Pregnant type 1 diabetes women with rises in C-peptide display higher levels of regulatory T cells: A pilot study.

AIM: During pregnancy of type 1 diabetes (T1D) women, a C peptide rise has been described, which mechanism is unclear. In T1D, a defect of regulatory T cells (Tregs) and its major controlling cytokine, interleukin-2 (IL2), is observed. METHODS: Evolution of clinical, immunological (Treg (CD4+CD25hiCD127-/loFoxp3+ measured by flow cytometry and IL2 measured by luminex xMAP technology) and diabetes parameters (insulin dose per day, HbA1C, glycaemia, C peptide) was evaluated in 13 T1D women during the three trimesters of pregnancy and post-partum (PP, within 6 months) in a monocentric pilot study. Immunological parameters were compared with those of a healthy pregnant cohort (QuTe). RESULTS: An improvement of beta cell function (C peptide rise and/or a decrease of insulin dose-adjusted A1c index that estimate individual exogenous insulin need) was observed in seven women (group 1) whereas the six others (group 2) did not display any positive response to pregnancy. A higher level of Tregs and IL2 was observed in group 1 compared to group 2 during pregnancy and at PP for Tregs level. However, compared to the healthy cohort, T1D women displayed a Treg deficiency CONCLUSION: This pilot study highlights that higher level of Tregs and IL2 seem to allow improvement of endogenous insulin secretion of T1D women during pregnancy.

Autoradiographic study of neurosteroid binding sites labelled with [35S]-TBPS in brain of different species.

Distribution of [35S]-TBPS binding sites was studied in various structures of brain in mouse and guinea pig and in cortex of monkey and in hippocampus of postmortem human brain. As it is observed for rat brain, high densities of [35S]-TBPS binding sites were found in layer IV of cortex in the four species, and in thalamus of mouse and guinea pig. Intermediate densities of binding sites were observed in superficial and deep layers of cortex in those four species and in hippocampus of mouse, guinea pig, and human. In all brain structures studied, 5 alpha 3 alpha P and picrotoxin produced a dose-dependent inhibition of [35S]-TBPS binding. No significant interregion or interspecies differences could not be detected for IC50 values of 5 alpha 3 alpha P or picrotoxin to inhibit [35S]-TBPS from its binding sites. In all regions studied, IC50 values were close to 1.5 x 10(-6) M for 5 alpha 3 alpha P and 2.3 x 10(-7) M for picrotoxin.

Hyperparathyroidism in proximal femur fractures biological and histomorphometric study in 21 patients over 75 years old.

Proximal femur fractures in elderly people are more and more frequent. Falls and senile bone disorders are the risk factors of this fracture. In order to understand the mechanisms of these bone disorders, we studied 21 consecutive patients with this fracture using bone histomorphometry. Measurements of serum intact parathormone (PTH), 25-(OH)-vitamin D, 1,25-(OH) 2-vitamin D and osteocalcin have been performed in these 21 patients, included in a larger series. We excluded patients with renal failure (serum creatinine greater than 140 mumols/l), cancer, or previous metabolic bone disease. There were 19 female and 2 male patients, ranging from 75 to 96 years, (mean 84.9). We found a low frequency of cortical (2/21) and trabecular (3/21) osteoporosis. There was no case of clearcut osteomalacia. Following histomorphometric bone study, two patients showed a typical pattern of hyperparathyroidism, and in a third one, this condition seemed very likely. In these three patients who were among the oldest, and who had high levels of serum PTH, chronic renal failure and primary hyperparathyroidism could be excluded. High bone remodeling was frequent in our patients, as reflected by the enhancement of eroded surfaces (13 cases) and of osteoid thickness (7 cases). Intact PTH level was elevated in our series compared to normal values in adults (in accordance to the PTH elevation in the case control study in a larger series). These findings suggest a major role of a secondary hyperparathyroidism in senile bone disorders favoring proximal femur fractures. This hyperparathyroidism is probably secondary to mild calcium and vitamin D deficiency. It may lead to architectural bone changes favoring this fracture.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hypophyseal surgical treatment of Cushing's disease in the child]. / Le traitement chirurgical hypophysaire de la maladie de Cushing chez l'enfant.

Cushing's disease in children is rare and not familar to pediatricians. We report here 7 cases concerning children between 8 and 16 years of age, treated by pituitary surgery with 1 to 9 year follow-up. A remission of hypercorticism was obtained in all cases. However, a pituitary deficiency requiring replacement opotherapy and/or a recurrence was observed in 5 out of 7 patients. From our experience and the review of literature (around 130 cases), Cushing's disease is more serious in children than in adult. We suggest therapeutic management with transsphenoidal surgery as the treatment of choice. Given the frequency of recurrence (13 à 54%) often late (9-12 years), we stress the need of regular and extended postoperative follow-up.

[Phosphorus-calcium metabolism in hyperthyroidism]. / Etude du métabolisme phospho-calcique dans l'hyperthyroïdie.

Because of the bone remodelling it induces, hyperthyroidism modifies the parameters of calcium-phosphorus metabolism. For a better determination of the mechanism involved, we studied 13 patients with Graves' disease compared with 13 controls. We measured the various parameters of calcium-phosphorus metabolism, notably the levels of parathormone, 25-hydroxycholecalciferol, 1-25 dihydroxycholecalciferol and ostocalcin; 8 patients were re-examined in euthyroidism. Total and corrected values of calcaemia (P less than 0.05 and P less than 0.01), phosphoreamie (P less than 0.01), alkaline phosphatase (P less than 0.01), calciuria (P less than 0.01) and hydroxyprolinuria (P less than 0.01) were significantly higher in patients with hyperthyroidism. Osteocalcin also was significantly increased (P less than 0.01) and correlated with thyroid hormone levels, thus confirming its usefulness as marker of bone remodelling in hyperthyroidism. Creatininaemia was significantly lowered (P less than 0.01). The intestinal absorption of calcium after injection of 1 g of calcium was reduced. Parathormone and 25-hydroxycholecalciferol levels were not significantly different in patients and in controls. In patients who were re-examined in euthyroidism, there was a significant increase in parathormone and in 1-25 dihydroxycholecalciferol levels (P less than 0.05). Thus, in situations of hyperthyroidism 2 elements contribute to a deficit in calcium balance: (a) a fall in parathormone level, consecutive to a rise in calcaemia, induces hypercalciuria; and (b) a fall in 1-25 dihydroxycholecalciferol level, consecutive to functional hypoparathyroidism and hyperphosphoraemia, results in a decrease of intestinal calcium absorption.