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OBJECTIVE: Clinical observations have shown an accelerated wound healing in wounds of patients treated by Vacuum Assisted Closure (V.A.C.)-therapy. The mechanisms of improved wound healing on cellular level have been hitherto less investigated. In this study the levels of proinflammatory interleukins (IL-6, IL-8, IL-10) and growth factors (VEGF, FGF-2) in serum and wound were monitored. METHODS: The study included 21 patients with traumatic wounds that could not be closed during the first surgical intervention. The soft tissue defects (n = 21) were closed temporarily by Epigard. During the first second-look operation after 2.0 +/- 0.2 days in an average, Epigard was used for another 2.5 +/- 0.4 days as temporary soft tissue coverage in 13 patients (group A). In the remaining 8 patients the wound conditioning was done by V.A.C.(R) for 2.4 +/- 0.3 days (group B). A total of 428 samples of serum and wound fluid samples were collected during the first and second look operation. Levels of IL-6, IL-8, IL-10, VEGF and FGF were measured specific by ELISA. RESULTS: In all interleukins and growth factors there were significant lower serum level concentrations compared with those in wound fluids. During the first temporary dressing change after wound coverage with Epigard the wound samples showed the following levels [Mean (SEM)]: IL-6 49 816 (19 889) pg/ml, IL-8 54 (16) ng/ml, IL-10 314 (44) pg/ml, VEGF 4 746 (766) pg/ml, FGF-2 494 (89) pg/ml. During the second dressing changes we monitored the following levels in group A: IL-6 7 218 (2 542) pg/ml, IL-8 69 (27) ng/ml, IL-10 261 (58) pg/ml, VEGF 3 551 (661) pg/ml, FGF-2 355 (67) pg/ml. In group B the samples of the wound fluid showed the following results: IL-6 16 966 (4 124) pg/ml [p = 0.02], IL-8 223 (91) ng/ml [p = 0.03], IL-10 233 (76) pg/ml [p = 0.38], VEGF 7 490 (1 565) pg/ml [p = 0.01], FGF-2 352 (43) pg/ml [p = 0.48]. CONCLUSION: The increased local release of IL-6, IL-8 and VEGF in wounds after V.A.C.-therapy may be involved in the accumulation of neutrophil granulocytes and angiogenesis, which seams to play a crucial role for the accelerated granulation tissue formation after V.A.C.-therapy compared to wounds treated by Epigard.
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Factor 2 de Crecimiento de Fibroblastos/sangre , Interleucina-10/sangre , Interleucina-6/sangre , Interleucina-8/sangre , Apósitos Oclusivos , Traumatismos de los Tejidos Blandos/cirugía , Factor A de Crecimiento Endotelial Vascular/sangre , Síndromes Compartimentales/inmunología , Síndromes Compartimentales/cirugía , Desbridamiento , Líquido Extracelular/inmunología , Polímeros de Fluorocarbono , Fracturas Abiertas/inmunología , Fracturas Abiertas/cirugía , Humanos , Reoperación , Traumatismos de los Tejidos Blandos/inmunología , Técnicas de Sutura , VacioRESUMEN
Loss of neurons after traumatic brain injury (TBI) might involve dysregulated apoptosis. Activation of caspase-3 is one hallmark of apoptosis. Therefore, caspase-3 activity (cleavage of DEVD-afc) was measured in cerebrospinal fluid (CSF) samples (n=113) from 27 patients with TBI at day 1 to 14 after trauma. Caspase-3 activity was detected in 31 (27.4%) CSF samples with highest values (> 5.5 microM/min) seen at day 2-5 after trauma. No caspase-3 activity was found in serum from patients or CSF from controls. The presence of activated caspase-3 in CSF suggests ongoing apoptotic processes during traumatic brain injury.
