RESUMEN
Contemporary dental practice requires practitioners who are able to draw upon varying interconnected knowledge and skills, in order to make judgments and take action when faced with multiple, often contradictory, ways of interpreting a situation. However, the curricula that prepare students for dental practice are traditionally based on the theoretical knowledge and technical skills to be gained by students. This is despite evidence in the dental literature of a collective desire for graduates to have more range and depth in their repertoire. Examination of contemporary dental practice through the lens of supercomplexity (Higher Education, 40, 409 and 2000) provides contextual understanding and a platform to explore the types of learning and curriculum approaches that can best prepare students for professional practice. From the insights offered by examples from other professional fields, we, as dental educators, can begin to conceptualise learning dentistry as much more than competency frameworks or descriptions of what students need to know and be able to do. Rather, to equip graduates for contemporary dental practice, the dental curriculum needs to become a vehicle for students to develop personally and professionally as well as teaching the theoretical and technical aspects of dentistry.
Asunto(s)
Competencia Clínica , Educación en Odontología , Curriculum , Estudiantes de OdontologíaRESUMEN
The dental occlusion is an important aspect of clinical dentistry; there are diverse functional demands ranging from highly precise tooth contacts to large crushing forces. Further, there are dogmatic, passionate and often diverging views on the relationship between the dental occlusion and various diseases and disorders including temporomandibular disorders, non-carious cervical lesions and tooth movement. This study provides an overview of the biomechanics of the masticatory system in the context of the dental occlusion's role in function. It explores the adaptation and precision of dental occlusion, its role in bite force, jaw movement, masticatory performance and its influence on the oro-facial musculoskeletal system. Biomechanics helps us better understand the structure and function of biological systems and consequently an understanding of the forces on, and displacements of, the dental occlusion. Biomechanics provides insight into the relationships between the dentition, jaws, temporomandibular joints, and muscles. Direct measurements of tooth contacts and forces are difficult, and biomechanical models have been developed to better understand the relationship between the occlusion and function. Importantly, biomechanical research will provide knowledge to help correct clinical misperceptions and inform better patient care. The masticatory system demonstrates a remarkable ability to adapt to a changing biomechanical environment and changes to the dental occlusion or other components of the musculoskeletal system tend to be well tolerated.
Asunto(s)
Maxilares/fisiología , Maloclusión/fisiopatología , Masticación/fisiología , Músculos Masticadores/fisiología , Movimiento/fisiología , Fenómenos Biomecánicos , Fuerza de la Mordida , HumanosRESUMEN
Self-management (SM) programmes are commonly used for initial treatment of patients with temporomandibular disorders (TMD). The programmes described in the literature, however, vary widely with no consistency in terminology used, components of care or their definitions. The aims of this study were therefore to construct an operationalised definition of self-management appropriate for the treatment of patients with TMD, identify the components of that self-management currently being used and create sufficiently clear and non-overlapping standardised definitions for each of those components. A four-round Delphi process with eleven international experts in the field of TMD was conducted to achieve these aims. In the first round, the participants agreed upon six principal concepts of self-management. In the remaining three rounds, consensus was achieved upon the definition and the six components of self-management. The main components identified and agreed upon by the participants to constitute the core of a SM programme for TMD were as follows: education; jaw exercises; massage; thermal therapy; dietary advice and nutrition; and parafunctional behaviour identification, monitoring and avoidance. This Delphi process has established the principal concepts of self-management, and a standardised definition has been agreed with the following components for use in clinical practice: education; self-exercise; self-massage; thermal therapy; dietary advice and nutrition; and parafunctional behaviour identification, monitoring and avoidance. The consensus-derived concepts, definitions and components of SM offer a starting point for further research to advance the evidence base for, and clinical utility of, TMD SM.
