Secretory activity of the brain and peripheral organs: Spontaneous and stimulated release of noradrenaline in the ontogenesis of rats.

Spontaneous and K(+)-stimulated release of noradrenaline from the hypothalamus, adrenal gland, and organ of Zuckerkandl under their flowing incubation was investigated in the perinatal period of ontogenesis of rats. The results suggest that, during the investigated period of ontogenesis, adrenal glands are the main source of noradrenaline in the blood, whereas the contributions of the organ of Zuckerkandl and the brain are not as significant and change during this period.

Para-aortic involvement and interest of para-aortic lymphadenectomy after chemoradiation therapy in patients with stage IB2 and II cervical carcinoma radiologically confined to the pelvic cavity.

BACKGROUND: Pelvic radiation therapy with concomitant chemotherapy (PCRT) is the standard treatment of stage IB2/II cervical carcinoma. The impact of concomitant chemotherapy on positive para-aortic nodes (PA+), however, remains unknown. The aim of this study was twofold: to evaluate the rate of histological PA+ after PCRT and to determine the survival of patients with PA+. METHODS: Patients fulfilling the following inclusion criteria were studied: (1) stage IB2/II cervical carcinoma, (2) histological subtype: squamous cell, adenocarcinoma or an adenosquamous tumor, (3) exclusion of patients with radiological PA+ (CT scan/MRI), (4) pelvic external radiation therapy of 45 Gy with concomitant chemotherapy (cisplatin 40 mg/m2/week) + utero-vaginal brachytherapy, and (5) completion surgery after the end of PCRT including at least a para-aortic lymphadenectomy. RESULTS: Seventy-three patients (16 stage IB2, 57 stage II) treated between 1998 and 2004 fulfilled all the inclusion criteria. PA+ after PCRT were observed in 13 patients (18%) with a median of five (range, 2-22) positive nodes. Overall and disease-free survival at 24 months in patients with PA+ was 40% and 17%. Only two patients with PA+ are currently alive and in remission. CONCLUSIONS: The rate of PA+ remains high after PCRT in patients treated for stage IB2/II cervical carcinoma. Furthermore, the survival rate of patients with PA+ is very low. These important results suggest that detection of PA + at the time of completion surgery (after PCRT) is not beneficial for improving survival.

Treatment outcomes of extended-field radiation therapy and the effect of concurrent chemotherapy on uterine cervical cancer with para-aortic lymph node metastasis.

PURPOSE: To review the clinical outcomes of extended-field radiation therapy (EFRT) and to analyze prognostic factors significant for survival in patients receiving EFRT for uterine cervical carcinoma with para-aortic node (PAN) metastasis. PATIENTS AND METHODS: We retrospectively reviewed 90 patients with stage IB-IVA cervical cancer and PAN metastasis between 1987 and 2012. Median age was 50 (range, 24-77). Patients received median 70.2 Gy (range, 56-93) to point A and median 50.4 Gy (range, 45-60.4) to PAN over median 69 elapsed days (range, 43-182). Forty-six patients (51.1%) received concurrent chemotherapy. Survival was calculated using the Kaplan-Meier method. We analyzed prognostic factors for overall actuarial survival (OS) and progression-free survival (PFS) using a Cox regression method. RESULTS: The median follow-up period for surviving patients was 55 months (range, 3-252). Seventy patients (77.8%) had complete remission. Forty-six patients experienced treatment failure as follows: 11 patients (12.2%) as local recurrence, 19 (21%) as regional recurrence and 33 (36.7%) as distant metastasis. The 5-yr OS and PFS were 62.6% and 43.9%, respectively. Treatment response was the only statistically independent prognostic factors for OS (p= 0.04) and PFS (p< 0.001) on multivariate analysis. Grade 3 or 4 hematologic gastrointestinal and urogenital toxicities were observed in about 10% of patients. CONCLUSIONS: Our institutional experiences showed that EFRT was an effective treatment for cervical cancer patients with PAN metastasis. The addition of chemotherapy to EFRT seems to have uncertain survival benefit with higher hematologic toxicity.