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Lesiones Encefálicas/líquido cefalorraquídeo , Lesiones Encefálicas/enzimología , Caspasas/líquido cefalorraquídeo , Adulto , Apoptosis/fisiología , Lesiones Encefálicas/patología , Caspasa 3 , Cumarinas , Activación Enzimática , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronas/metabolismo , Neuronas/patología , OligopéptidosRESUMEN
BACKGROUND: The influence of caspase inhibitors on spontaneous and on CD95-triggered apoptosis was investigated in neutrophils from healthy volunteers and compared with neutrophils from patients with severe sepsis. METHODS: To further elucidate the mechanisms of neutrophil apoptosis, isolated neutrophils from healthy volunteers (n = 9) were either stimulated with the agonistic anti-CD95 antibody (100 ng/mL) or left unstimulated in the presence or absence of the caspase inhibitors zIETD-fmk (10 micromol/L), zDEVD-fmk (10 micromol/L), or zVAD-fmk (20 micromol/L). Apoptosis was determined by measuring DNA fragmentation and Annexin-V binding in FACS, and caspase-3-like activity by DEVD-afc cleavage assay. Results were compared with those from patients with severe sepsis (n = 15). RESULTS: Reduced spontaneous neutrophil apoptosis in patients with sepsis (-48.7%) was completely restored by incubation with agonistic anti-CD95 antibody (p < 0.05). Inhibition of caspases did not influence spontaneous neutrophil apoptosis in both groups. However, zVAD-fmk reduced anti-CD95 antibody-induced apoptosis in neutrophils from controls by -22.6% (p < 0.05) and in patients with sepsis by -43.1% (p < 0.05). CONCLUSION: These results indicate that spontaneous in contrast to CD95-induced neutrophil apoptosis is independent of caspase activity.
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Apoptosis , Caspasas/metabolismo , Neutrófilos/patología , Sepsis/metabolismo , Clorometilcetonas de Aminoácidos/farmacología , Estudios de Casos y Controles , Inhibidores de Cisteína Proteinasa/farmacología , Activación Enzimática , Humanos , Neutrófilos/metabolismo , Sepsis/inmunología , Receptor fas/metabolismoRESUMEN
The study objective was to analyze hazardous materials event and victim factors associated with transportation of victims to a health care facility, and evacuation or shelter-in-place of nearby populations. A retrospective review was conducted on hazardous materials events in Washington State from 1993 to 1997. Bivariate and multiple logistic regression were used to identify risk factors for transportation, evacuation, and shelter-in-place. Over five years, 2,654 victims from 457 events were reported, with 1,859 (70%) transported to a health care facility. Evacuation occurred in 279 (61%) events and shelter-in-place in 14 (3%) events. After excluding 14 deaths, regression analysis indicated that victims with trauma (OR 5.87, 95% CI 1.41-24.5), thermal burns (6.90, 1.15-41.3), dizziness/other CNS symptoms (1.59, 1.00-2.54), and headache (1.54, 1.01-2.35) were most likely to be transported. Chemical releases inside buildings (2.09, 1.06-4.10, compared with transportation events), and involving 3-5 victims (2.86, 1.54-5.31, compared to 1 victim) or > or =6 victims (8.74, 4.01-19.0), were most likely to involve evacuation or shelter-in-place. Events involving sulfuric acid (0.15, 0.05-0.49) and sodium hydroxide (0.19, 0.04-0.94) were least likely to involve evacuation or shelter-in-place. Prehospital decisions to transport victims to a health care facility and evacuate or shelter-in-place nearby populations are associated with event and victim factors. Further research is needed to determine if these factors also predict need for medical care or removal from exposure, and to develop evidence-based prehospital care protocols for hazardous materials exposure victims.