Asunto(s)
Técnica Delphi , Dolor Facial/terapia , Autocuidado , Trastornos de la Articulación Temporomandibular/terapia , Consenso , Terapia por Ejercicio , Dolor Facial/fisiopatología , Humanos , Educación del Paciente como Asunto , Autocuidado/métodos , Trastornos de la Articulación Temporomandibular/fisiopatologíaRESUMEN
Accumulated evidence from experimental animal models suggests that neuroplastic changes at the dorsal horn are critical for the maintenance of various chronic musculoskeletal pain conditions. However, to date, no study has specifically investigated whether neuroplastic changes also occur at this level in humans. Using brain imaging techniques, we sought to determine whether anatomical changes were present in the medullary dorsal horn (spinal trigeminal nucleus caudalis) in subjects with the chronic musculoskeletal pain. In twenty-two subjects with painful temporomandibular disorders (TMDs) and forty pain-free controls voxel based morphometry of T1-weighted anatomical images and diffusion tensor images were used to assess regional grey matter volume and microstructural changes within the brainstem and, in addition, the integrity of ascending pain pathways. Voxel based morphometry revealed significant regional grey matter volume decreases in the medullary dorsal horn, in conjunction with alterations in diffusivity properties, namely an increase in mean diffusivity, in TMD subjects. Volumetric and mean diffusivity changes also occurred in TMD subjects in regions of the descending pain modulation system, including the midbrain periaqueductal grey matter and nucleus raphe magnus. Finally, tractography revealed altered diffusivity properties, namely decreased fractional anisotropy, in the root entry zone of the trigeminal nerve, the spinal trigeminal tract and the ventral trigeminothalamic tracts of TMD subjects. These data reveal that chronic musculoskeletal pain in humans is associated with discrete alterations in the anatomy of the medullary dorsal horn, as well as its afferent and efferent projections. These neural changes may be critical for the maintenance of pathological pain.
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Tronco Encefálico/patología , Sustancia Gris/patología , Imagen por Resonancia Magnética/métodos , Síndrome de la Disfunción de Articulación Temporomandibular/patología , Núcleo Caudal del Trigémino/patología , Adulto , Anciano , Dolor Crónico/patología , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Persona de Mediana Edad , Asta Dorsal de la Médula Espinal/patologíaRESUMEN
The aim was to investigate the effects of isotonic resistance exercise on the electro-myographic (EMG) activity of the jaw muscles during standardised jaw movements. In 12 asymptomatic adults surface EMG activity was recorded from the anterior temporalis and masseter muscles bilaterally and the right anterior digastric muscle during right lateral jaw movements that tracked a target. Participants were randomly assigned to a Control group or an Exercise group. Jaw movement and EMG activity were collected (i) at baseline, before the exercise task (pre-exercise); (ii) immediately after the exercise task (isotonic resistance at 60% MVC against right lateral jaw movements); (iii) after 4 weeks of a home-based exercise programme; and, (iv) at 8-weeks follow-up. There were no significant within-subject or between-group differences in the velocity and amplitude of the right lateral jaw movements either within or between data collection sessions (P > 0.05). However, over the 8 weeks of the study, three of the tested EMG variables (EMG Duration, Time to Peak EMG from EMG Onset, and Time to Peak EMG activity relative to Movement Onset) showed significant (P < 0.05) differences in the five tested muscles. Many of the significant changes occurred in the Control group, while the Exercise group tended to maintain the majority of the tested variables at pre-exercise baseline values. The data suggest a level of variability between recording sessions in the recruitment patterns of some of the muscles of mastication for the production of the same right lateral jaw movement and that isotonic resistance exercise may reduce this variability.
