The effect of T-2 toxin on bone microstructure in rabbits

T-2 toxin is the most toxic of the trichothecene mycotoxins. Its effect on bone microstructure is still unknown. This study focuses on acute effects of the T-2 toxin on compact and trabecular bone tissues structure of rabbits after a single intramuscular administration. Experimental E group (n?=?4) consisted of animals which were intramuscularly injected with T-2 toxin at dose 0.08 mg.kg^?1 body weight 72 h before slaughter. Group C (n?=?4) without T-2 toxin application served as a control. An absence of primary vascular longitudinal bone tissue near endosteal surfaces, its deposition on periosteal surfaces and a lower density of secondary osteons in the middle part of the substantia compacta were observed in both females and males injected with T-2 toxin. On the contrary, morphometrical analysis of the compact bone showed no demonstrable alternations in the sizes of primary osteons’ vascular canals, Haversian canals or secondary osteons between rabbits from E and C groups. Also, no significant effects of the T-2 toxin on trabecular bone morphometry and cortical bone thickness were observed between rabbits of either sex. The single intramuscular application of T-2 toxin at the dose used in our study affects only qualitative histological characteristics of the compact bone in rabbits.     

Patterns of femoral bone remodeling dynamics in a medieval Nubian population

The relationship between age, sex and histomorphometry in femoral cortical bone was examined in a skeletal population of late Medieval antiquity (AD 1250–1450) from Kulubnarti, in Sudanese Nubia. These skeletal remains are naturally mummified and in an excellent state of preservation. The study sample consisted of femoral cross sections from 24 females and 19 males ranging in age from 20 to 50+ years. Femoral cross sections were examined using an image analysis system. Numbers of secondary osteons and osteon fragments were counted, osteon area and Haversian canal area were measured, and several variables were calculated to assess differences between sexes and among age groups in bone remodeling variables. The results indicate significant differences between the sexes in osteon number and size. Males had significantly more intact osteons than females, whereas females had significantly larger osteons than males. Haversian canal dimensions were not statistically significant between the sexes. Sex differences in activity patterns in which males were involved in more physically strenuous tasks may have contributed to differences in remodeling variables. Interpopulational comparisons suggest that mechanical strain affects the microstructural features examined in this study. In particular, small Haversian canals in some archaeological skeletal populations are associated with higher bone volume, which may result from high levels of mechanical strain. Am J Phys Anthropol 104:133–146, 1997. © 1997 Wiley-Liss, Inc.     

Simultaneous subchronic exposure to selenium and diazinon as possible risk factor for osteoporosis in adult male rats

Background

Osteoporosis and its main health outcome, fragility fractures, are large and escalating health problems. Skeletal damage may be the critical result of low-level prolonged exposure to several xenobiotics in the general population, but the mechanisms of their adverse effects are not clearly understood. The current study was aimed to investigate the possible ability of simultaneous subchronic peroral administration of selenium (Se) and diazinon (DZN) to induce changes in bone of adult male rats.In our study, twenty 1-month-old male Wistar rats were randomly divided into two experimental groups. In the first group, young males were exposed to 5 mg Na₂SeO₃/L and 40 mg of DZN/L in drinking water, for 90 days. Ten 1-month-old males without Se and DZN intoxication served as a control group. At the end of the experiment, macroscopic and microscopic structures of the femurs were analysed using analytical scales, sliding instrument, and polarized light microscopy.

Results

The body weight, femoral length and cortical bone thickness were significantly decreased in rats simultaneously exposed to Se and DZN (P?<?0.05). These rats also displayed different microstructure in the middle part of the compact bone where vascular canals expanded into central area of substantia compacta. The canals occurred only near endosteal surfaces in rats from the control group. Additionally, a smaller number of primary and secondary osteons, as well as a few resorption lacunae were observed near endosteal surfaces in rats simultaneously administered to Se and DZN. The resorption lacunae as typical structures of bone resorption manifestation are connected with an early stage of osteoporosis. Histomorphometric analysis revealed that area, perimeter, maximum and minimum diameters of primary osteons’ vascular canals were significantly increased (P?<?0.05) in the Se-DZN-exposed rats. On the other hand, all measured variables of Haversian canals and secondary osteons were considerable reduced (P?<?0.05) in these rats.