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Planificación en Desastres , Servicio de Urgencia en Hospital/organización & administración , Sustancias Peligrosas , Trabajo de Rescate/organización & administración , Transporte de Pacientes , Adolescente , Adulto , Anciano , Niño , Preescolar , Toma de Decisiones , Femenino , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Washingtón/epidemiología , Heridas y Lesiones/epidemiologíaRESUMEN
In lipopolysaccharide-stimulated blood from 71 late-stage borreliosis patients, the ex vivo cytokine release capacity of tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) was reduced to 28% +/- 5% and to 31% +/- 5% (P < or = 0.001), respectively, compared to that of 24 healthy controls. White blood cell counts were normal in both groups. To investigate direct interactions between the pathogen and the immune cells, blood from healthy controls was exposed in vitro to live or heat-killed Borrelia or to Borrelia lysate. Compared to the pattern induced by bacterial endotoxins, a reduced release of TNF-alpha and IFN-gamma and an enhanced secretion of interleukin-10 and granulocyte colony-stimulating factor was found. In blood from 10 borreliosis patients stimulated with Borrelia lysate, TNF-alpha formation was decreased to 31% +/- 14% and IFN-gamma formation was decreased to 8% +/- 3% (P < or = 0.001) compared to the cytokine response of blood from healthy controls (n = 24). We propose to consider anti-inflammatory changes in the blood cytokine response capacity elicited by Borrelia as a condition that might favor the persistence of the spirochete.
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Citocinas/sangre , Enfermedad de Lyme/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Grupo Borrelia Burgdorferi/inmunología , Femenino , Factor Estimulante de Colonias de Granulocitos/sangre , Humanos , Interferón gamma/sangre , Interleucina-10/sangre , Lipopolisacáridos/toxicidad , Masculino , Persona de Mediana Edad , Factor de Necrosis Tumoral alfa/análisisRESUMEN
Using a Burkean framework (1969), this article approaches medical dramas as cultural texts to be read for dominant meanings of health and health care. Burke's representative anecdote illuminates the melding of science, technology, and healing in popular discourses of health, establishing technological intervention as the norm and marginalizing nontechnological (i.e., alternative) forms of health care. Popular entertainment reinforces this anecdote in narratives of healing as technological competence triumphing over nature.
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Terapias Complementarias , Drama , Ciencia del Laboratorio Clínico , Filosofía Médica , Televisión , Anécdotas como Asunto , Competencia Clínica , Humanos , Medios de Comunicación de Masas , Naturaleza , Estados UnidosRESUMEN
The interleukins (IL)-1beta and IL-18 represent potent players in the proinflammatory cytokine cascade. Their activation is regulated predominantly through the IL-1-converting enzyme (ICE)/caspase-1. The role of caspases in the secretion of IL-1beta and IL-18, as well as in the release of the secondary-induced cytokines IL-12 and interferon (IFN)-gamma in whole blood from septic patients compared to healthy controls, was studied. Inhibition of caspase activity by Z-VAD significantly reduced lipopolysaccharide (LPS) and Staphylococcus aureus (SAC) induced release of mature IL-1beta in septic patients and controls. In contrast, in whole blood from septic patients significantly elevated basal level of IL-18 were found, which could neither be further increased by LPS or SAC, nor be inhibited by Z-VAD. Release of IL-12 p40 was significantly lower in septic patients compared to controls and was not affected by Z-VAD. Despite high levels of IL-18, IFN-gamma was not detected in whole blood from septic patients even after stimulation with SAC or LPS. Thus, during sepsis, caspases participate in the processing of IL-1beta, whereas maturation of IL-18 during sepsis appears to be independent of caspases. The lack of IFN-gamma release seen in septic patients could be attributed to low IL-12 release rather than to diminished IL-18 release.
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Inhibidores de Caspasas , Citocinas/sangre , Sepsis/enzimología , Sepsis/inmunología , Adulto , Clorometilcetonas de Aminoácidos/farmacología , Estudios de Casos y Controles , Inhibidores de Cisteína Proteinasa/farmacología , Citocinas/efectos de los fármacos , Femenino , Humanos , Interferón gamma/sangre , Interferón gamma/efectos de los fármacos , Interleucina-1/sangre , Interleucina-12/sangre , Interleucina-18/sangre , Lipopolisacáridos/farmacología , Masculino , Persona de Mediana Edad , Sepsis/microbiología , Staphylococcus aureusRESUMEN
Identifying industries at high risk for hazardous materials releases can facilitate prevention and preparation for such events. A retrospective review by Standard Industrial Classification (SIC) codes was conducted on non-petroleum hazardous materials emergency events from 1993 to 1995 and collected by the Washington State Department of Health in a program supported by the Agency for Toxic Substances and Disease Registry. Annual US Census data were used to determine the number of facilities and employees by SIC code in the state of Washington. SIC codes with the most total events and events per 10,000 employees were ranked and characterized by type of releases. In 3 years, 1269 events were recorded, with 294 involving human victims. Industries with the highest average annual number of events per 10,000 employees were agricultural chemical manufacturing (142); petroleum refining (122); industrial and miscellaneous chemical manufacturing (56); electric light and power (54); and pulp, paper, and paperboard mills (39). Industries with high rates of hazardous materials emergency events should continue to develop methods of preventing these releases.