Asunto(s)
Electromiografía , Contracción Isotónica/fisiología , Maxilares/fisiología , Masticación/fisiología , Músculos Masticadores/fisiología , Movimiento/fisiología , Adulto , Ejercicio Físico/fisiología , Femenino , Humanos , MasculinoRESUMEN
There is a need to expand the current temporomandibular disorders' (TMDs) classification to include less common but clinically important disorders. The immediate aim was to develop a consensus-based classification system and associated diagnostic criteria that have clinical and research utility for less common TMDs. The long-term aim was to establish a foundation, vis-à-vis this classification system, that will stimulate data collection, validity testing and further criteria refinement. A working group [members of the International RDC/TMD Consortium Network of the International Association for Dental Research (IADR), members of the Orofacial Pain Special Interest Group (SIG) of the International Association for the Study of Pain (IASP), and members from other professional societies] reviewed disorders for inclusion based on clinical significance, the availability of plausible diagnostic criteria and the ability to operationalise and study the criteria. The disorders were derived from the literature when possible and based on expert opinion as necessary. The expanded TMDs taxonomy was presented for feedback at international meetings. Of 56 disorders considered, 37 were included in the expanded taxonomy and were placed into the following four categories: temporomandibular joint disorders, masticatory muscle disorders, headache disorders and disorders affecting associated structures. Those excluded were extremely uncommon, lacking operationalised diagnostic criteria, not clearly related to TMDs, or not sufficiently distinct from disorders already included within the taxonomy. The expanded TMDs taxonomy offers an integrated approach to clinical diagnosis and provides a framework for further research to operationalise and test the proposed taxonomy and diagnostic criteria.
Asunto(s)
Dolor Facial/etiología , Cefalea/etiología , Trastornos de la Articulación Temporomandibular/clasificación , Trastornos de la Articulación Temporomandibular/diagnóstico , Consenso , Femenino , Humanos , Difusión de la Información , Masculino , Dimensión del Dolor , Guías de Práctica Clínica como Asunto , Rango del Movimiento Articular , Estándares de Referencia , Trastornos de la Articulación Temporomandibular/complicaciones , Trastornos de la Articulación Temporomandibular/fisiopatología , Terminología como AsuntoRESUMEN
Providing dental care for children with neurological special health care needs, including Down syndrome, Cerebral palsy and Autism spectrum disorders, is challenging. They often require repeat exposure to sedation or general anaesthesia for routine dental care. 51 parents of children with special needs completed a questionnaire regarding the acceptance of Silver Fluoride as a treatment option. Background: Silver Diamine Fluoride has become popular as a minimally invasive treatment option for providing oral health care to young or uncooperative children. Silver Fluoride (SF) is a newer development with similar but improved properties. The aim was to determine the acceptance of SDF/SF as treatment option for Children with Special Health Care Needs (CSHCN), including Down Syndrome, Autism Spectrum Disorder and Cerebral Palsy. Methods: 51 Parents of CSHCN completed a questionnaire on the overall acceptance of SF; aesthetic concerns related to the location of application; the use of SDF as an alternative to general anesthesia; and the composition of SF. Results: The use of SF on posterior teeth were more acceptable (70.59%) as opposed to its application to anterior teeth (50.98%). Parents generally agreed/ strongly agreed to the use of SF to reduce infection and pain (82%); to avoid treatment under GA (26.70%); and to avoid an injection (78%). 64% of parents indicated their agreement in using SF because it has a reduced cost when compared to a conventional restoration. Majority of parents were in agreement to use SF even if it contains Fluoride (84%) and Silver (78%). Conclusion: The use of SF, as treatment option for caries, was well accepted by South African parents of CSHCN. Shared decision making should be applied when considering SF as treatment option for CSHCN.
RESUMEN
Masticatory efficiency in individuals with extensive tooth loss has been widely discussed. However, little is known about jaw movement smoothness during chewing and the effect of differences in food bolus location on movement smoothness and masticatory efficiency. The aim of this study was to determine whether experimental differences in food bolus location (anterior versus posterior) had an effect on masticatory efficiency and jaw movement smoothness. Jaw movement smoothness was evaluated by measuring jerk-cost (calculated from acceleration) with an accelerometer that was attached to the skin of the mentum of 10 asymptomatic subjects, and acceleration was recorded during chewing on two-colour chewing gum, which was used to assessed masticatory efficiency. Chewing was performed under two conditions: posterior chewing (chewing on molars and premolars only) and anterior chewing (chewing on canine and first premolar teeth only). Jerk-cost and masticatory efficiency (calculated as the ratio of unmixed azure colour to the total area of gum, the unmixed fraction) were compared between anterior and posterior chewing with the Wilcoxon signed rank test (two-tailed). Subjects chewed significantly less efficiently during anterior chewing than during posterior chewing (P = 0·0051). There was no significant difference in jerk-cost between anterior and posterior conditions in the opening phase (P = 0·25), or closing phase (P = 0·42). This is the first characterisation of the effect of food bolus location on jaw movement smoothness at the same time as recording masticatory efficiency. The data suggest that anterior chewing decreases masticatory efficiency, but does not influence jerk-cost.
