperplasia Gingival/inducido químicamente , Hiperplasia Gingival/patología , Humanos , Inmunohistoquímica , Hibridación in Situ , Integrina alfaV , Integrinas/genética , Integrinas/metabolismo , Macrófagos/metabolismo , Macrófagos/patología , Factor de Crecimiento Derivado de Plaquetas/genética , Proteínas Proto-Oncogénicas c-sis , Plata , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/genética , Cicatrización de Heridas/genéticaRESUMEN
Cyclosporine A (CSA) is a widely used immunosuppressant for transplant patients and is also used for the treatment of a wide variety of systemic diseases with immunologic components. A prominent side effect of CSA administration is gingival overgrowth (hyperplasia). It has been postulated that CSA alters fibroblast activity through effects on various growth factors/cytokines. However, as yet, data concerning the molecular mechanisms involved in pathologic connective tissue proliferation are preliminary in nature. Our previous investigations concerning phenytoin-induced effects on platelet-derived growth factor B (PDGF-B) gene expression have demonstrated that other drugs which cause gingival overgrowth can upregulate macrophage PDGF-B gene expression in vitro and in vivo. The purpose of the present study was to evaluate PDGF-B gene expression in gingival tissues of patients receiving CSA therapy and exhibiting gingival overgrowth to determine if similar PDGF-B upregulation occurs in response to CSA and to identify PDGF-B producing cells in these tissues. Quantitative competitive reverse transcription polymerase chain reaction (QC-RTPCR) techniques were utilized to measure PDGF-B mRNA levels in CSA overgrowth patients and normal controls (N = 6/group). Results were expressed as mean +/- mRNA copy number and tested for significance using unpaired t-tests. Gingival samples were harvested (standardized for local inflammation at the sample site), total RNA was extracted, and QC-RTPCR was performed using specific PDGF-B primers and a corresponding competitive internal standard. CSA-treated patients exhibiting gingival overgrowth demonstrated approximately 48-fold increase in PDGF-B mRNA (7667.1 +/- 477.4 copies for CSA patients vs. 158.2 +/- 37.1 copies for controls; P < 0.001). Additionally, dual fluorescence immunohistochemistry for mature macrophage marker antigen (CD51) and intracellular PDGF-B was utilized to identify and localize PDGF-B producing cells were demonstrated to be macrophages distributed in a non-uniform manner throughout the papillary connective tissue. These results further support the hypothesis that the molecular mechanisms responsible for drug-induced gingival overgrowth may involve upregulation of PDGF-B macrophage gene expression. We continue to investigated specific CSA-induced alterations of macrophage PDGF-B gene expression in vitro and in vivo.
Asunto(s)
Ciclosporina/efectos adversos , Hiperplasia Gingival/metabolismo , Inmunosupresores/efectos adversos , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Adulto , Antígenos CD/genética , Antígenos CD/metabolismo , Becaplermina , Tejido Conectivo/metabolismo , Tejido Conectivo/patología , Técnica del Anticuerpo Fluorescente Directa , Regulación de la Expresión Génica/efectos de los fármacos , Hiperplasia Gingival/inducido químicamente , Hiperplasia Gingival/patología , Humanos , Integrina alfaV , Integrinas/genética , Integrinas/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Persona de Mediana Edad , Factor de Crecimiento Derivado de Plaquetas/genética , Reacción en Cadena de la Polimerasa , Proteínas Proto-Oncogénicas c-sis , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transcripción Genética , Regulación hacia Arriba/genéticaRESUMEN
Delayed wound healing is a troublesome complication of Diabetes. Results from recent investigations concerning the potential cellular and molecular mechanisms responsible for diabetic wound healing deficiency are preliminary in nature. Some studies have demonstrated that direct application of certain growth factors/cytokines can facilitate wound healing in diabetic models. It is possible that refractory diabetic wounds are the result of deficiencies in growth factors/cytokines important for the normal wound healing process. Platelet-Derived Growth Factor (PDGF) levels were examined by radioimmunoassay in wound tissue of normal and diabetic rats (streptozotocin-induced diabetes). Immunohistochemical analysis was utilized to localize and characterize PDGF immunopositive cells at the wound site of normal and diabetic animals. At the wound site, normal animals demonstrated significantly elevated PDGF levels compared to diabetic animals at 5 days post-wounding (no differences were observed in the spleen or contralateral control tissue). There appeared to be a visible increase in PDGF immunopositive cells at the wound site in both experimental and control groups. By day 10 post-wounding, PDGF levels at the wound site in normal animals were reduced becoming similar to PDGF levels in diabetic animals. This corresponded to an apparent reduction of PDGF immunopositive cells in both groups (similar to baseline levels). PDGF levels in both groups remained stable until day 20 post-wounding when a significant elevation of wound site PDGF levels occurred in the diabetic group. The findings suggest that absence of an initial increase in PDGF may play an important role in poor wound healing observed in diabetic animals. The reduction in PDGF may be related to decreased cellular PDGF production rather than a lack of PDGF-producing cells. Perhaps the diabetic state inhibits cellular PDGF gene expression signaled by wounding or interferes with normal PDGF expression at the wound site.