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Contaminación Ambiental/estadística & datos numéricos , Sustancias Peligrosas/envenenamiento , Industrias , Urgencias Médicas , Humanos , WashingtónRESUMEN
An early cellular response of osteoblasts to swelling is plasma membrane depolarization, accompanied by a transient increase in intracellular calcium ([Ca2+]i), which initiates regulatory volume decrease (RVD). The authors have previously demonstrated a hypotonically induced depolarization of the osteoblast plasma membrane, sufficient to open L-type Ca channels and mediate Ca2+ influx. Herein is described the initiation of RVD in UMR-106.01 cells, mediated by hypotonically induced [Ca2+]i transients resulting from the activation of specific isoforms of L-type Ca channels. The authors further demonstrate that substrate interaction determines which specific alpha1 Ca channel subunit isoform predominates and mediates Ca2+ entry and RVD. Swelling-induced [Ca2+]i transients, and RVD in cells grown on a type I collagen matrix, are inhibited by removal of Ca from extracellular solutions, dihydropyridines, and antisense oligodeoxynucleotides directed exclusively to the alpha1C isoform of the L-type Ca channel. Ca2+ transients and RVD in cells grown on untreated glass cover slips were inhibited by similar maneuvers, but only by antisense oligodeoxynucleotides directed to the alpha1S isoform of the L-type Ca channel. This represents the first molecular identification of the Ca channels that transduce the initiation signal for RVD by osteoblastic cells.
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Neoplasias Óseas/metabolismo , Canales de Calcio/metabolismo , Osteosarcoma/metabolismo , Animales , Neoplasias Óseas/patología , Calcio/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo L , Tamaño de la Célula/efectos de los fármacos , Tamaño de la Célula/fisiología , Dihidropiridinas/farmacología , Soluciones Hipotónicas/farmacología , Nifedipino/farmacología , Oligonucleótidos Antisentido/metabolismo , Concentración Osmolar , Osteoblastos/metabolismo , Osteoblastos/patología , Técnicas de Placa-Clamp , Isoformas de Proteínas , Ratas , Células Tumorales CultivadasRESUMEN
The up-regulation of the inducible nitric oxide synthase (iNOS) mRNA was determined by RT-PCR in 25 tissues each from 22 specific pathogen-free (SPF) dogs experimentally infected with Borrelia burgdorferi by tick exposure and from five uninfected control dogs. Using primers specific for a homologous region of the human and canine iNOS sequence, and canine macrophage mRNA, we isolated and partially sequenced canine iNOS. A sequence of 1775 bases was obtained and primers specific for canine iNOS mRNA constructed to investigate the expression of iNOS in dog tissues in response to infection with B. burgdorferi. In 12 out of 22 dogs infected with B. burgdorferi, acute lameness occurred within 55-82 days after infection whereas the other 10 dogs showed no or only mild clinical signs despite persistent infection up to Day 175. The numbers of iNOS mRNA-positive tissues in dogs with acute lameness were significantly higher than in dogs without lameness, while uninfected dogs showed only negligible iNOS expression. Dogs with acute lameness also had higher numbers of borrelia-positive tissues as well as higher scores in histopathological evaluations than infected dogs without lameness. Our results show that the expression of iNOS mRNA is related to the number of B. burgdorferi-positive tissues and the severity of inflammation as assessed by histopathology. These results implicate an up-regulation of the iNOS mRNA as part of the host's immune response to borrelia infection and a possible role for NO in the pathogenesis of canine Lyme arthritis.