Asunto(s)
Maxilares/fisiología , Masticación/fisiología , Movimiento/fisiología , Adulto , Goma de Mascar , Femenino , Humanos , Masculino , Proyectos Piloto , Adulto JovenRESUMEN
Peripheral nerve injuries with substantial tissue loss require autologous nerve transplantation or alternatively reconstruction with nerve conduits. Axonal elongation after nerve transection is about 1 mm/day. The precise time course of axonal regeneration on an ultrastructural level in nerve gap repair using either autologous or artificial implants has not been described. As peripheral nerve regeneration is a highly time critical process due to deterioration of the neuromuscular junction, this in vivo examination in a large animal model was performed in order to investigate axonal elongation rates and spider silk material degradation in a narrowly delimited time series (20, 30, 40, 50, 90, 120, 150 and 180 days) by using a novel spider silk based artificial nerve graft as a critical prerequisite for clinical translation. Autologous nerves or artificial nerve conduits based on spider silk of the spider species Trichonephila edulis were transplanted in a 6.0 cm nerve defect model in the black headed mutton. At each of the post-implant time point, electrophysiology recordings were performed to assess functional reinnervation of axonal fibers into the implants. Samples were analyzed by histology and immunofluorescence in order to verify the timeline of axonal regeneration including axonal regeneration rates of the spider silk implant and the autologous transplant groups. Spider silk was degraded within 3 month by a light immune response mainly mediated by Langhans Giant cells. In conjunction with behavioral analysis and electrophysiological measurements, the results indicate that the spider silk nerve implant supported an axonal regeneration comparable to an autologous nerve graft which is the current gold standard in nerve repair surgery. These findings indicate that a biomaterial based spider silk nerve conduit is as effective as autologous nerve implants and may be an important approach for long nerve defects.
Asunto(s)
Tejido Nervioso , Traumatismos de los Nervios Periféricos , Animales , Regeneración Nerviosa , Células de Schwann , Nervio Ciático , Ovinos , SedaRESUMEN
BACKGROUND: The "gate control" theory suggests pain can be reduced by simultaneous activation of nerve fibres that conduct non-noxious stimuli. This study investigated the effects of vibration stimuli on pain experienced during local anaesthetic injections. METHODS: In a preliminary study, subjects were asked to rate anticipated and actual pain from regional anaesthetic injections in the oral cavity. A second study compared, within subjects, pain from injections with and without a simultaneous vibration stimulus. Both infiltration and block anaesthetic injection techniques were assessed. In each subject, two similar injections were given and with one, a vibration stimulus was randomly allocated. Injection pain was assessed by visual analogue scale and McGill pain descriptors. RESULTS: Both infiltration and block injections were painful (mean anticipated intensity: 31.25, actual: 17.82 mm on 100 mm scale). Pain intensity with and without vibration was 12.9 mm (range 0-67) and 22.2 mm (range 0-83) respectively (p = 0.00005, paired T-test), and this effect was seen with both infiltration (p = 0.032) and block anaesthetic (p = 0.0001) injection subgroups. Furthermore, compared to no vibration-stimulus injections, injections with vibration resulted in less pain descriptors chosen (p = 0.004), and the descriptors had a lower pain rating (p = 0.001). CONCLUSIONS: The results suggest that vibration can be used to decrease pain during dental local anaesthetic administration.
