Treatment of Paget''s disease of bone with single dose intravenous pamidronate.

OBJECTIVES--To assess the efficacy of a single intravenous infusion of pamidronate in Paget's disease of bone. METHODS--Fourteen patients with active Paget's disease (raised serum alkaline phosphatase, bone pain or neurological involvement) were treated with a single intravenous infusion of 105 mg pamidronate. Patients were assessed for biochemical and clinical improvement for up to two years following treatment. A further infusion was given following symptomatic relapse (pain at a known site of pagetic involvement). RESULTS--Serum alkaline phosphatase fell following treatment, with a nadir 5.9 months after treatment. Bone pain was improved in nine of 12 patients after six months. Retreatment of four patients resulted in a similar response. CONCLUSION--Single dose intravenous pamidronate (105 mg) is a convenient and effective treatment for Paget's disease.     

Non-photoperiodic regulation of reproductive physiology in the flexibly breeding pine siskin (Spinus pinus)

Salivary cortisol has been recently used to assess welfare of captive and free-ranging animals. However, rhythms of cortisol secretion may vary annually and thus, it is necessary to take into account these rhythms when evaluating the physiological significance of fluctuations of this hormone throughout the year as stress indicator in animals. Here, we analyze monthly differences in cortisol secretion in Asian elephants (Elephas maximus) during a year. Saliva samples of eight adult female Asian elephants were collected and analyzed using Radioimmunoassay. Results revealed an overall seasonal pattern of salivary cortisol secretion and significant differences in cortisol concentration among months were found. Overall, the highest cortisol levels were recorded in October, and then decreased until reaching the lowest concentration in April. However, some individual variations were found respect this annual overall trend. The occurrence of this annual pattern of cortisol secretion should be taken into account when using cortisol as a tool to assess animal welfare in captive animal at zoological parks, as well as it opens new questions to further analyze this pattern and its variations, as well as the endogenous mechanisms controlling it.     

Prevalence and predictors of abnormal arterial function in statin-treated type 2 diabetes mellitus patients

Arterial dysfunction (AD) in type 2 diabetes mellitus (T2DM) predicts cardiovascular events. The objective was to investigate the prevalence and predictors of AD in statin-treated T2DM patients. We measured flow-mediated (FMD) and nitrate-mediated (NMD) brachial artery dilatation in 86 statin-treated T2DM patients. Patients were classified into 2 groups: normal arterial function (FMD ≥3.7% with NMD ≥11.9%) or AD (FMD <3.7% with or without NMD <11.9%). Endothelial dysfunction without smooth muscle cell dysfunction (ED) was defined as FMD less than 3.7% with NMD of at least 11.9%, and endothelial dysfunction with smooth muscle cell dysfunction (ED/SMD) was defined as FMD less than 3.7% with NMD less than 11.9%. Predictors of arterial function were investigated using linear and logistic regression methods. The prevalence of AD was 33.7% (23.2% with ED and 10.5% with ED/SMD). In multivariate linear regression, history of hypertension (P < .01), statin dose (P < .05), and estimated glomerular filtration rate (eGFR) (P = .02) were significant predictors of FMD. Sex (P < .01) and creatinine (P = .03) or eGFR (P = .02) predicted NMD. In multivariate logistic regression, the independent predictors of AD were history of hypertension (odds ratio [OR], 8.79; 95% confidence interval, 2.14-36.12; P < .01), age (OR, 1.08; 1.01-1.17; P = .03), and statin dose (OR, 0.33; 0.12-0.87; P = .02). A history of hypertension (OR, 8.99; 1.87-43.26; P < .01) was the sole independent predictor of ED; eGFR (OR, 0.01; 0.00-0.26; P < .01) independently predicted ED/SMD. Our data suggest that one third of statin-treated diabetic patients have residual AD, mainly due to ED alone. Earlier identification and treatment of hypertension and renal impairment may improve AD and further decrease cardiovascular risk in such patients.     

Postprandial lipoprotein metabolism in familial hypercholesterolemia: thinking outside the box

Familial hypercholesterolemia (FH) is a dominantly inherited disorder principally due to mutations in the low-density lipoprotein (LDL) receptor that classically cause markedly elevated plasma LDL cholesterol concentrations and premature coronary heart disease (CHD). However, elevated plasma LDL cholesterol alone does not fully account for the increase or variation in risk of CHD. We propose a hypothetical model for the role of postprandial dyslipoproteinemia based on the overproduction and decreased catabolism of triglyceride-rich lipoproteins, which may be a consequence of LDL receptor deficiency. Expression of postprandial dyslipoproteinemia in FH may also depend on the type of pathogenic gene variants and on coexistent conditions, particularly obesity and insulin resistance. Further research is required to investigate our model proposed and to test whether treating postprandial dyslipoproteinemia decreases CHD risk in FH incremental to standard therapy.     

Cooperation and assortativity with dynamic partner updating

The natural tendency for humans to make and break relationships is thought to facilitate the emergence of cooperation. In particular, allowing conditional cooperators to choose with whom they interact is believed to reinforce the rewards accruing to mutual cooperation while simultaneously excluding defectors. Here we report on a series of human subjects experiments in which groups of 24 participants played an iterated prisoner's dilemma game where, critically, they were also allowed to propose and delete links to players of their own choosing at some variable rate. Over a wide variety of parameter settings and initial conditions, we found that dynamic partner updating significantly increased the level of cooperation, the average payoffs to players, and the assortativity between cooperators. Even relatively slow update rates were sufficient to produce large effects, while subsequent increases to the update rate had progressively smaller, but still positive, effects. For standard prisoner's dilemma payoffs, we also found that assortativity resulted predominantly from cooperators avoiding defectors, not by severing ties with defecting partners, and that cooperation correspondingly suffered. Finally, by modifying the payoffs to satisfy two novel conditions, we found that cooperators did punish defectors by severing ties, leading to higher levels of cooperation that persisted for longer.     

One-Month Serotonin Infusion Results in a Prolonged Fall in Blood Pressure in the Deoxycorticosterone Acetate (DOCA) Salt Hypertensive Rat

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