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.

The effect of hydrocortisone on the para-aortic body of the newborn mouse: an in vivo fraction of labelled mitoses study.

Information about the cell cycle of the mouse para-aortic body within the first 24 hours of postnatal life was derived from a fraction of labelled mitoses study. The total cell cycle time was 8 1/2 hours, being made up as follows: S phase-2 hours; G2 phase-1 hour; M phase-3 1/2 hours (by analysis of the results, not by assumption) and G1 phase-2 hours (by subtraction). Problems are discussed regarding the length of G2 and M phases and the consequences for G1. After hydrocortisone administration (40 mg/kg/day) to female mice for the last seven days of pregnancy, the pattern in newborn mice was disrupted. Values for G2 and M were similar to those of the untreated group, but no values were obtainable for the other phases of the cell cycle or for the total cell cycle time. These results after hydrocortisone treatment could be explained by the superimposition of the cell cycles of two or more different groups of cells. They are discussed with regard to the life span of the para-aortic body, and their implications are considered in the light of previously reported glucocorticoid-induced transformations of small granule cells from cervical sympathetic ganglia into catecholamine-storing chromaffin cells. The established hyperplastic effect of hydrocortisone on the para-aortic body is therefore not the result simply of an acceleration of the cell cycle, but it may involve the incorporation into the proliferative compartment of cells previously either moribund or nonproliferating.

The effect of in vivo hydrocortisone administration on the labelling index and size of the intra- and extra-adrenal chromaffin tissue of the fetal and perinatal mouse.

Administration of hydrocortisone in vivo to pregnant mice between the eighth and sixteenth days of gestation leads to highly significant increases in both the volume and the labelling index of extra-adrenal chromaffin tissue (as represented by the para-aortic body) of 16 days fetal mice. The labelling index of intra-adrenal chromaffin cells increases slightly after hydrocortisone administration, but the volume of the adrenal chromaffin tissue was not assessed since the groups of chromaffin cells had not in all cases aggregated to form a distinct medulla. Hydrocortisone administration to mice for the last week of gestation also leads to a highly significant increase in the size and the labelling index of the perinatal para-aortic body. Although an increase in the labelling index of perinatal intra-adrenal chromaffin cells is brought about, this is much less marked than that of the extra-adrenal tissue and neither is it reflected by any increase in the volume of the now discernible adrenal medulla. These increases in size and labelling index of the para-aortic body constitute a hyperplastic response rather than a hypertrophic response. Various possible mechanisms and implications are discussed in the light of the development of chromaffin tissue and the effects of the cortex and its secretions on the medulla. Associated effects of hydrocortisone noted in this work are the resultant marked diminution of adrenocortical volume in the perinatal gland, and a slight fall in the labelling index of perinatal intra-adrenal haemopoietic cells.

The effect of in vivo hydrocortisone administration on the labelling index and size of chromaffin tissue in the postnatal and adult mouse.

Hydrocortisone administration in vivo to neonatal mice for seven days led to a significant increase in both the size and the labelling index of extra-adrenal chromaffin tissue (as represented by the para-aortic body) of 8 days old mice. In untreated animals at this age, the para-aortic body was in most cases too small to obtain a valid labelling index. In the para-aortic bodies of 14 days old, 21 days old and adult mice, the extra-adrenal chromaffin tissue was too dispersed to obtain values for either volumetric analysis or labelling indices, and hydrocortisone was without significant effect in promoting a hyperplastic response. In the postnatal adrenal medulla at all ages studied, hydrocortisone had no effect on the medullary size or on the labelling indices of either adrenaline- or noradrenaline-storing cells, although it led to a marked diminution of adrenocortical volume. The relative proportion of adrenaline-storing cells increased between the values for 8 days old animals and those for adults; this was unaffected by hydrocortisone. The cortico-medullary ratio remained unchanged from the eighth postnatal day onwards. The results are discussed and related to those of other workers. It is suggested that factors as yet unknown might modulate the response to corticosteroids of developing intra- and extra-adrenal chromaffin tissue.