Asunto(s)
Anestesia Dental/métodos , Anestésicos Locales/administración & dosificación , Dolor/prevención & control , Enmascaramiento Perceptual , Vibración , Adolescente , Adulto , Anciano , Anestesia Local/métodos , Femenino , Humanos , Inyecciones/efectos adversos , Masculino , Nervio Mandibular/efectos de los fármacos , Persona de Mediana Edad , Bloqueo Nervioso/métodos , Dolor/etiología , Dimensión del Dolor , Resultado del Tratamiento , Adulto JovenRESUMEN
In developing muscle, synapse elimination reduces the number of motor axons that innervate each postsynaptic cell. This loss of connections is thought to be a consequence of axon branch trimming. However, branch retraction has not been observed directly, and many questions remain, such as: do all motor axons retract branches, are eliminated branches withdrawn synchronously, and are withdrawing branches localized to particular regions? To address these questions, we used transgenic mice that express fluorescent proteins in small subsets of motor axons, providing a unique opportunity to reconstruct complete axonal arbors and identify all the postsynaptic targets. We found that, during early postnatal development, each motor axon loses terminal branches, but retracting branches withdraw asynchronously and without obvious spatial bias, suggesting that local interactions at each neuromuscular junction regulate synapse elimination.
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Proteínas Luminiscentes/genética , Neuronas Motoras/fisiología , Músculo Esquelético/inervación , Unión Neuromuscular/fisiología , Sinapsis/fisiología , Envejecimiento , Animales , Animales Recién Nacidos , Axones/fisiología , Proteínas Bacterianas/análisis , Proteínas Bacterianas/genética , Proteínas Fluorescentes Verdes , Proteínas Luminiscentes/análisis , Ratones , Ratones Transgénicos , Modelos Neurológicos , Unión Neuromuscular/ultraestructura , Sinapsis/ultraestructuraRESUMEN
We generated transgenic mice in which red, green, yellow, or cyan fluorescent proteins (together termed XFPs) were selectively expressed in neurons. All four XFPs labeled neurons in their entirety, including axons, nerve terminals, dendrites, and dendritic spines. Remarkably, each of 25 independently generated transgenic lines expressed XFP in a unique pattern, even though all incorporated identical regulatory elements (from the thyl gene). For example, all retinal ganglion cells or many cortical neurons were XFP positive in some lines, whereas only a few ganglion cells or only layer 5 cortical pyramids were labeled in others. In some lines, intense labeling of small neuronal subsets provided a Golgi-like vital stain. In double transgenic mice expressing two different XFPs, it was possible to differentially label 3 neuronal subsets in a single animal.
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Proteínas Luminiscentes/biosíntesis , Microscopía Fluorescente/métodos , Neuronas/metabolismo , Neuronas/ultraestructura , Animales , Axones/metabolismo , Axones/ultraestructura , Linaje de la Célula , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Color , Dendritas/metabolismo , Dendritas/ultraestructura , Proteínas Fluorescentes Verdes , Luz , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/toxicidad , Ratones , Ratones Transgénicos , Unión Neuromuscular/metabolismo , Unión Neuromuscular/ultraestructura , Neuronas/clasificación , Terminales Presinápticos/metabolismo , Terminales Presinápticos/ultraestructura , Secuencias Reguladoras de Ácidos Nucleicos/genética , Células Ganglionares de la Retina/citología , Células Ganglionares de la Retina/metabolismo , Sinapsis/metabolismo , Sinapsis/ultraestructura , Antígenos Thy-1/genética , TransgenesRESUMEN
Pain and limitation of movement are two cardinal symptoms of temporomandibular disorders but it is unclear how one influences the other. The relationship between pain and movement is clinically significant but controversial with two major theories having been proposed: the Vicious Cycle Theory and the Pain Adaptation Model. The Vicious Cycle Theory proposes a vicious cycle between pain and muscle activity. This theory has little scientific basis but underpins many management strategies. The Pain Adaptation Model is more evidence-based and proposes that pain causes changes in muscle activity to limit movement and protect the sensory-motor system from further injury. The Pain Adaptation Model has many positive features but does not appear to explain the relation between pain and muscle activity in all situations. We propose that the relationship is influenced by the functional complexity of the sensory-motor system and the multidimensional nature of pain. This new Integrated Pain Adaptation Model states that pain results in a new recruitment strategy of motor units that is influenced by the multidimensional (i.e., biological and psychosocial) components of the pain experience. This new recruitment strategy aims to minimize pain and maintain homeostasis. This model emphasizes the individual reaction to pain and suggests a tailored approach towards management.