Asunto(s)
Diabetes Mellitus Experimental/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Cicatrización de Heridas , Animales , Técnicas Inmunológicas , Insulina/farmacología , Masculino , Ratas , Ratas Sprague-Dawley , Bazo/metabolismo , Factores de TiempoRESUMEN
A population of cells in the spleens of normal rats was found to contain platelet-derived growth factor (PDGF) B chain mRNA. These cells were found predominantly in the red pulp and nuclear morphology of some was consistent with that of macrophages. Similar cells were also shown by immunocytochemical staining to contain PDGF-AB/BB. These PDGF-positive cells were also found almost exclusively in the red pulp. It has been suggested by others that PDGF plays an important role in the function of the lymphohemopoietic microenvironment.
Asunto(s)
Factor de Crecimiento Derivado de Plaquetas/metabolismo , Bazo/metabolismo , Animales , Inmunohistoquímica , Hibridación in Situ , Masculino , Factor de Crecimiento Derivado de Plaquetas/genética , ARN Mensajero/análisis , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Bazo/química , Bazo/citologíaRESUMEN
The mechanism by which phenytoin (PHT) induces gingival overgrowth remains unclear. We hypothesized that PHT increases macrophage production of platelet-derived growth factor (PDGF), an important cytokine in connective tissue growth and repair, and that excessive production PDGF in gingiva could lead to redundant growth. To test the hypothesis, rat peritoneal macrophages and human blood monocytes were cultured in the presence of PHT (5 to 20 micrograms/ml medium) or an equal volume of its solvent for 3 days and tested for expression of PDGF-B mRNA by in situ hybridization. Approximately 300 cells/culture well were examined (3 wells/drug level) for positive indication of PDGF-B mRNA. Data were compared by chi square test. All levels of PHT in both cell types induced a 2- to 8-fold increase in PDGF-B mRNA positive cells, significant in all cases at P < 0.001. Northern blot analysis of RNA from similarly cultured rat macrophages confirmed these findings. Cells treated with 10 micrograms PHT/ml medium or solvent revealed 2.2 +/- 0.3 and 1.0 +/- 0.2 (mean +/- SEM) arbitrary units PDGF mRNA respectively (t tests, P < 0.05). Additionally, rat macrophages were cultured in presence of 5 micrograms PHT/medium or its solvent and medium was analyzed for PDGF secretion by radioimmunoassay. Mean values (+/- SEM) were 1.28 +/- 0.49 and 0.78 +/- 0.07 ng/mg protein respectively (t test, P < 0.05). These data showed that PHT augmented the expression of c-sis, the gene for PDGF-B, and offered a possible explanation for PHT-induced gingival overgrowth.
Asunto(s)
Expresión Génica/efectos de los fármacos , Macrófagos/efectos de los fármacos , Fenitoína/farmacología , Factor de Crecimiento Derivado de Plaquetas/genética , Proteínas Proto-Oncogénicas/genética , Animales , Northern Blotting , Distribución de Chi-Cuadrado , Humanos , Hibridación in Situ , Activación de Macrófagos , Macrófagos/metabolismo , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Sondas de Oligonucleótidos , Factor de Crecimiento Derivado de Plaquetas/biosíntesis , Proteínas Proto-Oncogénicas/biosíntesis , Proteínas Proto-Oncogénicas c-sis , ARN Mensajero/análisis , Radioinmunoensayo , Ratas , Transcripción Genética/efectos de los fármacosRESUMEN
An overview of surface acoustic wave (SAW) filter techniques available for different applications is given. Techniques for TV IF applications are outlined, and typical structures are presented. This is followed by a discussion of applications for SAW resonators. Low-loss devices for mobile communication systems and pager applications are examined. Tapped delay lines (matched filters) and convolvers for code-division multiaccess (CDMA) systems are also covered. Although simulation procedures are not considered, for many devices the theoretical frequency response is presented along with the measurement curve.
