The relationship between particle morphology and rheological properties in injectable nano-hydroxyapatite bone graft substitutes.

Biomaterials composed of hydroxyapatite (HA) are currently used for the treatment of bone defects resulting from trauma or surgery. However, hydroxyapatite supplied in the form of a paste is considered a very convenient medical device compared to the materials where HA powder and liquid need to be mixed immediately prior to the bone treatment during surgery. In this study we have tested a series of hydroxyapatite (HA) pastes with varying microstructure and different rheological behaviour to evaluate their injectability and biocompatibility. The particle morphology and chemical composition were evaluated using HRTEM, XRD and FTIR. Two paste-types were compared, with the HA particles of both types being rod shaped with a range of sizes between 20 and 80nm while differing in the particle aspect ratio and the degree of roundness or sharpness. The pastes were composed of pure HA phase with low crystallinity. The rheological properties were evaluated and it was determined that the pastes behaved as shear-thinning, non-Newtonian liquids. The difference in viscosity and yield stress between the two pastes was investigated. Surprisingly, mixing of these pastes at different ratios did not alter viscosity in a linear manner, providing an opportunity to produce a specific viscosity by mixing the two materials with different characteristics. Biocompatibility studies suggested that there was no difference in vitro cell response to either paste for primary osteoblasts, bone marrow mesenchymal stromal cells, osteoblast-like cells, and fibroblast-like cells. This class of nanostructured biomaterial has significant potential for use as an injectable bone graft substitute where the properties may be tailored for different clinical indications.

Endogenous oestradiol regulates progesterone receptor expression in the brain of female rat fetuses: what is the source of oestradiol?

Testosterone secreted by male testes during fetal development is aromatized to oestradiol (E(2)) or reduced to the androgen, dihydrotestosteorne (DHT), within specific tissues. The female brain is assumed to develop in the relative absence of gonadal steroid hormones, as the ovary is steroidogenically quiescent until later in postnatal life. However, the proximity of a female fetus to male littermates in utero can increase her exposure to testosterone, and thereby its metabolites. To date, it is has been difficult to dissociate the effects of male-derived E(2) from those of DHT on the developing female brain. In the present study, anogential distance (AGD) in females was used as an androgen-dependent bioassay, whereas progesterone receptor (PR) expression within the medial preoptic nucleus (MPN) was used as an E-dependent measure. Pregnant dams received the aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), or vehicle from embryonic day 16 (ED16) to ED21. On ED22, AGD and PR-immunoreactivity (-ir) were measured in females that had zero, one, or two males (0-2M) or females that had three, four, or five males (3-5M) in the uterine horn. AGD was significantly greater in 3-5M females compared to 0-2M females, suggesting that male littermates are the source of androgenic exposure in the female fetus. ATD treatment significantly decreased PR-ir in the MPN, demonstrating E(2) regulation of PR. However, the total number of males in the uterine horn did not effect PR expression. There was no correlation between PR-ir and AGD, suggesting that these measures are influenced independently. Together, these results suggest that although male littermates provide a significant source of androgens to female fetuses, the amount of E(2) aromatized from male-derived testosterone may not be the only biologically relevant source of androgens or E(2). Alternative sources of E(2) may be essential in ensuring the normal development of the female brain.

Evolución del hemitiroides residual tras hemitiroidectomía por nódulo único / Follow-up of remnant thyroid tissue after hemithyroidectomy for solitary nodules

La evolución del hemitiroides residual y la recidiva del bocio tras la realización de una hemitiroidectomía por bocio nodular único es un aspecto controvertido y no resuelto. Con el fin de intentar analizar el problema se ha realizado una revisión bibliográfica, y se aportan los resultados preliminares de 2 estudios prospectivos a largo plazo sobre la evolución de la hiperplasia del lóbulo residual y el efecto del tratamiento supresor con tiroxina. Tras una hemitiroidectomía por bocio nodular único, folicular o coloide, sin datos de sospecha de enfermedad autoinmunitaria, el 47,7% de los pacientes presentan signos ecográficos de hiperplasia, generalmente micronodular. Las formas macronodulares presentan una mayor tendencia a la progresión, que ocurre en el 72,7% de los casos y es dependiente del tipo de bocio operado, pues en los casos de adenoma folicular se observa progresión en el 17,6% y en los nódulos coloide en el 57,1% de los casos. El 54% de los pacientes operados requieren tratamiento con hormona tiroidea, en el 27,7% por hipotiroidismo subclínico, que es más frecuente tras cirugía por nódulo coloide (45,8%) que por adenoma folicular (17%). El tratamiento supresor con hormona tiroidea realizado a partir de los 6 meses del diagnóstico de la hiperplasia controla la evolución en el 86% de los casos operados por adenoma folicular frente a tan sólo el 38,5% de los operados por nódulos coloides; su utilización debe valorarse de acuerdo con el criterio riesgo/beneficio especialmente en pacientes mayores de 60 años. Por todo ello, la hemitiroidectomía por nódulo único debe diseñarse de acuerdo con una correcta valoración preoperatoria de los datos clínicos, hormonales, ecográficos y citológicos, y no debe plantearse en todos los casos como una intervención estándar; en las revisiones clínicas debe incluirse siempre, además de los estudios hormonales, una ecografía con determinación de volumen del hemitiroides residual (AU)