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Enfermedades de los Perros/enzimología , Enfermedad de Lyme/veterinaria , Óxido Nítrico Sintasa/genética , ARN Mensajero/biosíntesis , Regulación hacia Arriba , Animales , Artritis Infecciosa/enzimología , Artritis Infecciosa/patología , Artritis Infecciosa/veterinaria , Grupo Borrelia Burgdorferi/aislamiento & purificación , Enfermedades de los Perros/patología , Perros , Femenino , Humanos , Articulaciones/patología , Cojera Animal/enzimología , Cojera Animal/microbiología , Cojera Animal/patología , Enfermedad de Lyme/enzimología , Enfermedad de Lyme/patología , Macrófagos Alveolares/enzimología , Masculino , Datos de Secuencia Molecular , Óxido Nítrico Sintasa/biosíntesis , Óxido Nítrico Sintasa de Tipo II , Reacción en Cadena de la Polimerasa/veterinaria , ARN Mensajero/químicaRESUMEN
Canine synovial membrane explants were exposed to high- or low-passage Borrelia burgdorferi for 3, 6, 12, and 24 h. Spirochetes received no treatment, were UV light irradiated for 16 h, or were sonicated prior to addition to synovial explant cultures. In explant tissues, mRNA levels for the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), IL-1beta, and IL-8 were surveyed semiquantitatively by reverse transcription-PCR. Culture supernatants were examined for numbers of total and motile (i.e., viable) spirochetes, TNF-like and IL-1-like activities, polymorphonuclear neutrophil (PMN) chemotaxis-inducing activities, and IL-8. During exposure to synovial explant tissues, the total number of spirochetes in the supernatants decreased gradually by approximately 30%, and the viability also declined. mRNAs for TNF-alpha, IL-1alpha, IL-1beta, and IL-8 were up-regulated in synovial explant tissues within 3 h after infection with untreated or UV light-irradiated B. burgdorferi, and mRNA levels corresponded to the results obtained with bioassays. During 24 h of coincubation, cultures challenged with untreated or UV light-irradiated spirochetes produced similar levels of TNF-like and IL-1-like activities. In contrast, explant tissues exposed to untreated B. burgdorferi generated significantly higher levels of chemotactic factors after 24 h of incubation than did explant tissues exposed to UV light-treated spirochetes. In identical samples, a specific signal for IL-8 was identified by Western blot analysis. High- and low-passage borreliae did not differ in their abilities to induce proinflammatory cytokines. No difference in cytokine induction between untreated and sonicated high-passage spirochetes was observed, suggesting that fractions of the organism can trigger the production and release of inflammatory mediators. The titration of spirochetes revealed a dose-independent cytokine response, where 10(3) to 10(7) B. burgdorferi organisms induced similar TNF-like activities but only 10(7) spirochetes induced measurable IL-1-like activities. The release of chemotactic factors was dose dependent and was initiated when tissues were infected with at least 10(5) organisms. We conclude that intact B. burgdorferi or fractions of the bacterium can induce the local up-regulation of TNF-alpha, IL-1alpha, and IL-1beta in the synovium but that the interaction of viable spirochetes with synovial cells leads to the release of IL-8, which probably is a prime initiator of PMN migration during acute Lyme arthritis.
