Morris water maze learning in Long-Evans rats is differentially affected by blockade of D1-like and D2-like dopamine receptors

Dopaminergic neurotransmission is involved in several brain functions including spatial cognition. In the present study we examine the effects of systemic administration of D1-like receptor antagonist SCH23390 and D2-like receptor antagonist sulpiride on the acquisition of the Morris water maze task. We used visible versus hidden platform versions of the MWM in order to distinguish between the effects of the drugs on the procedural versus cognitive aspects of the task. SCH23390 was found to prolong escape latencies to the visible platform at a higher dose (0.05mg/kg), whilst the lower dose (0.02mg/kg) left both procedural and cognitive functions almost unchanged. SCH23390 was also found to reduce swimming speed. Sulpiride did not affect the visible platform learning at any of three doses studied (30, 60 and 100mg/kg); the highest dose of sulpiride (100mg/kg) impaired place navigation to the hidden platform, without affecting the swim speed. The results of the present study show a difference in the involvement of D1-like and D2-like receptors in the MWM acquisition.     

Knowledge of osteoporosis correlated with hormone therapy use and health status

OBJECTIVES: The study objectives were: (a) to evaluate knowledge about osteoporosis and to identify its correlates among women > or =40 years of age attending outpatient centers; (b) to compare the level of knowledge between women already receiving treatment for osteoporosis and first-time attendees. METHODS: A cross-sectional survey was conducted with women recruited from nine outpatient centres in the Czech Republic. The women were divided into two subgroups: patients who have already been diagnosed with osteoporosis (osteopenia) and who are receiving treatment for the disease (OS group); first-time attendees who have been referred for the assessment of osteoporosis (comparison group). The patient's knowledge of osteoporosis was assessed using the Osteoporosis Questionnaire (OPQ) developed by Pande et al. [Pande KC, Takats D, Kanis JA, Edwards V, Slade P, McCloskey EV. Development of a questionnaire (OPQ) to assess patient's knowledge about osteoporosis. Maturitas 2000;37:75-81]. RESULTS: A total of 474 women (median age 63 years) were studied (306 in the OS group, 168 in the comparison group). Knowledge scores based on OPQ (median) were 7 and 6 points in the OS and comparison groups, respectively. When adjusted for age, the statistics showed better knowledge patients in the OS group (P=0.019). In both the OS and comparison groups, knowledge was found to be correlated positively with education (P<0.001) and experience of hormone replacement therapy (HRT) (P<0.001) and negatively with age (P<0.001). Knowledge was higher among women with better health status in the OS group. CONCLUSION: Knowledge about osteoporosis among Czech women aged > or =40 years and attending outpatient centers is relatively poor. To improve it, special attention should be paid to elderly women, those who have not used HRT, poorly educated women and those treated with several drugs.     

Simultaneous Pharmacokinetic Modeling of Gentamicin,Tobramycin and Vancomycin Clearance from Neonates to Adults: Towards a Semi-physiological Function for Maturation in Glomerular Filtration

Purpose

Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs, the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults.

Methods

In the pharmacokinetic analysis (NONMEM VI) based on data of gentamicin, tobramycin and vancomycin collected in 1,760 patients (age 1 day–18 years, bodyweight 415 g–85 kg), a distinction was made between drug-specific and system-specific information. Since the maturational model for clearance is considered to contain system-specific information on the developmental changes in GFR, one GFR maturational function was derived for all three drugs.

Results

Simultaneous analysis of these three drugs showed that maturation of GFR mediated clearance from preterm neonates to adults was best described by a bodyweight-dependent exponent (BDE) function with an exponent varying from 1.4 in neonates to 1.0 in adults (Cl_GFR?=?Cl_drug*(BW/4 kg)^BDE with BDE?=?2.23*BW^?0.065). Population clearance values (Cl_drug) for gentamicin, tobramycin and vancomycin were 0.21, 0.28 and 0.39 L/h for a full term neonate of 4 kg, respectively.

Discussion

Based on an integrated analysis of gentamicin, tobramycin and vancomycin, a semi-physiological function for GFR mediated clearance was derived that can potentially be used to establish evidence based dosing regimens of renally excreted drugs in children.     

Severe hepatic side effects of ezetimibe.

BACKGROUND AND AIMS: Ezetimibe was introduced recently as a new class of cholesterol-lowering drugs. Until now only limited increases of transaminase levels were reported. METHODS: We studied 2 patients with severe hepatic side effects of ezetimibe in a general community hospital. RESULTS: Ezetimibe may lead to 2 distinct types of severe hepatic side effects. CONCLUSIONS: Ezetimibe may rarely cause hepatotoxicity, severe cholestatic hepatitis, or acute autoimmune hepatitis.