Conclusions

Simultaneous subchronic peroral exposure to Se and DZN induces changes in macroscopic and microscopic structures of the femurs in adult male rats, and also it can be considered as possible risk factor for osteoporosis. The current study contributes to the knowledge on damaging impact of several xenobiotics on the bone.

     

Quantitative histology of changes with age in rat bone cortex

Changes with age in bone cortex of the rat were investigated by establishing histological parameters which could be quantitated to estimate age at death. Decalcified cross sections of mandible, femur and tibia were prepared from rats two to 120 days old, and measurements were made of: (1) number of osteons, (2) average number of lamellae per osteon, (3) average Haversian canal diameter, and (4) number of non-Haversian (primary) canals. Multiple regression techniques were used to estimate age at death from several combinations of these variables. With age, the number of osteons per unit area of bone and the number of lamellae per osteon increased, but Haversian canal diameter and the number of primary canals decreased. Multiple regression analyses indicated that age at death could be estimated to ± 3 days of the true value in 95% of the cases. Nomographs based on histological measurements of each bone were prepared which can provide accurate estimates of age between two and 120 days in the Sprague-Dawley female rat. It was concluded that microstructure of bone cortex can not only be quantitated to provide accurate estimates of age but it may also constitute a sensitive measure of the metabolic state of the organism. The techniques utilized should prove useful in anthropology as well in studies of bone aging.     

Acute and subchronic co-administrations to cadmium,diazinon and selenium induce apparent osteoporotic symptoms in adult male rats

Cadmium (Cd) and diazinon (DZN) are known to be environmental risk factors for various bone diseases including osteoporosis. Selenium (Se), an essential constituent of many antioxidant enzymes, has in higher concentrations negative effects on the bone. The present study was aimed to investigate possible changes in femoral bone of adult male rats after their acute and subchronic exposures to Cd, DZN and Se. A total of 30 male Wistar rats were randomized into three experimental groups. The rats in the group A (4-months-old) were injected intraperitoneally with a mixture of 2 mg CdCl₂ kg^?1, 20 mg DZN kg^?1 and 2 mg Na₂SeO₃ kg^?1 body weight and killed 36 h after xenobiotics had been injected. In the group B, young males (1-month-old) were administered with a combination of 30 mg CdCl₂ L^?1, 40 mg DZN L^?1 and 5 mg Na₂SeO₃ L^?1 in their drinking water, for 90 days. Ten 4-months-old males without toxicant supplementation served as a control group (C). After treatment period, detailed histological analysis of femoral bone was performed in each group. Our results revealed apparent osteoporotic symptoms (resorption lacunae, osteoporotic fractures) in rats from groups A and B. Moreover, histomorphometrical evaluation showed reduced bone vascularization (constricted primary osteons’ vascular canals and Haversian canals) and weakness mechanical properties of bones (smaller size of the secondary osteons) in these rats in comparison with those of the control group. Our study demonstrates for the first time that acute and subchronic co-administrations to Cd, DZN and Se induce evident manifestation characteristics of osteoporosis in male rats.     

Effect of in utero exposure to diethylstilbestrol on lumbar and femoral bone, articular cartilage, and the intervertebral disc in male and female adult mice progeny with and without swimming exercise

Introduction

Developmental exposure to estrogens has been shown to affect the musculoskeletal system. Furthermore, recent studies have shown that environmental exposure to estrogen-like compounds is much higher than originally anticipated. The aim of this study was to determine the effects of diethylstilbestrol (DES), a well-known estrogen agonist, on articular cartilage, intervertebral disc (IVD), and bone phenotype.

Methods

C57Bl/6 pregnant mice were dosed orally with vehicle (peanut oil) or 0.1, 1.0, and 10 μg/kg/day of DES on gestational days 11 to 14. Male and female pups were allowed to mature without further treatment until 3 months of age, when swim and sedentary groups were formed. After euthanasia, bone mineral density (BMD), bone mineral content (BMC), bone area (BA), and trabecular bone area (TBA) of the lumbar vertebrae and femur were measured by using a PIXImus Bone Densitometer System. Intervertebral disc proteoglycan was measured with the DMMB assay. Histologic analysis of proteoglycan for IVD and articular cartilage was performed with safranin O staining, and degeneration parameters were scored.

