Morphophysiology of the Zuckerkandl's paraganglion: effects of dexamethasone and aging.

The extra-adrenal Zuckerkandl's paraganglion is used as a source of chromaffin cells for transplantation in parkinsonian animals. Aging can affect its viability, and this tissue needs further characterization for improving grafting procedures. The objectives were: (i) to compare the main morpho-functional characteristics of prepubertal and old Zuckerkandl's paraganglion (ZP), and (ii) to discern phenotypic changes after sub-chronic dexamethasone treatment in extra-adrenal tissue of prepubertal rats. For these purposes, immunostaining methods, stereology, voltammetry, cell culture, Western blotting, and ELISA were employed. The findings revealed that all paraganglia were composed of mesenchymal tissue and chromaffin cells. In prepubertal rats, chromaffin cells are arranged as large or small clusters. Large clusters (also known as "cell nests") contain densely packed chromaffin cells, and they are seen as fascicles in longitudinal sections. In old paraganglia, cell nests disappear, and chromaffin cells are found to be arranged as small cell clusters or dispersed throughout the mesenchyma. Paraganglionic chromaffin cells possess a rounded morphology with diameter ranging from 12 to 15 µm, with intracytoplasmic granules (100-500 nm in diameter) containing catecholamines. Prepubertal and old ZP chromaffin cells are mostly noradrenergics, and a few of them are dopaminergics. Aging reduces the amount of chromaffin tissue (28% in adult rats vs. 11% in old animals, both in relation to total volume of the paraganglion), and induces the presence of adrenergic cells and adrenaline. Both prepubertal and old cells express the neurotrophic factors GDNF and TGF-ß1, aging leading to reduced levels of both growth factors. Dexamethasone (50 µg/kg daily, 5 days) leads to the expression of phenylethanolamine-N-methyl-transferase in prepubertal paraganglia, and to a higher content and release of adrenaline.

Grafts of extra-adrenal chromaffin cells as aggregates show better survival rate and regenerative effects on parkinsonian rats than dispersed cell grafts.

The objective was to discern the neuroregenerative effect of grafts of extra-adrenal cells of the Zuckerkandl's paraganglion (ZP) in the nigrostriatal circuit, by using the retrograde model of parkinsonism in rats. The antiparkinsonian efficacy of two types of grafting procedures was studied (cell aggregates vs. dispersed cells), and GDNF and TGFbeta(1) (dopaminotrophic factors) as well as dopamine presence in extra-adrenal tissue was analyzed. Extra-adrenal chromaffin cells are noradrenergics, tissue dopamine is low, and they express both GDNF and TGFbeta(1). Grafts of cell aggregates, not of dispersed cells, exerted a trophic regeneration of the host striatum, leading to amelioration of motor deficits. Sprouting of spared dopaminergic fibers within the striatum, reduction of dopamine axon degeneration, and/or enhanced phenotypic expression of TH would explain striatal regeneration. Grafted cells as aggregates showed a better survival rate than dispersed cells, and they express higher levels of GDNF. Higher survivability and GDNF content together with the neurorestorative and dopaminotrophic action of both GDNF and TGFbeta(1) could account for striatal recovery and functional amelioration after grafting ZP cell aggregates. Finally, nigral degeneration and partial degeneration of ventral tegmental area were not precluded after transplantation, indicating that the trophic effect of grafts was local within the host striatum.

Quantitative ultrasound in adults with cystic fibrosis: correlation with bone mineral density and risk of vertebral fractures.

In several conditions, including cystic fibrosis (CF) and corticosteroid-induced osteoporosis, bone mineral density (BMD) measurements provide a modest prediction of fracture risk. We investigated in adult CF patients whether quantitative ultrasound (QUS) parameters were able to discriminate between patients with and without prevalent vertebral fractures. One hundred seventy-two adults with CF, 91 men and 81 women, often on chronic oral or inhaled corticosteroid therapy, were studied. BMD at the lumbar spine, proximal femur, and total body were measured by dual-energy X-ray absorptiometry (DXA). QUS parameters were assessed by Achilles Express at the calcaneus and by the DBM Sonic 1200 at the phalanges. All bone measurements by DXA and QUS were significantly correlated with each other, with the exception of phalangeal amplitude-dependent speed of sound versus spine BMD. The mean T-score values in CF patients with and without prevalent vertebral fractures were similar for all DXA measurements and for stiffness index. A significant difference between the two groups was observed only for phalangeal ultrasound bone profile index (UBPI) values (relative risk = 1.25, 95% confidence interval 1.05-1.49 for each decrease in T score), and this difference was maintained after adjusting the values for age, body weight, forced expiratory volume in 1 second, gender, and corticosteroid use. In conclusion, only a phalangeal QUS parameter (UBPI), in contrast with calcaneus QUS or DXA measurements, was able to discriminate CF patients with from those without vertebral fractures, possibly as a result of qualitative alterations of bone tissue independent of BMD.

Prevalence and correlates of vertebral fractures in adults with cystic fibrosis.

INTRODUCTION: Osteoporosis associated with cystic fibrosis (CF) is becoming increasingly important as the life expectancy of patients continues to increase. MATERIALS AND METHODS: We studied 191 adults with CF (18-50 years old; 100 men, 91 women). Total body, lumbar spine, and total proximal femur bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry, and lateral spinal radiographs were taken for assessment of vertebral fractures. A range of anthropometric, clinical and biochemical variables were evaluated as potential correlates. RESULTS: BMD T score values at the lumbar spine lower than -2.5 SD were observed in 27.3% and 11.2% of male and female patients, respectively. These proportions fell to 14% and 9.9% for total hip and 10.4% and 12.1% for total body, in men and women, respectively. Vertebral deformities were identified in 26.7% of the patients with a slightly higher prevalence in males (32%) than in females (21%, P = 0.058). Multiple vertebral deformities were observed in 12% and 7.7% of men and women, respectively. BMD values were significantly related to body weight, FEV1, age of puberty and occasionally to cumulative steroid dose in both genders. BMD values were also significantly related with serum albumin, IgG and cholinesterase. Serum estradiol levels were found below the normal range in 23% of the women and 27% of the men, and was significantly related to femur BMD values in both women and men. Significantly lower serum estradiol and free testosterone levels were observed in men with vertebral fractures. Serum osteocalcin was below the normal range in 36% and urinary deoxypyridinoline above the normal range in 51% of the patients. CONCLUSIONS: This study indicates that osteoporosis is a common complication of CF, being related to disease progression and apparently due to both excess bone resorption and inadequate bone formation. Estradiol deficiency may have a significant role in the pathogenesis in both genders. Vertebral fracture prevalence is high and greater than expected from prevalent BMD values.

Observations of growth plate development in achondroplastic (cn/cn) mice.

The autosomal recessive gene for achondroplasia (cn) in the homozygous condition inhibits the growth of the cartilaginous skeleton in mice. Changes in the width of the proximal growth plate of the tibia and the caudal vertebrae and in the number of proliferative and hypertrophic cells were recorded in normal and achondroplastic (cn/cn) mice during the first 30 neonatal days. In normal mice as in achondroplastics, the width of the cartilaginous growth plate decreased progressively with increasing age. The proliferative zone of cn/cn mice was similar in structure to that of normal mice and showed no significant difference. Hypertrophied cartilage was less wide and there were fewer hypertrophic cells at the epiphyseal plates than found in normal mice. The data of the present study show that retarded longitudinal bone growth in cn/cn mice is due to reduced hypertrophy of the chondrocytes.