<Emphasis Type="Italic">Fgf9</Emphasis><Superscript><Emphasis Type="Italic">Y162C</Emphasis></Superscript> Mutation Alters Information Processing and Social Memory in Mice

In neuropsychiatric diseases, such as major depression and anxiety, pathogenic vulnerability is partially dictated by a genetic predisposition. The search continues to define this genetic susceptibility and establish new genetic elements as potential therapeutic targets. The fibroblast growth factors (FGFs) could be interesting in this regard. This family of signaling molecules plays important roles in development while also functioning within the adult. This includes effects on aspects of brain function such as neurogenesis and synapse formation. Of this family, Fgf9 is expressed in the adult brain, but its functional role is less well defined. In this study, we examined the role of Fgf9 in different brain functions by analyzing the behavior of Fgf9 ^Y162C mutant mice, an Fgf9 allele without the confounding systemic effects of other Fgf9 genetic models. Here, we show that this mutation caused altered locomotor and exploratory reactivity to novel, mildly stressful environments. In addition, mutants showed heightened acoustic startle reactivity as well as impaired social discrimination memory. Notably, there was a substantial decrease in the level of adult olfactory bulb neurogenesis with no difference in hippocampal neurogenesis. Collectively, our findings indicate a role for the Fgf9 ^Y162C mutation in information processing and perception of aversive situations as well as in social memory. Thus, genetic alterations in Fgf9 could increase vulnerability to developing neuropsychiatric disease, and we propose the Fgf9 ^Y162C mutant mice as a valuable tool to study the predictive etiological aspects.     

MORNING-EVENING ADMINISTRATION TIME DIFFERENCES IN DIGOXIN KINETICS IN HEALTHY YOUNG SUBJECTS

Digoxin, frequently used in the treatment of congestive heart failure, has a very narrow therapeutic index. We studied the differences in digoxin pharmacokinetics when ingested in the morning versus evening. A single digoxin (0.25 mg) dose was given orally to the same group of 10 diurnally active healthy (6 male and 4 female) volunteers in the morning at 08:00 and evening at 20:00 in separate experiments scheduled 2 weeks apart. Blood samples were collected at specific times for 48h after each timed dose; digoxin was determined by radioimmunoassay (RIA). Maximum plasma concentration C_max; T_max, the time to reach C_max; area under plasma concentration curve AUC; and elimination half-time T_1/2 of digoxin were determined. T_max was statistically significantly shorter (54 min) following 08:00 dosing compared to 20:00 dosing (96 min). Although the C_max was higher after morning than evening dosing, it was not significantly so. No other parameter of digoxin pharmacokinetics except T_max exhibited administration time dependency. (Chronobiology International, 18(5), 841-849, 2001)     

Thyroid Functions and Trace Elements in Pediatric Patients with Exogenous Obesity

Obesity is a multifactorial disease developing following impairment of the energy balance. The endocrine system is known to be affected by the condition. Serum thyroid hormones and trace element levels have been shown to be affected in obese children. Changes in serum thyroid hormones may result from alterations occurring in serum trace element levels. The aim of this study was to evaluate whether or not changes in serum thyroid hormone levels in children with exogenous obesity are associated with changes in trace element levels. Eighty-five children diagnosed with exogenous obesity constituted the study group, and 24 age- and sex-matched healthy children made up the control group. Serum thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), thyroglobulin (TG), selenium (Se), zinc (Zn), copper (Cu), and manganese (Mn) levels in the study group were measured before and at the third and sixth months of treatment, and once only in the control group. Pretreatment fT4 levels in the study group rose significantly by the sixth month (p?=?0.006). Zn levels in the patient group were significantly low compared to the control group (p?=?0.009). Mn and Se levels in the obese children before and at the third and sixth months of treatment were significantly higher than those of the control group (p?=?0.001, p?=?0.001). In conclusion, fT4, Zn, Cu, Mn, and Se levels are significantly affected in children diagnosed with exogenous obesity. The change in serum fT4 levels is not associated with changes in trace element concentrations.     