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Dolor Facial/fisiopatología , Músculo Masetero/fisiología , Actividad Motora/fisiología , Adaptación Fisiológica , Animales , Músculos Faciales/fisiología , Humanos , Modelos Biológicos , Reclutamiento Neurofisiológico , Trastornos de la Articulación Temporomandibular/fisiopatologíaRESUMEN
The neural mechanisms underlying the development and maintenance of chronic pain following nerve injury remain unclear. There is growing evidence that chronic neuropathic pain is associated with altered thalamic firing patterns, thalamocortical dysrhythmia and altered infra-slow oscillations in ascending pain pathways. Preclinical and post-mortem human studies have revealed that neuropathic pain is associated with prolonged astrocyte activation in the dorsal horn and we have suggested that this may result in altered gliotransmission, which results in altered resting neural rhythm in the ascending pain pathway. Evidence of astrocyte activation above the level of the dorsal horn in living humans is lacking and direct measurement of astrocyte activation in living humans is not possible, however, there is evidence that regional alterations in T2 relaxation times are indicative of astrogliosis. The aim of this study was to use T2 relaxometry to explore regional brain anatomy of the ascending pain pathway in individuals with chronic orofacial neuropathic pain. We found that in individuals with trigeminal neuropathic pain, decreases in T2 relaxation times occurred in the region of the spinal trigeminal nucleus and primary somatosensory cortex, as well as in higher order processing regions such as the dorsolateral prefrontal, cingulate and hippocampal/parahippocampal cortices. We speculate that these regional changes in T2 relaxation times reflect prolonged astrocyte activation, which results in altered brain rhythm and ultimately the constant perception of pain. Blocking prolonged astrocyte activation may be effective in preventing and even reversing the development of chronic pain following neural injury.
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Encéfalo/fisiopatología , Dolor Crónico/fisiopatología , Neuralgia/fisiopatología , Relajación/fisiología , Adulto , Encéfalo/metabolismo , Dolor Crónico/metabolismo , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Dimensión del Dolor/métodosRESUMEN
It has been proposed that pain competes with other attention-demanding stimuli for cognitive resources, and many chronic pain patients display significant attention and mental flexibility deficits. These alterations may result from disruptions in the functioning of the default mode network (DMN) which plays a critical role in attention, memory, prospection and self-processing, and recent investigations have found alterations in DMN function in multiple chronic pain conditions. Whilst it has been proposed that these DMN alterations are a characteristic of pain that is chronic in nature, we recently reported altered oscillatory activity in the DMN during an acute, 5 minute noxious stimulus in healthy control subjects. We therefore hypothesize that altered DMN activity patterns will not be restricted to those in chronic pain but instead will also occur in healthy individuals during tonic noxious stimuli. We used functional magnetic resonance imaging to measure resting state infra-slow oscillatory activity and functional connectivity in patients with chronic orofacial pain at rest and in healthy controls during a 20-minute tonic pain stimulus. We found decreases in oscillatory activity in key regions of the DMN in patients with chronic pain, as well as in healthy controls during tonic pain in addition to changes in functional connectivity between the posterior cingulate cortex and areas of the DMN in both groups. The results show that similar alterations in DMN function occur in healthy individuals during acute noxious stimuli as well as in individuals with chronic pain. These DMN changes may reflect the presence of pain per se and may underlie alterations in attentional processes that occur in the presence of pain.