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Grupo Borrelia Burgdorferi/inmunología , Interleucina-1/metabolismo , Interleucina-8/metabolismo , Enfermedad de Lyme/inmunología , Membrana Sinovial/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Anticuerpos Bloqueadores , Grupo Borrelia Burgdorferi/efectos de la radiación , Factores Quimiotácticos/análisis , Quimiotaxis de Leucocito , Recuento de Colonia Microbiana , Medios de Cultivo Condicionados/análisis , Pruebas Inmunológicas de Citotoxicidad , Perros , Técnicas In Vitro , Interleucina-1/análisis , Interleucina-1/genética , Interleucina-8/análisis , Interleucina-8/genética , Neutrófilos/inmunología , Reacción en Cadena de la Polimerasa , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas Recombinantes/inmunología , Sonicación , Membrana Sinovial/metabolismo , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/genética , Rayos Ultravioleta , Regulación hacia ArribaAsunto(s)
Educación Médica , Relaciones Profesional-Paciente , Estudiantes de Medicina , Factores de Edad , Análisis de Varianza , Actitud Frente a la Muerte , Femenino , Homosexualidad , Hostilidad , Humanos , Masculino , Persona de Mediana Edad , Missouri , Simulación de Paciente , Factores SexualesRESUMEN
Twenty 6-week-old specific-pathogen-free beagles were infected with Borrelia burgdorferi by tick challenge, and five uninfected dogs served as controls. During the study, all dogs were monitored for infection, clinical signs, and antibody response against B. burgdorferi. During episodes of lameness or postmortem, synovial fluids from each dog were examined for volume, cell number, polymorphonuclear leukocyte (PMN) content, cell viability, and chemotactic activity. Twenty-five tissues collected postmortem from each dog were tested for interleukin-8 (IL-8) mRNA, tumor necrosis factor alpha (TNF-alpha) mRNA, presence of live spirochetes, and histopathological changes. Thirteen infected dogs (group A), which seroconverted rapidly (maximum titers within 50 to 90 days), developed acute and severe mono- or oligoarthritis almost exclusively in the limb closest to the tick bite (median incubation period, 66 days). Synovial fluids of the arthritic joints collected during episodes of lameness had significantly elevated volume, cell count, PMN proportion, cell viability, and chemotactic activity for PMNs. The remaining joints of the same animals contained synovial fluids with elevated chemotactic activity and cell viability. Twelve dogs tested positive for IL-8 mRNA in multiple tissues (synovia, pericardium, and peritoneum), and 10 dogs expressed TNF-alpha mRNA, but only in the tributary lymph nodes of the inflamed joints. Histological examinations revealed severe poly- or oligoarthritis and moderate to severe cortical hyperplasia in draining lymph nodes of the inflamed joints in all 13 dogs. Seven infected dogs with mild or no clinical signs (group B) seroconverted slowly (peak titers after 90 days), and only some joint fluids showed chemotactic activity, which on average was lower than that in inflamed and noninflamed joints from dogs in group A. Four dogs expressed IL-8 mRNA (in the synovia and pericardium), and three dogs had TNF-alpha mRNA in tributary lymph nodes. Histologically, nonsuppurative arthritis was found in multiple joints, and mild to moderate cortical hyperplasia was found in draining lymph nodes. Five uninfected dogs without lameness (group C) had normal synovial fluids and tissues. In all infected dogs, live spirochetes were demonstrated more frequently in tissues of the somatic quadrant closest to the tick bite than in tissues further from the site of infection, suggesting that dissemination of B. burgdorferi occurs more by migration than by blood-borne spread. From these studies employing a canine model of B. burgdorferi infection, we conclude that IL-8 is involved in the pathogenesis of acute Lyme arthritis.
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Grupo Borrelia Burgdorferi , Interleucina-8/metabolismo , Articulaciones/microbiología , Enfermedad de Lyme/microbiología , Membrana Sinovial/microbiología , Animales , Perros , Articulaciones/patología , Enfermedad de Lyme/metabolismo , Enfermedad de Lyme/patología , Membrana Sinovial/patología , Regulación hacia ArribaRESUMEN
PURPOSE: To determine a set of distinctive imaging findings seen in symptomatic patients with pretibial varices. MATERIALS AND METHODS: Medical records and imaging studies of patients who presented with pretibial varices over an 8-year period were collected from four institutions. Findings in six symptomatic patients with pretibial varices were retrospectively reviewed. Radiographic and magnetic resonance (MR) imaging findings were available from all six patients; findings from several other modalities were also available in some patients. RESULTS: Conventional radiographs showed a small osteolytic defect in the anterior cortex of the midtibia and a prominent, longitudinally oriented, radiolucent groove in the proximal half of the tibial diaphysis. MR images showed pretibial varices connected to an enlarged vessel in the tibia that eventually exited through the nutrient foramen. Computed tomographic (three patients), sonographic (four patients), venographic (four patients), arteriographic (two patients), and surgical (three patients) findings demonstrated that these patients had an unusual intraosseous varix that traversed the anterior cortex, medullary cavity, and posterior cortex of the tibia. CONCLUSION: Recognition of these findings can prevent misdiagnosis and may prove helpful in the planning of appropriate treatment.
