Validity and reliability of the Farsi version of the ECOS-16 questionnaire for females with osteoporosis.

The purpose of this study was to develop a Persian version of ECOS-16 Questionnaire and assess its reliability and validity. Two hundred and twenty women with postmenopausal osteoporosis were included in the study. Patients who were diagnosed as secondary osteoporosis by clinical and laboratory examinations were excluded. For reliability, an internal consistency (Cronbach's alpha coefficient) of ECOS-16 total score was calculated. The age of the study participants ranged from 50 to 75 years old (59.9 ± 7). Cronbach's alpha of the Persian version of the ECOS-16 was 0.84. Therefore, the Persian version of the ECOS-16 is a reliable and valid questionnaire to be used in the evaluation of quality of life in women with postmenopausal osteoporosis.

Hypothalamic ATP-sensitive K + channels play a key role in sensing hypoglycemia and triggering counterregulatory epinephrine and glucagon responses.

It has been postulated that specialized glucose-sensing neurons in the ventromedial hypothalamus (VMH) are able to detect falling blood glucose and trigger the release of counterregulatory hormones during hypoglycemia. The molecular mechanisms used by glucose-sensing neurons are uncertain but may involve cell surface ATP-sensitive K(+) channels (K(ATP) channels) analogous to those of the pancreatic beta-cell. We examined whether the delivery of sulfonylureas directly into the brain to close K(ATP) channels would modulate counterregulatory hormone responses to either brain glucopenia (using intracerebroventricular 5-thioglucose) or systemic hypoglycemia in awake chronically catheterized rats. The closure of brain K(ATP) channels by global intracerebroventricular perfusion of sulfonylurea (120 ng/min glibenclamide or 2.7 microg/min tolbutamide) suppressed counterregulatory (epinephrine and glucagon) responses to brain glucopenia and/or systemic hypoglycemia (2.8 mmol/l glucose clamp). Local VMH microinjection of a small dose of glibenclamide (0.1% of the intracerebroventricular dose) also suppressed hormonal responses to systemic hypoglycemia. We conclude that hypothalamic K(ATP) channel activity plays an important role in modulating the hormonal counterregulatory responses triggered by decreases in blood glucose. Our data suggest that closing of K(ATP) channels in the VMH (much like the beta-cell) impairs defense mechanisms against glucose deprivation and therefore could contribute to defects in glucose counterregulation.

Role of corticotrophin-releasing hormone in the impairment of counterregulatory responses to hypoglycemia.

We have explored the role of individual elements of the hypothalamic pituitary adrenal axis on the pathogenesis of hypoglycemia-associated autonomic failure. Five groups of male Sprague-Dawley rats were used. Control animals had 3 days of sham treatment followed by a hyperinsulinemic/hypoglycemic glucose clamp on day 4. A second group underwent 3 days of antecedent insulin-induced hypoglycemia then a subsequent clamp. Three more groups underwent pretreatment with corticosterone, adrenocorticotrophic hormone (ACTH), or corticotrophin-releasing hormone (CRH) mirroring the glucocorticoid response of the hypoglycemic group. Subsequent counterregulatory responses showed marked differences. CRH- (and insulin-treated) animals showed markedly reduced epinephrine responses (CRH 1,276 +/- 404 pg/ml, controls 3,559 +/- 563 pg/ml; P < 0.05). In contrast, ACTH pretreatment augmented epinephrine responses (6,681 +/- 814 pg/ml; P = 0.007 versus controls); corticosterone pretreatment caused a similar but nonsignificant enhancement. The same pattern was seen for norepinephrine. CRH pretreatment also suppressed glucagon responses to hypoglycemia (control 157 +/- 21, CRH 68 +/- 10 pg/ml; P = 0.004). The addition of a CRH receptor 1 (CRHr1) antagonist to the antecedent CRH reversed the subsequent suppression of epinephrine. These findings suggest that CRH acting via CRHr1 plays an important role in the sympathoadrenal downregulation seen in this rodent model of antecedent hypoglycemia; this action is not mediated via activation of the hypothalamic-pituitary-adrenal axis.