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Dolor Agudo/fisiopatología , Encéfalo/fisiopatología , Dolor Crónico/fisiopatología , Dolor Agudo/diagnóstico por imagen , Adulto , Atención/fisiología , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Dolor Crónico/diagnóstico por imagen , Dolor Facial/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatologíaRESUMEN
Resistance to infection with the multicellular parasite Schistosoma mansoni has been previously demonstrated to vary among several host species. The current investigation was designed to examine the basis for this species-related resistance in vitro. Adherent peritoneal macrophages or peripheral blood mononuclear cells from several species of host animals were incubated with S. mansoni schistosomula for 18-24 h; parasite viability was then assayed by methylene blue exclusion. Peritoneal exudate macrophages from susceptible species, such as mice (C57Bl/6) and hamsters killed, respectively, 6.6 +/- 2 and 8.0 +/- 2% of incubated schistosomula. In contrast, cells from resistant species: rats, guinea pigs, and rabbits, killed 21 +/- 2.3, 15 +/- 4.6, and 17 +/- 5.5%, respectively. Furthermore, blood monocytes from rabbits resulted in a mean of 25.9 +/- 2.8% dead organisms. Schistosomula killing by mononuclear phagocytes obtained from resistant species (rats or rabbits) was dependent on the cell/parasite ratio. Significant schistosomula mortality resulted from culture supernatants of rat macrophages or rabbit monocytes. Killing by cells from both species was significantly reduced upon addition of L-arginine, while catalase reduced killing only by rat macrophages. We conclude that mononuclear phagocytes may play a key role in species-related innate resistance to schistosomiasis; their in vitro schistosomulicidal activity parallels the known in vivo susceptibility of the donor species. Killing is mediated by lysosomal enzymes (arginase) and by products of oxidative metabolism, the predominant mechanism depends on the specific animal species.
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Fagocitos/inmunología , Esquistosomiasis/inmunología , Animales , Líquido Ascítico/citología , Células Cultivadas , Inmunidad Innata , Macrófagos/inmunología , Ratones , Schistosoma mansoniRESUMEN
Transforming growth factor-beta (TGF beta) promotes deposition of extracellular matrix and is associated with fibrotic conditions both in experimental animals and in humans. Although a role for mast cells has been suspected in the pathogenesis of fibrosis, no potent mediator capable of stimulating fibroblast growth or extracellular matrix deposition has been identified in mast cell supernatants. We report here the constitutive production of TGF beta 1 by four dog mastocytoma cell lines. TGF beta 1 was identified by characteristic biologic activity, blockade of biologic effect by specific neutralizing antibody, and by recognition of a band with the appropriate migration by western blot. TGF beta 1 mRNA, but not TGF beta 2 or TGF beta 3 mRNA, was also produced constitutively by all four cell lines. Quantitation by bioassay revealed baseline TGF beta secretion of approximately 1 ng/10(6) cells over 48 h. Stimulation of mastocytoma cells with phorbol ester increased the rate of release of TGF beta 1, most markedly in the first 30 min after stimulation, without increasing TGF beta 1 mRNA. Dog mastocytoma cells produced TGF beta 1 primarily in a latent form, inactive until treated with acid. Both pure TGF beta 1 and TGF beta-containing mastocytoma cell-conditioned media inhibited mitogenesis and proliferation in dog mastocytoma cell lines, suggesting that mast cell tumor lines would not grow preferentially based on their ability to produce TGF beta. These studies may make possible further investigation of the mechanism by which mast cells contribute to the induction of fibrosis.
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Sarcoma de Mastocitos/metabolismo , Factor de Crecimiento Transformador beta/biosíntesis , Animales , División Celular , Perros , Sarcoma de Mastocitos/patología , ARN Mensajero/análisis , Acetato de Tetradecanoilforbol/farmacología , Factor de Crecimiento Transformador beta/genética , Células Tumorales CultivadasRESUMEN
Recent market withdrawals of prescription drug products have brought attention to premarketing safety research. Less known but related to some drug withdrawals are postmarketing dosage changes of newly marketed drugs, including both dosage reductions and increases. These events have serious effects on patients, manufacturers, and regulatory authorities. Most of these harmful events could be avoided by intensive employment of targeted clinical pharmacology investigations to optimize dosage prior to phase III testing and regulatory approval. In this paper, the frequency and implications of postmarketing dosing changes and market withdrawals are considered in light of approaches to preventing them.