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Tibia/irrigación sanguínea , Várices/diagnóstico , Venas/anomalías , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Angiografía por Resonancia Magnética , Masculino , Persona de Mediana Edad , Flebografía , Estudios Retrospectivos , Tibia/diagnóstico por imagen , Tibia/patología , Tomografía Computarizada por Rayos X , Ultrasonografía Doppler Dúplex , Várices/diagnóstico por imagen , Venas/patologíaRESUMEN
Exposure of osteosarcoma cell lines to chronic intermittent strain increases the activity of mechano-sensitive cation (SA-cat) channels. The impact of mechano-transduction on osteoblast function has not been well studied. We analyzed the expression and production of bone matrix proteins in human osteoblast-like osteosarcoma cells, OHS-4, in response to chronic intermittent mechanical strain. The OHS-4 cells exhibit type I collagen production, 1,25-Dihydroxyvitamin D-inducible osteocalcin, and mineralization of the extracellular matrix. The matrix protein message level was determined from total RNA isolated from cells exposed to 1-4 days of chronic intermittent strain. Northern analysis for type I collagen indicated that strain increased collagen message after 48 h. Immunofluorescent labeling of type I collagen demonstrated that secretion was also enhanced with mechanical strain. Osteopontin message levels were increased several-fold by the application of mechanical load in the absence of vitamin D, and the two stimuli together produced an additive effect. Osteocalcin secretion was also increased with cyclic strain. Osteocalcin levels were not detectable in vitamin D-untreated control cells. However, after 4 days of induced load, significant levels of osteocalcin were observed in the medium. With vitamin D present, osteocalcin levels were 4 times higher in the medium of strained cells compared to nonstrained controls. We conclude that mechanical strain of osteoblast-like cells is sufficient to increase the transcription and secretion of matrix proteins via mechano-transduction without hormonal induction.
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Colágeno/biosíntesis , Osteocalcina/biosíntesis , Osteosarcoma/metabolismo , Sialoglicoproteínas/biosíntesis , Northern Blotting , Calcitriol/farmacología , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/metabolismo , Humanos , Osteocalcina/antagonistas & inhibidores , Osteopontina , Osteosarcoma/patología , ARN/análisis , Transducción de Señal , Estrés Mecánico , Células Tumorales CultivadasRESUMEN
The connective tissue-activating peptide III (CTAP-III), which is released from activated platelets, represents an inactive precursor of the chemokine neutrophil-activating peptide 2 (NAP-2). Leukocytes and leukocyte-derived proteases have been found to convert CTAP-III into NAP-2 by proteolytic cleavage at the N terminus. We demonstrate here that rapid and efficient formation of NAP-2 is mediated by neutrophil granulocytes (PMN) but not by monocytes or lymphocytes. However, as seen in a degranulation assay, neutrophils processing CTAP-III did not become activated by the generated NAP-2 and even exhibited decreased responsiveness to high doses of NAP-2 or IL-8, but not to FMLP. The desensitizing effect, being maximal already after 5 min of preincubation with CTAP-III, was not mediated through binding of the precursor to specific receptors but correlated with the rapid down-modulation of common NAP-2/IL-8 high affinity binding sites. A similar functional and receptor desensitization was observed in PMN pre-exposed to nonstimulatory doses of NAP-2. Specific inhibition of the CTAP-III-cleaving enzyme by the serine protease inhibitor aprotinin abrogated the CTAP-III, but not the NAP-2-mediated effects. Desensitization of PMN by CTAP-III was due to NAP-2 generated by proteolytic truncation of CTAP-III. Our results suggest that CTAP-III may regulate PMN activation by protecting processing cells from premature activation.