The follow-up of residual thyroid tissue and goiter recurrence after hemithyroidectomy for solitary nodular goiter is a controversial issue that has not been resolved. To analyze the problem, we performed a literature review. The preliminary results of two long-term prospective studies on the evolution of hyperplasia of the residual lobe and the effect of thyroxine suppression therapy are reported. After hemithyroidectomy for solitary nodular goiter, whether follicular or colloid, 47.7% of patients without suspected autoimmune disease show ultrasonographic signs of hyperplasia, usually micronodular. These forms have a greater tendency to progress, which occurs in 72.7%. Progression depends on the type of goiter resected since it occurs in 17.6% of follicular adenomas and in 57.1% of colloid nodules. Fifty-four percent of patients who undergo surgery require thyroid hormone treatment. This therapy is required for subclinical hypothyroidism in 27.7%, which is more frequent after surgery for colloid nodules (45.8%) than follicular adenomas (17%). Thyroid hormone suppression therapy starting 6 months after diagnosis of hyperplasia controls progression in 86% of patients who undergo surgery for follicular adenoma compared with only 38.5% of those who undergo surgery for colloid nodules. The risk/benefit ratio of this therapy should be evaluated, especially in patients aged more than 60 years. In view of the above, hemithyroidectomy for solitary nodules should be performed after careful preoperative evaluation of clinical, hormonal, ultrasonographic and cytological data. It should not be performed in all patients as a standard procedure and, in addition to hormone studies, follow-up should always include ultrasonography with determination of residual thyroid volume (AU)

Regulation of sex differences in progesterone receptor expression in the medial preoptic nucleus of postnatal rats.

The medial preoptic nucleus (MPN) of the rat, an excellent model for understanding the mechanisms involved in sexual differentiation, is highly sensitive to gonadal hormones during both pre- and post-natal life. Progesterone receptor (PR) expression is sexually dimorphic in the prenatal MPN. Males have significantly higher levels of PR-immunoreactivity (PRir) than females from approximately embryonic day 19 through at least the day of birth, suggesting that PR may play a role in sexual differentiation. Because the MPN is still sensitive to steroid hormones postnatally, the present study investigated PR expression in the MPN of males and females after birth using immunocytochemistry. Results indicate that a sex difference in PR expression persists until at least postnatal day (P) 28. However, females begin to express PR around P10. Because oestradiol regulates PR expression in the adult brain, this study also examined the influence of gonadal hormones on PR expression in the neonatal male and female MPN. Castration on the day of birth significantly reduced levels of PRir in the MPN by 24 h following surgery. Ovariectomy on P4, before the onset of ovarian steroidogenesis, prevented the induction of PR expression in the female MPN, observed in controls by P13. In both sexes, the presence of PRir in the MPN is dependent on gonadal hormone exposure. These findings suggest that differences in steroid secretion by the neonatal male and female gonads are responsible for producing sex differences in the level of PR expression in the postnatal MPN.

Effects of neonatal RU486 on adult sexual, parental, and fearful behaviors in rats.

Exposure to gonadal hormones during perinatal life influences later behavior. The finding that sex differences exist in progestin receptor expression in the perinatal rat brain suggests differential sensitivity of male and female brains to progesterone (C. K. Wagner, A. N. Nakayama, & G. J. De Vries, 1998). Because these sex differences are in neural sites that influence sexually differentiated sexual, parental, and fearful behaviors in adults, this study examined the effects of administering the progestin receptor antagonist RU486 for the first 10 days after birth on these behaviors in adulthood. Neonatal RU486 significantly reduced sexual behavior in males but did not impair reproduction in females. Neonatal RU486 did not affect parental responses of virgin rats exposed to pups (sensitization) but reduced fear in the elevated plus-maze in both sexes. Treatment of pups with RU486 affected neither mother-litter interactions nor plasma testosterone levels in males during or after treatment. These results suggest that neonatal exposure to progesterone, in addition to androgens and estrogens, influences behavioral development in rats.

Activity-stress increases density of GFAP-immunoreactive astrocytes in the rat hippocampus.

Although past research has indicated that stress and the accompanying increase in glucocorticoids compromises hippocampal neurons, little is known about the effect of stress on hippocampal glial cells. In the current study, male rats were exposed to activity-stress (A-S) for six days; this comprised housing with an activity wheel and restricted access (1h/day) to food. Physiological data (e.g., relative adrenal and thymus weights, gastric ulceration) suggested that the A-S rats experienced more stress than pair-fed (no wheel) and control (fed ad libitum, no wheel) rats. Whereas stress did not influence the quantitative morphology of glial fibrillary acidic protein (GFAP)-immunoreactive cells, a semi-quantitative analysis revealed that the A-S rats had significantly more (30%) GFAP-immunoreactive cells in the hippocampal CA3 region than the control rats. Based on the present findings, it appears that the hippocampal astrocytic response to chronic stress may be similar to the response found in endangered, or challenged hippocampal environments, such as in ischemia.