Results

The lumbar BMC was significantly increased in female swimmers at both the highest and lowest dose of DES, whereas the femoral BMC was increased only at the highest. The males, conversely, showed a decreased BMC at the highest dose of DES for both lumbar and femoral bone. The female swim group had an increased BA at the highest dose of DES, whereas the male counterpart showed a decreased BA for femoral bone. The TBA showed a similar pattern. Proteoglycan analysis of lumbar IVDs showed a decrease at the lowest doses but a significant increase at the highest doses for both males and females. Histologic examination showed morphologic changes of the IVD and articular cartilage for all doses of DES.

Conclusions

DES significantly affected the musculoskeletal system of adult mice. Results suggest that environmental estrogen contaminants can have a detrimental effect on the developmental lumbar bone growth and mineralization in mice. Further studies measuring the impact of environmental estrogen mimics, such as bisphenol A, are then warranted.     

Female attractiveness affects paternal investment: experimental evidence for male differential allocation in blue tits

Introduction

The differential allocation hypothesis (DAH) predicts that individuals should adjust their parental investment to their current mate??s quality. Although in principle the DAH holds for both sexes, male adjustment of parental investment has only been tested in a few experimental studies, revealing contradictory results. We conducted a field experiment to test whether male blue tits (Cyanistes caeruleus) allocate their parental effort in relation to female ornamentation (ultraviolet colouration of the crown), as predicted by the DAH.

Results

We reduced the UV reflectance in a sample of females and compared parental care by their mates with that of males paired to sham-manipulated control females. As predicted by the DAH our results demonstrate that males paired with UV-reduced females invested less in feeding effort but did not defend the chicks less than males paired with control females.

Conclusions

To our knowledge, this is one of the first studies providing support for male differential allocation in response to female ornamentation.     

The system of bony canals as the basis for the angioarchitectonics of bones]

The spatial interrelationships of osteon canals were studied in corrosion preparations with the help of rastral electron microscopy. The structure of microvessels, their belonging to a definite link of the microcirculatory bed, the interaction of vessels and their position with respect to the osseous matrix were studied in bone sections impregnated with silver nitrate after V. V. Kuprijanov. Haversian canals in the compact substance of the bone are longitudinally oriented, can duplicate and form a single system of canals. The neighbouring canals of osteons might be bound by means of Volkmann's canals. The investigation of the Haversian canals in serial sections has shown that the diameter of the same canals of osteons can change at different levels, the diameter of the osteons themselves remaining unchanged. This seems to speak of uneven development of osteons in their different parts. In the Haversian canal there are one-two or occasionally three vessels having all three links of the morphocirculatory bed. The course and ramification of the vessel are identical to the shape of the osteon canal which includes them. The vessels are closely connected with the bony matrix by means of connective tissue bundles directed from the canal wall to the vessel wall. These bundles appear to serve as a peculiar anchor or amortizing apparatus and its elasticity might be a factor of a change of the shape and direction of the canal vessels in the bone development process.     

Prediction of cortical bone elastic constants by a two-level micromechanical model using a generalized self-consistent method

A two-level micromechanical model of cortical bone based on a generalized self-consistent method was developed to take into consideration the transversely isotropic elasticity of many microstructural features in cortical bone, including Haversian canals, resorption cavities, and osteonal and interstitial lamellae. In the first level, a single osteon was modeled as a two-phase composite such that Haversian canals were represented by elongated pores while the surrounding osteonal lamellae were considered as matrix. In the second level, osteons and resorption cavities were modeled as multiple inclusions while interstitial lamellae were regarded as matrix. The predictions of cortical bone elasticity from this two-level micromechanical model were mostly in agreement with experimental data for the dependence of transversely isotropic elasticity of human femoral cortical bone on porosity. However, variation in cortical bone elastic constants was greater in experimental data than in model predictions. This could be attributed to variations in the elastic properties of microstructural features in cortical bone. The present micromechanical model of cortical bone will be useful in understanding the contribution of cortical bone porosity to femoral neck fractures.     

