RESUMEN
Alkaptonuria (AKU) is a rare genetic disease resulting in severe, rapidly progressing, early onset multi-joint osteoarthropathy. A potential therapy, nitisinone, is being trialled that reduces the causative agent; homogentisic acid (HGA) and in a murine model has shown to prevent ochronosis. Little is currently known about the effect nitisinone has on osteoarticular cells; these cells suffer most from the presence of HGA and its polymeric derivatives. This led us to investigate nitisinone's effect on chondrocytes and osteoblast-like cells in an in vitro model. Human C20/A4 immortalized chondrocytes, and osteosarcoma cells MG63 cultured in DMEM, as previously described. Confluent cells were then plated into 24-well plates at 4 × 10(4) cells per well in varying concentrations of nitisinone. Cells were cultured for 7 days with medium changes every third day. Trypan blue assay was used to determine viability and the effect of nitisinone concentration on cells. Statistical analysis was performed using analysis of variance, and differences between groups were determined by Newman-Keuls post-test. Analysis of C20/A4 chondrocyte and MG63 osteoblast-like cell viability when cultured in different concentrations of nitisinone demonstrates that there is no statistically significant difference in cell viability compared to control cultures. There is currently no literature surrounding the use of nitisinone in human in vitro models, or its effect on chondrocytes or osteoblast like cells. Our results show that nitisinone does not appear detrimental to cell viability of chondrocytes or osteoblast-like cells, which adds to the evidence that this therapy could be useful in treating AKU.
Asunto(s)
4-Hidroxifenilpiruvato Dioxigenasa/antagonistas & inhibidores , Alcaptonuria/tratamiento farmacológico , Condrocitos/efectos de los fármacos , Ciclohexanonas/uso terapéutico , Nitrobenzoatos/uso terapéutico , Osteoblastos/efectos de los fármacos , Línea Celular Tumoral , Ciclohexanonas/farmacología , Evaluación Preclínica de Medicamentos , Humanos , Nitrobenzoatos/farmacologíaRESUMEN
We examined the escape behavior of larvae and postlarvae of the American lobster (Homarus americanus) and of adult immature (stage ADI) crayfish (Cherax destructor). Responses to standardized water jet stimuli delivered through a pipette were observed and analyzed. Lobster larvae did not respond to stimuli within 60 ms, indicating that they do not have functional giant fibers. The first movement by lobster larvae in response to water jet stimuli was a hyperextension of the abdomen. Larval escape responses also showed very little habituation. Postlarval lobsters and ADI crayfish showed the same range of responses as adult animals. Displacement efficiency of tailflicks exhibited by the different animals and stages was examined and related to the morphology of the animals. A separate behavior from tailflicking by larval lobsters in response to water jet stimuli was also observed. Here, the abdomen was hyperextended and the thoracic appendages were promoted. We termed this behavior a "starburst" response. The features of the tailflicking behavior suggest that it evolved to make the larvae difficult prey to handle for small, slower moving predators, and possibly to allow them to ride the bow waves of faster moving predators.
Asunto(s)
Astacoidea/fisiología , Conducta Animal , Larva/fisiología , Nephropidae/fisiología , Animales , Cola (estructura animal)/química , Cola (estructura animal)/fisiologíaRESUMEN
The BirthPlace program in San Diego, California, is an example of a successfully "mainstreamed" alternative maternity care program. It was developed to address an access to prenatal care problem in the county, and it has successfully integrated four systems of care: 1) a private practice of nurse-midwives and obstetricians, 2) the public community clinic system, 3) the tertiary university hospital, and 4) a freestanding birth center. It provides a model of care that, if replicated, could be an answer for ensuring universal access to maternity care in the United States. The BirthPlace program primarily serves a public-funded, Hispanic population, with certified nurse-midwives as the primary providers. The program's greatest challenge has been to maintain a personalized, family-centered focus, which has been the hallmark of freestanding birth centers to date, in the face of large numbers of clients and low reimbursement for care. The program has addressed the challenge of increasing access and cost-effectiveness while ensuring family-centered care through decentralized clinic management, informed consent, culturally sensitive care, and appropriate use of technology. However, in the face of an ever-changing health care system, balancing these issues will remain a constant challenge as we reshape our maternity care services.