RESUMEN
Culture of L-929 fibroblasts in the presence of phenytoin (2.5-5.0 micrograms/ml) increased DNA synthesis, as indicated by increased [3H]thymidine uptake, while a higher dose (20 micrograms/ml) inhibited DNA synthesis. In like manner, a low dose of phenytoin (5.0 micrograms/ml) was effective in increasing inositol 1,4,5-trisphosphate formation while a higher dose (10 micrograms/ml) tended to inhibit this activity. These data suggest that the formation of inositol phosphate second messengers may play a role in phenytoin-induced fibroblast proliferation and connective tissue growth.
Asunto(s)
ADN/biosíntesis , Fibroblastos/metabolismo , Inositol 1,4,5-Trifosfato/biosíntesis , Fenitoína/farmacología , Bombesina/farmacología , Células Cultivadas , Timidina/metabolismoRESUMEN
Daptomycin (LY 146032), a new lipopeptide antimicrobial agent with activity against gram-positive bacteria, was compared to vancomycin in the treatment of staphylococcal bacteremia in a murine model. Two hundred and ninety-nine mice were inoculated with 1 x 10(8) bacteria by the tail vein, and treatment was begun 3 days later. Two dosage regimens of each drug were used: 10 mg/kg and 5 mg/kg administered every 12 h for 14 days. A control group received no therapy. Survival was determined 31 days after inoculation. There was no significant difference in survival in any of the four treatment groups. The survival in all treatment groups was significantly greater than in the control group. Serum levels of daptomycin remained longer in the therapeutic range than serum levels of vancomycin. In the murine model of staphylococcal disease, daptomycin treatment was as effective as treatment with vancomycin.
Asunto(s)
Sepsis/tratamiento farmacológico , Infecciones Estafilocócicas/tratamiento farmacológico , Vancomicina/uso terapéutico , Animales , Daptomicina , Femenino , Ratones , Pruebas de Sensibilidad Microbiana , Péptidos/sangre , Péptidos/uso terapéutico , Infecciones Estafilocócicas/etiología , Vancomicina/sangreRESUMEN
The i.p. injection of 3-methoxybenzamide (3-MBA) in rats produces a dose-related elevation of the threshold for response to a painful stimulus. Metoclopramide, also a substituted benzamide, has analgesic activity that is attenuated by bromocriptine, a dopamine receptor agonist, and by the narcotic antagonist, naloxone, suggesting involvement of dopamine and opiate receptors in the action of this drug. The involvement of these receptors in the analgesic action of 3-MBA has been examined using L-dopa and naloxone. Neither significantly altered the analgesic action. Although the results are preliminary, the analgesic action of 3-MBA would not seem to occur via opiate or dopamine receptors.
Asunto(s)
Analgésicos , Benzamidas/farmacología , Animales , Conducta Animal/efectos de los fármacos , Levodopa/farmacología , Masculino , Naloxona/farmacología , Ratas , Ratas Endogámicas , Receptores Dopaminérgicos/efectos de los fármacos , Receptores Opioides/efectos de los fármacos , Factores de TiempoRESUMEN
This study demonstrates that, in rats, systemically administered phenytoin produces a statistically significant increase in accumulation of phagocytic and esterase positive cells in areas of phenytoin-induced connective tissue proliferation. Many of these cells are perceived to be macrophages. Since macrophages have been shown to produce chemoattractant and mitogens for fibroblasts, they may very well play a major role in the gingival hyperplasia seen in patients taking phenytoin. The results of the study show that the effects of phenytoin on fibroblasts may be more complex than previously thought.