Biochemical and Molecular Characterization of Some Centaurea Species Growing in the Eastern Anatolia Region of Turkey

Random amplified polymorphic DNA (RAPD) and fatty acid (FAME) profiles were used to examine phenotypic and genetic relationships among 16 Centaurea species growing wild in the eastern Anatolia region of Turkey. Thirteen decamer primers were used to examine polymorphism. According to the RAPD results, 99 amplicons in the size range of 50–1000 bp were produced from 13 primers in 16 Centaurea species. Genetically four distinct groups were determined among the species of Centaurea, which represents high genetic variation. In the 16 species, 14 fatty acids were determined according to FAME results. Both FAME and RAPD results showed that C. virgata is genetically different from other species. The differences in the composition of fatty acids among Centaurea species suggest that fatty acid profiles could be used to differentiate among some of these species. Results of this study show that RAPD and FAME analyses are consistent.     

The Evaluation of the Oxidative Stress Parameters in Nondiabetic and Diabetic Senile Cataract Patients

The aim of the present study was to evaluate the copper (Cu), zinc (Zn), malondialdehyde (MDA), glutathione (GSH), and advanced oxidation protein products (AOPP) levels and superoxide dismutase (SOD) activities in diabetic senile cataract. Ten patients with diabetic senile cataract and ten patients with nondiabetic senile cataract (control group) were included in this study. AOPP, MDA, and GSH levels and SOD activity were measured by a spectrophotometric method. Serum, lens Cu, and Zn levels were measured by an atomic absorption spectrophotometric method. Both the lens and serum Zn and Cu levels between the two groups were not significantly different (p > 0.05). GSH, AOPP, and MDA levels and the SOD activities in the diabetic senile cataract group were significantly increased as compared to the control group (p < 0.05). Oxidative stress is one of the major factors which may lead to the early cataract formation. Oxidative events are of great importance in diabetic complications and, particularly in the lens, may have a role in the pathogenesis of cataract associated with diabetes mellitus as exhibited in this study.     

Assaying Locomotor Activity to Study Circadian Rhythms and Sleep Parameters in Drosophila

Most life forms exhibit daily rhythms in cellular, physiological and behavioral phenomena that are driven by endogenous circadian (≡24 hr) pacemakers or clocks. Malfunctions in the human circadian system are associated with numerous diseases or disorders. Much progress towards our understanding of the mechanisms underlying circadian rhythms has emerged from genetic screens whereby an easily measured behavioral rhythm is used as a read-out of clock function. Studies using Drosophila have made seminal contributions to our understanding of the cellular and biochemical bases underlying circadian rhythms. The standard circadian behavioral read-out measured in Drosophila is locomotor activity. In general, the monitoring system involves specially designed devices that can measure the locomotor movement of Drosophila. These devices are housed in environmentally controlled incubators located in a darkroom and are based on using the interruption of a beam of infrared light to record the locomotor activity of individual flies contained inside small tubes. When measured over many days, Drosophila exhibit daily cycles of activity and inactivity, a behavioral rhythm that is governed by the animal''s endogenous circadian system. The overall procedure has been simplified with the advent of commercially available locomotor activity monitoring devices and the development of software programs for data analysis. We use the system from Trikinetics Inc., which is the procedure described here and is currently the most popular system used worldwide. More recently, the same monitoring devices have been used to study sleep behavior in Drosophila. Because the daily wake-sleep cycles of many flies can be measured simultaneously and only 1 to 2 weeks worth of continuous locomotor activity data is usually sufficient, this system is ideal for large-scale screens to identify Drosophila manifesting altered circadian or sleep properties.     

Amphenicol and macrolide derived antibiotics inhibit paraoxonase enzyme activity in human serum and human hepatoma cells (HepG2) in vitro

Human serum paraoxonase (hPON1) was separately purified by ammonium sulfate precipitation and hydrophobic interaction chromatography. The in vitro effects of commonly used antibiotics, namely clarithromycin and chloramphenicol, on purified human serum paraoxonase enzyme activity (serum hPON1) and human hepatoma (HepG2) cell paraoxonase enzyme activity (liver hPON1) were determined. Serum hPON1 and liver hPON1 were determined using paraoxon as a substrate and IC(50) values of these drugs exhibiting inhibition effects were found from graphs of hydratase activity (%) by plotting concentration of the drugs. We determined that chloramphenicol and clarithromycin were effective inhibitors of serum hPON1.