Histologic estimation of age at death using the anterior cortex of the femur

This report describes a new histologic method for determination of age at death, the latest in a series of studies that began with Kerley's pioneer presentation in 1965. The study population was collected from 328 documented individuals from an anatomy dissecting room in the United States, from two modern cemeteries in the Dominican Republic, and from autopsies performed in a Chilean hospital. Undecalcified thin sections 1.0 cm wide were made from specimens taken from the femoral midshaft directly opposite the linea aspera. Five 0.886 mm2 fields were located at the periosteal edge and photographed, mainly for purposes of defining the fields and providing a permanent record. Secondary osteons, type II osteons, osteon fragments, resorption spaces, and non-Haversian canals were recorded as number/mm2, and a 100-space grid was used to measure average percent of unremodeled, osteonal, and fragmental bone. Stepwise regression analysis of the measurements produced a series of regression equations for age estimation for females, males, and sexes combined. Most equations have a standard error of estimate of about 10 years, but the coefficients of determination (r2) range from 0.48 to 0.72. In practice, sex-specific equations gave better results than opposite-sex or nonspecific equations, mainly because males and females differed in the pattern of relations between osteons and osteon fragments with advancing age.     

Excitability decreasing central motor plasticity is retained in multiple sclerosis patients

Background

Essential tremor (ET) is one of the commonest movement disorders though the prevalence varies globally. There is paucity of data on ET prevalence in sub-Saharan Africa. The study aimed to determine the prevalence of ET in a Nigerian community.

Methods

This door-to-door survey was conducted in two stages. In Stage 1, 3000 randomly selected residents of an urban centre in Lagos, Nigeria, were screened using a questionnaire to detect symptoms of movement disorder. 234 participants who responded positively regarding presence of tremors were rescreened using an ET-specific questionnaire, a face-to-face interview and neurological examination. Diagnosis of ET was based on the Movement Disorders Society (MDS) consensus diagnostic criteria for ET.

Results

Of the 3000 participants, forty responded positively to the ET screening questionnaire, of which 36 (19 females and 17 males) had a final diagnosis of ET, giving a crude prevalence of 12 per 1000 (95% CI?=?8.1- 15.9). Gender specific prevalence was 10.3 /1000 in males and 14.3/1000 in females. Age specific prevalence increased with advancing age in both sexes. Age adjusted prevalence (WHO New world population) was 23.8 per 1000.

Conclusions

We documented a high prevalence of ET in this study, with typical increasing prevalence with advancing age as previously reported in other populations.     

Assessment of significance of features acquired from thyroid ultrasonograms in Hashimoto's disease

Background

Most studies on biodegradable magnesium implants published recently use magnesium-calcium-alloys or magnesium-aluminum-rare earth-alloys. However, since rare earths are a mixture of elements and their toxicity is unclear, a reduced content of rare earths is favorable. The present study assesses the in vivo biocompatibility of two new magnesium alloys which have a reduced content (ZEK100) or contain no rare earths at all (AX30).

Methods

24 rabbits were randomized into 4 groups (AX30 or ZEK100, 3 or 6 months, respectively) and cylindrical pins were inserted in their tibiae. To assess the biodegradation ??CT scans and histological examinations were performed.

Results

The ??CT scans showed that until month three ZEK100 degrades faster than AX30, but this difference is leveled out after 6 months. Histology revealed that both materials induce adverse host reactions and high numbers of osteoclasts in the recipient bone. The mineral apposition rates of both materials groups were high.

Conclusions

Both alloys display favorable degradation characteristics, but they induce adverse host reactions, namely an osteoclast-driven resorption of bone and a subsequent periosteal formation of new bone. Therefore, the biocompatibility of ZEK100 and AX30 is questionable and further studies, which should focus on the interactions on cellular level, are needed.     

The peroxisome proliferator-activated receptor (PPAR) alpha agonist fenofibrate maintains bone mass, while the PPAR gamma agonist pioglitazone exaggerates bone loss, in ovariectomized rats

Background

Activation of peroxisome proliferator-activated receptor (PPAR)gamma is associated with bone loss and increased fracture risk, while PPARalpha activation seems to have positive skeletal effects. To further explore these effects we have examined the effect of the PPARalpha agonists fenofibrate and Wyeth 14643, and the PPARgamma agonist pioglitazone, on bone mineral density (BMD), bone architecture and biomechanical strength in ovariectomized rats.

