1,720,976 research outputs found
Electrophysiological effects of a pumiliotoxin-B-like alkaloid derived from the skin of the Australian frog Pseudophryne coriacea.
No full textSkin extracts of the Australian frog Pseudophryne coriacea (PsC) potentiate and prolong the bioelectric activity of various excitable tissues. When studied by electrophysiological means in a preparation of mouse diaphragm, PsC skin extracts did not affect the spontaneous acetylcholine (ACh) release. However, the indirect stimulation of the preparation in the presence of PsC skin extracts gave rise to a different profile of rhythmic activity showing afterpotentials and variable oscillatory activity. The action potential and the total sodium current recorded in the muscle fibre with the loose patch clamp method were not modified significantly by the alkaloid. Concentrations of PsC skin extract that did not cause repetitive activity, seemed to reduce slightly the quantal content of the evoked release of ACh. The resting potential of muscle fibres was not modified even by the highest PsC skin extract concentrations. These results suggest that the facilitation effects of PsC skin extracts could be due to intracellular mechanisms probably related to the control of the cytosolic calcium concentrations or to an increased excitability of the presynaptic biomembranes
Association of glucocorticoid receptor polymorphism A3669G with decreased risk of developing diabetes in patients with Cushing's syndrome
No full textObjective
Glucocorticoid receptor (GR) polymorphisms alter glucocorticoid (GC) sensitivity and have been associated with altered metabolic profiles. We evaluate the prevalence of the four GR (NR3C1) polymorphisms BclI, N363S, ER22/23EK, and A3669G in patients with Cushing's syndrome (CS) compared with healthy controls (HC) and we investigate their role in the development of metabolic abnormalities in patients with CS according to their hormonal profile.
Patients and methods
Sixty-one patients with CS and 71 sex- and age-matched HC were genotyped.
Results
BclI variant was markedly higher in patients with CS compared with HC (62 vs 41%, P<0.05) while no significant differences were found among other polymorphisms. A very low frequency of N363S and the ER22/23EK was observed.
In CS patients, despite the significantly increased levels of morning serum cortisol in BclI carriers compared with wild type no clinical or metabolic differences were found.
In contrast, A3669G GR carriers showed a significantly reduced prevalence of type 2 diabetes mellitus compared with wild type (19 vs 68%, P=0.001) despite the higher levels of both serum morning (21.7±6 vs 27.3±8.6 μg/dl, P=0.009) and midnight cortisol (18.8±5.8 vs 24.0±8.0 μg/dl, P=0.01). The negative association between diabetes and A3669G GR polymorphism remained significant when data were adjusted for potential confounding factors.
Conclusions
The A3669G polymorphism of the GR gene plays a protective role in patients with CS, attenuating the effects of GC excess on glucose metabolism as shown by their reduced risk of diabetes
An experimental study on dependence liability of zipeprol.
No full textZipeprol, a piperazine ethanol derivative, is a non-essential but widely used (paediatric) antitussive, which is not legally considered as being capable of creating dependence or abuse liability. A first group of experimental results was obtained assaying the displacement of 1 nM [3H]naloxone by zipeprol vs morphine on the rat brain homogenate fractions. A second group was carried out on the longitudinal muscle of guinea-pig ileum, using the field stimulation technique, either in the absence or in the presence of naloxone 1 x 10(-5)M or in the absence or in the presence of yohimbine 1 x 10(-5)M. Further investigations concerning the pharmacological and the biochemical characterization of the mechanisms involved in abuse liability were carried out by means of the in vitro inhibition of ACh response on the guinea-pig ileum preparation. The results indicate zipeprol as a moderate opioid agonist, which also shows a direct anticholinergic effect, independent of presynaptic alpha 2 interaction
Fracture risk assessment before and after resolution of endogenous hypercortisolism: Is the FRAX(®) algorithm useful?
No full textPurpose Fracture risk data following curative treatment of Cushing's syndrome (CS) are scarce and the role of bisphosphonates in bone recovery after remission is controversial. We evaluated the effects of hypercortisolism remission in bone recovery in CS. Then, we assessed if the FRAX (R) algorithm calculated before the cure can predict fracture risk after cure.
Methods Thirty-six patients with CS were retrospectively investigated. Bone turnover markers, bone mineral density (BMD) at the lumbar spine (L1-L4) and left femur (both neck and total hip were considered), and fracture risk using FRAX (R) algorithm with femoral neck BMD were evaluated at diagnosis and after a median follow-up of 24 months (range 12-108 months) from hypercortisolism remission. Data about bone active therapy were analyzed.
Results Hypercortisolism remission was associated with the improvement of all densitometric parameters and with the reduction of fracture risk. The percentage change in BMD and the fracture risk were not significantly different in bisphosphonate-treated vs. untreated patients. During follow-up, three fractured patients at baseline exhibited a new vertebral fracture. A baseline 10-year probability of major osteoporotic fractures (FRAX (R) Major) of 17 % was able to predict the occurrence of a new vertebral fracture during follow-up after cure with 100 % sensitivity, 77 % specificity, 81 % positive predictive value and 100 % negative predictive value.
Conclusions Osteoporosis and fracture risk may be reversible after curative treatment of CS, regardless of bisphosphonate therapy. We suggest applying the FRAX (R) algorithm to all active CS patients using a baseline FRAX (R) Major of 17 % as "intervention threshold"
Muscarinic modulation of neurotransmission: the effects of some agonists and antagonists.
No full text
- …