Asunto(s)
Tejido Conectivo/patología , Macrófagos/patología , Animales , Recuento de Células , Esterasas/análisis , Hiperplasia/inducido químicamente , Hiperplasia/patología , Macrófagos/enzimología , Fagocitos/patología , Fagocitosis , Fenitoína , Ratas , Ratas EndogámicasRESUMEN
Rats were treated daily for 9 days with 100, 50, or 25 mg/kg phenytoin i.p. This treatment resulted in a significant increase in the thickness of the connective tissue capsules of the liver, spleen, and pancreas, and of the subepithelial connective tissue of the mesentery but not the epicardium or visceral pleura of the lung where exposure to the drug was via the vascular route. Many areas of connective tissue growth exhibited obvious proliferation of fibroblasts and in some areas contained seemingly large numbers of macrophages and an increase in vascularity. It was demonstrated by electron microscopy that the macrophages occasionally were seen in intimate contact with the fibroblasts. Our observations clearly showed that intraperitoneal exposure of visceral connective tissues of the rat to phenytoin rapidly resulted in a dose-related proliferation of that tissue. The presence of numerous macrophages leads to the suggestion that macrophage-derived growth factor could be responsible for the increased growth.
Asunto(s)
Tejido Conectivo/fisiología , Fenitoína/farmacología , Animales , División Celular/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Tejido Conectivo/efectos de los fármacos , Tejido Conectivo/ultraestructura , Relación Dosis-Respuesta a Droga , Fibroblastos/citología , Crecimiento/efectos de los fármacos , Masculino , Microscopía Electrónica , RatasRESUMEN
Ascorbic acid was examined for potentiative effects on the catalepsy induced by haloperidol in rats and squirrel monkeys. In both animal species pretreatment with ascorbic acid (1000 mg/kg) markedly potentiated catalepsy induced by haloperidol. It is suggested that vitamin binds to, and inactivates, some brain dopamine receptors and in so doing potentiates an otherwise minimally cataleptogenic dose of haloperidol.
Asunto(s)
Ácido Ascórbico/farmacología , Catalepsia/inducido químicamente , Haloperidol/farmacología , Animales , Sinergismo Farmacológico , Femenino , Masculino , Ratas , Ratas Endogámicas , Saimiri , Factores de TiempoRESUMEN
The application of a thin oxide film is seen as a method of improving the ceramic-to-metal bond. Using sputter coating to form oxide films allows control of its thickness. The thickness of the oxide layer can also be controlled by sputter coating. Films produced by sputtering, in themselves, have superior bond strengths in that the high-energy levels that are used in the technique drive the coating material into the atomic lattice of the substrate material (dental gold). Remaining to be determined are optimum film thickness and the oxide to be used. However, the present study opens a field of study showing promise of improving porcelain-to-metal bonding in dental restoration.
Asunto(s)
Aleaciones Dentales , Recubrimiento Dental Adhesivo/métodos , Porcelana Dental , Óxidos , Compuestos de Estaño , Adhesividad , Óxido de Aluminio , Indio , Propiedades de Superficie , EstañoRESUMEN
An activity cage has been designed to provide a quantitative measure of locomotor activity in small primates. Movement is detected by the interruptions of photocell beams, which are counted electronically and stored in on-board memory for subsequent display or entry into a computer. The device functions independently, and does not require a computer to be on-line during data collection. Data thus obtained have proven reliable, and are a valid record of the activity of the animal.
Asunto(s)
Monitoreo Fisiológico/instrumentación , Actividad Motora , Animales , Luz , Actividad Motora/efectos de los fármacos , SaimiriRESUMEN
Locomotor activity of ten squirrel monkeys, Saimiri sciureus, was evaluated by means of a photocell activity cage following intracranial application of dopamine (DA). A biphasic response consisting of an initial quiet period followed by increased locomotor activity was seen following intra-accumbens DA, 12.5--100 micrograms bilaterally. Both the length of the quiet phase and intensity of locomotor activity were positively related to DA dose. Intra-caudate DA (50 micrograms) was significantly less effective in producing locomotor effects. The specificity of the DA response was substantiated by dose-related inhibition with both systemic (0.1 or 0.05 mg/kg) and intra-accumbens (2--10 micrograms) administration of the DA antagonist haloperidol. Additionally, the intra-accumbens application of haloperidol was found to be ineffective in inducing catalepsy, a state readily produced by systemically administered haloperidol.