Methods

Fifty-five female Sprague-Dawley rats were assigned to five groups. One group was sham-operated and given vehicle (methylcellulose), the other groups were ovariectomized and given vehicle, fenofibrate, Wyeth 14643 and pioglitazone, respectively, daily for four months. Whole body and femoral BMD were measured by dual X-ray absorptiometry (DXA), and biomechanical testing of femurs, and micro-computed tomography (microCT) of the femoral shaft and head, were performed.

Results

Whole body and femoral BMD were significantly higher in sham controls and ovariectomized animals given fenofibrate, compared to ovariectomized controls. Ovariectomized rats given Wyeth 14643, maintained whole body BMD at sham levels, while rats on pioglitazone had lower whole body and femoral BMD, impaired bone quality and less mechanical strength compared to sham and ovariectomized controls. In contrast, cortical volume, trabecular bone volume and thickness, and endocortical volume were maintained at sham levels in rats given fenofibrate.

Conclusions

The PPARalpha agonist fenofibrate, and to a lesser extent the PPARaplha agonist Wyeth 14643, maintained BMD and bone architecture at sham levels, while the PPARgamma agonist pioglitazone exaggerated bone loss and negatively affected bone architecture, in ovariectomized rats.     

Effect of cyclic loading on the nanoscale deformation of hydroxyapatite and collagen fibrils in bovine bone

Cyclic compressive loading tests were carried out on bovine femoral bones at body temperature $(37\,^{\circ }\hbox {C})$ , with varying mean stresses ( $-55$ to $-80$  MPa) and loading frequencies (0.5–5 Hz). At various times, the cyclic loading was interrupted to carry out high-energy X-ray scattering measurements of the internal strains developing in the hydroxyapatite (HAP) platelets and the collagen fibrils. The residual strains upon unloading were always tensile in the HAP and compressive in the fibrils, and each increases in magnitude with loading cycles, which can be explained from damage at the HAP–collagen interface and accumulation of plastic deformation within the collagen phase. The samples tested at a higher mean stress and stress amplitude, and at lower loading frequencies exhibit greater plastic deformation and damage accumulation, which is attributed to greater contribution of creep. Synchrotron microcomputed tomography of some of the specimens showed that cracks are produced during cyclic loading and that they mostly occur concentric with Haversian canals.     

Ovariectomy and overeating palatable, energy-dense food increase subcutaneous adipose tissue more than intra-abdominal adipose tissue in rats

Background

Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that macrophages in the spleen are phenotypically distinct in male compared to female mice at 12 h after infection. This innate immune profile mirrors and predicts the cardiac immune response during acute myocarditis.

Methods

In order to study sex differences in the innate immune response, five male and female BALB/c mice were infected intraperitoneally with coxsackievirus B3 (CVB3) or phosphate buffered saline and their spleens were harvested 12 h later for microarray analysis. Gene expression was determined using an Affymetrix Mouse Gene 1.0 ST Array. Significant gene changes were verified by quantitative real-time polymerase chain reaction or ELISA.

Results

During the innate immune response to CVB3 infection, infected males had higher splenic expression of genes which are important in regulating the influx of cholesterol into macrophages, such as phospholipase A₂ (PLA₂) and the macrophage scavenger receptor compared to the infected females. We also observed a higher expression in infected males compared to infected females of squalene synthase, an enzyme used to generate cholesterol within cells, and Cyp2e1, an enzyme important in metabolizing cholesterol and steroids. Infected males also had decreased levels of the translocator protein 18 kDa (TSPO), which binds PLA₂ and is the rate-limiting step for steroidogenesis, as well as decreased expression of the androgen receptor (AR), which indicates receptor activation. Gene differences were not due to increased viral replication, which was unaltered between sexes.

Conclusions

We found that, compared to females, male mice had a greater splenic expression of genes which are important for cholesterol metabolism and activation of the AR at 12 h after infection. Activation of the AR has been linked to increased cardiac hypertrophy, atherosclerosis, myocarditis/DCM and heart failure in male mice and humans.     

The 5.5-year results of MegaOATS – autologous transfer of the posterior femoral condyle: a case-series study

Introduction

Large osteochondral defects of the weight-bearing zones of femoral condyles in young and active patients were treated by autologous transfer of the posterior femoral condyle (large osteochondral autogenous transplantation system (MegaOATS)). The technique presented is a sound and feasible salvage procedure to address large osteochondral defects in weight-bearing zones.

