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Statins, which are 3 -hydroxy-3 -methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are widely used for the treatment of hyperlipidemia, and are largely metabolized in the liver. Recent studies and animal data suggest that statins promote osteogenesis and increase bone strength. Physiologically, marked reduction in total cholesterol level may interfere with the synthesis of reproductive and adrenal hormones. However, little is known about the effects of statins delivered by sustained delivery system to a target site of a defect and segmental bone fractures on the morphology of the liver and adrenal gland. Therefore, the purpose of this study was to develop a targeted statin delivery system using Tricalcium Phosphate Lysine (TCPL) for defect and segmental femoral injuries and evaluate the effects on the injured bones and on the histomorphology of the liver and adrenal after sustained delivery of statin for a period of 30 days and 12 weeks post-surgery. At the end of 30 days (Phase I), and 12 weeks (Phase II), all the animals were euthanized (with overdose of halothane). The vital organs (including the liver and adrenal), reproductive organs, and the femoral bones were collected for histomorphological analysis. Simvastatin used in this study significantly increased fracture healing in both phases. However, in Phase I study, the adrenal wet weight recorded in the statin group was slightly higher than the weights recorded for the sham and the control groups, but the difference was not statistically significant (p = 0.157). Also, there was atrophy of the zona fasciculata and the zona reticularis, and compensatory hypertrophy of the medulla of the adrenal glands in the samples taken from two of the rats in Phase I. In addition, the wet weight of the liver in the statin group was not significantly different from the control and the sham groups (p = 0.320), although, there was an insignificant decrease of the wet weight compared to the control and sham groups. The histomorphological evaluation by the Image pro digital analysis showed that the liver morphology was different from the control. There appeared to be an atrophy of the liver, with a denser appearance compared to the control and sham groups (Phase I). In Phase II study, there were no significant morphological and wet weight differences of the liver and adrenal glands in the statin group compared to the control and sham groups. In conclusion, sustained delivery of statin in a short period may lead to alteration of the histomorphology of the liver and adrenal gland in a rat model and with adaptation to normal morphology after a long period of sustained delivery of statin. Keywords: Statins, Fracture, Healing, Drug Delivery System, Tricalcium Phosphate Lysine, Simvastatin, morphological changes, biochemical markers., INTRODUCTION Reproductive hormonal levels may be influenced by the levels or the bioavailability of cholesterol. Estrogen, progesterone, and testosterone are synthesized from a common cholesterol precursor pathway [4]. There is [...]

This study examines socioeconomic conditions, psychosocial stress, and health among 264 infants, children, adolescents, and young adults aged 2 months to 18 years residing in a rural Caribbean village. Fieldwork was conducted over a 9 year period (1988-1996). Research methods and techniques include salivary cortisol radioimmunoassay (N = 22,438), systematic behavioral observations, psychological questionnaires, health evaluations, medical records, informal interviews, and participant observation. Analyses of data indicate complex relations among socioeconomic conditions, stress, and health. Household income, land ownership, parental education, and other socioeconomic measures are weakly associated with child illness. There is no evidence that apparent material benefits of high socioeconomic status - such as improved housing, diet, work loads, and access to private healthcare - have important direct effects on child health in this population. However, social relationships, especially family environment, may have important effects on childhood psychosocial stress and illness. Abnormal glucocorticoid response profiles, diminished immunity, and frequent illness are associated with unstable mating relationships of parents/ caretakers and household composition. We suggest that family relationships and concomitant stresss and immunosuppression are important intermediary links between socioeconomic conditions and child health. Am J Phys Anthropol 102:33-53, 1997. KEY WORDS stress health; family; socioeconomic conditions; Carribean; cortisol; salivary immunoassay

The human neuroendocrine system is highly sensitive to the social environment. Hormones such as testosterone and cortisol are released in response to a wide variety of social stimuli. The evolutionary functions of this sensitivity are not well understood. Longitudinal monitoring of hormones, behavior, and social environment is a promising research paradigm for solving these evolutionary puzzles.

A longitudinal study of stress and women's reproduction in a small Kaqchikel Mayan community in rural Guatemala is reported. The understanding of the effects of stress on the reproductive axis in women is mainly derived from clinical studies of individual stressors.

This study investigated the effects of dual delivery of statin and vancomycin on the healing process of a femoral defect injury using tricalcium phosphate lysine (TCPL) delivery system in an animal model. The experimental design consisted of 14 rats divided into the following three groups: Group I animals (n=5) served as the intact control without treatment. Group II animals (n=5) were subjected to a surgically induced defect (2 mm, midshaft of the right femur) and implanted (IM) with TCPL capsules loaded with vancomycin (20mg) (TCPL-AB). Group III animals (n=4) were operated on in a similar fashion as Group II, and subsequently implanted with TCPL capsules loaded vancomycin (20 mg) plus statin (5 mg). The animals were euthanized at 30 days post-implantation using overdose of isoflourane. The right femurs were then harvested in addition to the vital organs, the reproductive organs, and sample of the adjacent skeletal muscles. The hard and soft tissues were evaluated histopathologically by following laboratory standard techniques. The results of this study indicated that statin plus vancomycin treated animals healed in a greater magnitude than the sham group (independent evaluators (p<0.001)). Histomorphometric analysis demonstrated that exposure to sustained delivery of statin resulted in increased in cortical width compared to the sham and control groups (p<0.05). Furthermore, the periosteal area was significantly greater than the areas observed in sham group (p<0.05). Image analysis revealed that there were more bone formation in the vancomycin and statin exposed animals than the sham. Overall, the use of TCPL system was able to deliver statin in a sustained manner without eliciting any adverse effects on the reproductive, vital organs and the muscles. In conclusion, data obtained from this study demonstrated that sustained delivery of statin resulted in a remarkable increase in osteogenic activity.

Statins, which are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors are widely used for the treatment of hyperlipidemia, and recent studies and animal data suggest that statins promote osteogenesis and increase bone strength. However, little is known about the effects of statins delivered by sustained delivery system to a target site of a defect and segmental bone fractures on certain biochemical markers including reproductive hormones. The purpose of this study was to develop a targeted statin delivery system using Tricalcium Phosphate Lysine (TCPL) for defect and segmental femoral injuries and evaluate the effects on alkaline phosphatase, total protein, malinodialdehyde, glutathione, total cholesterol, testosterone, luteinizing hormone, statins, and follicle-stimulating hormone. Because of the influence oral intake of statins might have on certain body organs, we also examine the histomorphology of the vital and reproductive organs of the animals receiving statins for a period of 30 days and 12 weeks post surgery. Simvastatin used in this study significantly increased fracture healing and without significant influence on the body weights and the weights and morphology of the vital and reproductive organs. There was a significant reduction in the cholesterol levels on the 3rd week in both phases of the study and at the conclusion of the study the difference in the cholesterol levels was no more significant in both phases. Other biochemical markers including plasma LH, FSH and testosterone levels were not affected by active treatment with simvastatin. In conclusion, short and long-term simvastatin treatment delivered at a fracture target site did not influence vital and reproductive organs, the systemic levels of the biochemical markers studied, but was able to effectively stimulate bone formation in simple and complicated segmental fractures.