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Factores de Coagulación Sanguínea/fisiología , Neutrófilos/inmunología , Péptidos/fisiología , Receptores de Citocinas/metabolismo , Factores de Coagulación Sanguínea/metabolismo , Degranulación de la Célula/inmunología , Regulación hacia Abajo/inmunología , Humanos , Interleucina-8/metabolismo , Elastasa de Leucocito , Leucocitos Mononucleares/inmunología , Elastasa Pancreática/sangre , beta-TromboglobulinaRESUMEN
To investigate the coupling between the circadian system and the regulation of the ovarian cycle in nonhuman primates, the effect of Zeitgeber-induced alterations of the circadian period (23 vs 26 h) on the ovarian cycle length was studied in the long-cycling polyestrous common marmoset, Callithrix j. jacchus. For that purpose, six female marmosets were isolated for approximately 4 months each under artificial lighting regimens of 23 h [light-dark (LD) 11.5:11.5] and of 26 h (LD 13:13; 300:0.03 lx). Samples of "morning urine" were collected in each circadian period and analyzed by radioimmunoassay for their estrone (E1) and estradiol-17 beta (E2) concentrations. Clear ovarian cyclic variations of the creatinine related urinary E1 and E2 concentrations were ascertained in each individual, with the E2 concentrations being 5-10 times higher than the E1 concentrations. In a total of 48 recorded ovarian cycles, the cycle length varied between 16 and 39 days and was 28.3 +/- 4.1 days on average. As measured in circadian periods, the marmosets' ovarian cycle was significantly longer (p < 0.05) under entrainment to LD 11.5:11.5 than under entrainment to LD 13:13. When measured in objective days, however, no difference in cycle length was demonstrated. Hence, in Callithrix, the mechanisms regulating the ovarian cycle length do not seem to be closely coupled to the circadian system, but rather corroborate the more classic hypothesis presuming that in polyestrous mammals different (at most weakly coupled) timing mechanisms or oscillator systems are responsible for the regulation of the circadian and the ovarian cycles.
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Callithrix/fisiología , Ritmo Circadiano , Ciclo Menstrual/fisiología , Ovario/fisiología , Animales , Creatinina/orina , Oscuridad , Estradiol/orina , Estrona/orina , Femenino , Luz , Factores de TiempoRESUMEN
Early reports demonstrated the diagnostic advantage of large-core (14-gauge) biopsy over fine-needle aspiration biopsy of nonpalpable lesions of the breast without apparent significant increase in morbidity. A case of malignant seeding of the needle track after a large-core biopsy of a mucinous carcinoma of the breast is documented. The potential for increased risk of tract seeding of malignancy must be considered.
Asunto(s)
Adenocarcinoma Mucinoso/patología , Biopsia con Aguja/efectos adversos , Neoplasias de la Mama/patología , Mama/patología , Siembra Neoplásica , Técnicas Estereotáxicas , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/diagnóstico por imagen , Anciano , Biopsia con Aguja/instrumentación , Biopsia con Aguja/métodos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Humanos , Mamografía , AgujasRESUMEN
Focal abnormal signal intensity within the distal femoral condyles or proximal tibial plateaus is frequently seen on T1- or intermediate-weighted magnetic resonance (MR) images of the knee. To characterize the prevalence and significance of these findings better, a retrospective study of MR imaging of the knee, performed on the first 434 consecutive patients at a primarily outpatient community MR imaging center, was undertaken. A signal intensity loss demonstrated on images with a short echo time (20 or 25 msec) was divided into three types based on morphologic criteria. A type 1 finding was a diffuse, often reticulated signal intensity loss in the metaphyseal and epiphyseal regions of bone. A type 2 loss was associated with an interruption in the smooth, black cortical line. A type 3 finding was a profound signal intensity loss primarily restricted to the immediate subcortical region. Seventeen percent of all cases revealed a type 1 or 2 loss that may have been compatible with acute bone injuries. These bone lesions were frequently associated with tears of the anterior cruciate ligament and contralateral collateral ligament, but infrequently these lesions were detected with plain radiography and arthroscopy. When associated with a weight-bearing cortex, bone injuries detected with MR imaging may explain clinical symptoms of pain on weight bearing, and type 1 injuries may represent regions of bone at increased risk for the subsequent development of insufficiency fractures if the bone is not adequately protected during trabecular healing.