Methods

Thirty-six patients between July 1996 and December 2000 were included. Thirty-three patients (10 females, 23 males) were evaluated by the Lysholm score and X-ray scans. A random sample of 16 individuals underwent magnetic resonance imaging analysis. The average age at the date of surgery was 34.3 (15 to 59) years, and the mean follow up was 66.4 (46 to 98) months. The mean defect size was 6.2 (2 to 10.5) cm², in 27 patients affecting the medial femoral condyle and in six patients affecting the lateral femoral condyle. Trauma or osteochondrosis dissecans were pathogenetic in 82%.

Results

The Lysholm score in all 33 individuals showed a highly significant increase from a preoperative median 49.0 points to a median 86.0 points (P ≤ 0.001). Twenty-seven patients returned to recreational sports. X-ray scans showed a rounding of the osteotomy edge in 24 patients, interpreted as a partial remodelling of the posterior femoral condyle. Preoperative osteoarthritis in 17 individuals was related to significant lower Lysholm scores (P = 0.014), but progression in 17 patients did not significantly influence the score results (P = 0.143). All 16 magnetic resonance imaging examinations showed vital and congruent grafts.

Conclusion

Patients significantly improve in the Lysholm score, in daily-life activity levels and in return to recreational sports. Thirty-one out of 33 patients were comfortable with the results and would undergo the procedure again. The MegaOATS technique is therefore recommended as a salvage procedure for young individuals with large osteochondral defects in the weight-bearing zone of the femoral condyle.     

Surfactant Protein D modulates allergen particle uptake and inflammatory response in a human epithelial airway model

Background

The obese-asthma phenotype is not well defined. The aim of this study was to examine both mechanical and inflammatory influences, by comparing lung function with body composition and airway inflammation in overweight and obese asthma.

Methods

Overweight and obese (BMI 28-40 kg/m²) adults with asthma (n = 44) completed lung function assessment and underwent full-body dual energy x-ray absorptiometry. Venous blood samples and induced sputum were analysed for inflammatory markers.

Results

In females, android and thoracic fat tissue and total body lean tissue were inversely correlated with expiratory reserve volume (ERV). Conversely in males, fat tissue was not correlated with lung function, however there was a positive association between android and thoracic lean tissue and ERV. Lower body (gynoid and leg) lean tissue was positively associated with sputum %neutrophils in females, while leptin was positively associated with android and thoracic fat tissue in males.

Conclusions

This study suggests that both body composition and inflammation independently affect lung function, with distinct differences between males and females. Lean tissue exacerbates the obese-asthma phenotype in females and the mechanism responsible for this finding warrants further investigation.     

Treatment of growth plate injury with microencapsulated chondrocytes

Background

Tissue-engineered cartilage has provided a promising method in the treatment of physeal growth arrest. This study was designed to investigate transplantation of microencapsulated allogeneic chondrocytes to treat the injured growth plate.

Methods

Allogeneic chondrocytes were encapsulated within alginate-polylysinealginate semipermeable membranes. Microencapsulated chondrocytes co-cultured with Bone Mesenchymal Stem Cells (BMSCs) were evaluated whether it could promote chondrogenesis of BMSCs. An experiment model of an injured growth plate was made by resecting the lateral half of the right distal femur physis in rabbits. Microencapsulated allogeneic chondrocytes, allogeneic chondrocytes as well as empty microcapsules were grafted into growth plate defects of 6-week-old rabbits. Histological and radiographic examinations were examined after transplantation up to 16 weeks.

Results

The histological study showed that BMSCs co-cultured with microencapsulated chondrocytes could produce GAG and II collagen similarly with chondrocytes. Angular deformity and length discrepancy in the group with microencapsulated allogeneic chondrocytes were less than those in other groups (p < 0.001). The histological study confirmed the viability of microencapsulated chondrocytes at 16 weeks postoperatively. The neogenetic chondrocytes of columnar arrangement have been found in the growth plate defect to prevent early ossification and closure of the growth plate.

Conclusions

The histological study confirmed the viability of microencapsulated chondrocytes at 16 weeks postoperatively. The neogenetic chondrocytes of columnar arrangement have been found in the growth plate defect to prevent early ossification and closure of the growth plate.