RESUMEN
Disorders of sexual differentiation such as androgen insensitivity and gonadal dysgenesis can involve an intrinsic fluidity at different levels, from the anatomical and biological to the social (gender) that must be considered in the context of social constraints. Sex assignment models based on George Engel's biopsychosocial aspects model of biology accept fluidity of gender as a central concept and therefore help establish expectations within the uncertainty of sex assignment and anticipate potential changes. The biology underlying the fluidity inherent to these disorders should be presented to parents at diagnosis, an approach that the gender medicine field should embrace as good practice. Greek mythology provides many accepted archetypes of change, and the ancient Greek appreciation of metamorphosis can be used as context with these patients. Our goal is to inform expertise and optimal approaches, knowing that this fluidity may eventually necessitate sex reassignment. Physicians should provide sex assignment education based on different components of sexual differentiation, prepare parents for future hormone-triggered changes in their children, and establish a sex-assignment algorithm.
Asunto(s)
Trastornos del Desarrollo Sexual/historia , Trastornos del Desarrollo Sexual/psicología , Identidad de Género , Mitología , Consejo Sexual , Trastornos del Desarrollo Sexual/terapia , Femenino , Antigua Grecia , Historia del Siglo XXI , Historia Antigua , Humanos , Masculino , Mitología/psicología , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Consejo Sexual/métodos , Cirugía de Reasignación de SexoRESUMEN
BACKGROUND AND PURPOSE: Germinal matrix hemorrhage-intraventricular hemorrhage (GMH-IVH) is the most common neurological problem of premature infants and has enormous financial and social impact. Despite this, there is no standardized animal model of IVH depicting acute brain injuries. METHODS: We delivered rabbit-pups prematurely at 29-day gestation by C-section, administered intraperitoneal glycerol to the pups at 3-hour postnatal age to induce IVH, and evaluated the brain for evidence of injuries. RESULTS: About 80% of glycerol-treated pups developed gross IVH. We found greater neutrophil and microglia infiltration around the ventricles (periventricular zone) in pups with IVH than in controls. We noted more apoptosis and neuronal degeneration in the periventricular zone than in the neocortex in pups with IVH, but not in controls. There was evidence of axonal damage revealed by beta-amyloid precursor protein and neurofilament immunolabeling. Neurobehavioral testing showed that pups with IVH were more wobbly with lesser capability to walk on inclination than pups without IVH. There was no evidence of acute systemic toxicity in the glycerol-treated pups. An evaluation of autopsy materials from premature infants revealed similar evidence of apoptosis and cellular infiltration in the periventricular zone in cases with IVH, but not in cases without IVH-suggesting clinical relevance of the model. CONCLUSIONS: The study provides an instructive animal model of IVH with evidence of acute brain injuries that can be used to evaluate strategies in prevention of IVH and acute posthemorrhagic complications.
Asunto(s)
Hemorragia Cerebral/inducido químicamente , Ventrículos Cerebrales/patología , Modelos Animales de Enfermedad , Animales , Animales Recién Nacidos , Apoptosis , Conducta Animal , Encéfalo/patología , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/patología , Hemorragia Cerebral/psicología , Femenino , Edad Gestacional , Glicerol/administración & dosificación , Glicerol/toxicidad , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/patología , Inyecciones Intraperitoneales , Microglía/patología , Degeneración Nerviosa/inducido químicamente , Degeneración Nerviosa/etiología , Neutrófilos/patología , Embarazo , Nacimiento Prematuro , Conejos , Método Simple Ciego , UltrasonografíaRESUMEN
Pelizaeus Merzbacher disease is an X-linked dysmyelinating disorder of the CNS, resulting from mutations in the proteolipid protein (PLP) gene. An animal model for this disorder, the myelin-deficient (MD) rat, carries a point mutation in the PLP gene and exhibits a phenotype similar to the fatal, connatal disease, including extensive dysmyelination, tremors, ataxia, and death at approximately postnatal day 21 (P21). We postulated that early death might result from disruption of myelinated neural pathways in the caudal brainstem and altered ventilatory response to oxygen deprivation or hypercapnic stimulus. Using barometric plethysmography to measure respiratory function, we found that the MD rat develops lethal hypoxic depression of breathing at P21, but hypercapnic ventilatory response is normal. Histologic examination of the caudal brainstem in the MD rat at this age showed extensive dysmyelination and downregulation of NMDA and to a lesser extent GABA(A) receptors on neurons in the nucleus tractus solitarius, hypoglossal nucleus, and dorsal motor nucleus of the vagus. Unexpectedly, immunoreactive PLP/DM20 was detected in neurons in the caudal brainstem. Not all biosynthetic functions and structural elements were altered in these neurons, because phosphorylated and nonphosphorylated neurofilament and choline acetyltransferase expression were comparable between MD and wild-type rats. These findings suggest that PLP is expressed in neurons in the developing brainstem and that PLP gene mutation can selectively disrupt central processing of afferent neural input from peripheral chemoreceptors, leaving the central chemosensory system for hypercapnia intact.