Electrophysiological and behavioral responses to ketamine in mice with reduced Akt1 expression

Rationale

A number of studies have associated reduced Akt1 expression with vulnerability for schizophrenia. Although mice with deletion of a single copy of the Akt1 gene (Akt1^+/?) show reduced Akt1 expression relative to wild-type (WT) animals, the extent to which these mice show schizophrenia-like phenotypic changes and/or increased susceptibility to epigenetic or non-genetic factors related to schizophrenia is unknown.

Objectives

Mutant mice were assessed on electroencephalographic/event-related potential (EEG/ERP) and behavioral (acoustic startle and pre-pulse inhibition) measures relevant to schizophrenia. Mice were also assessed following exposure to the NMDA receptor antagonist ketamine, a potent psychotomimetic drug, in order to assess the role of reduced Akt1 expression as a vulnerability factor for schizophrenia. Methods Akt1^+/?, Akt1^?/?, and WT mice received a series of paired-click, white noise stimuli, following ketamine (50 mg/kg) and saline injections. EEG was analyzed for ERPs and event-related power. Akt1^+/? and WT mice were also assessed on PPI following ketamine (50 mg/kg) or saline injection.

Results

Akt1^+/? and Akt1^?/? mice displayed reduced amplitude of the P20 component of the ERP to the first click of a paired-click stimulus, as well as reduced S1–S2 difference for P20 and N40 components, following ketamine. Mutant mice also showed increased reduction in gamma synchrony and theta suppression following ketamine. Akt1^+/? mice displayed reduced pre-pulse inhibition.

Conclusions

Reduced genetic expression of Akt1 facilitated ketamine-induced changes of EEG and behavior in mice, suggesting that reduced Akt1 expression can serve as a vulnerability factor for schizophrenia.     

Stability of Y-splitting procedure combined with hang-back recession of the rectus muscle in rabbit eyes

Background

The Y-splitting procedure has been used both to treat up-shoots and down-shoots in Duane syndrome, and as a substitute for posterior fixation suture. The Y-split is often performed in conjunction with a hang-back recession when a large amount of recession or an adjustable suture is necessary. Herein, we evaluated the stability of Y-splitting hang-back recession in the rectus muscle.

Methods

Under general anesthesia, a 5-mm hang-back recession of the superior rectus muscle (SR) with Y-splitting was performed in ten eyes from ten rabbits (hang-back group). A conventional recession was performed in the SR of the fellow eye (control group). Six weeks after the procedure, the distance between the original insertion and the recessed SR (recession amount) and the width between the nasal and temporal halves of the SR were measured. These values were compared to the measurements taken at the time of surgery.

Results

The hang-back group had a significantly larger forward displacement than the control group (P?<?0.001 for both the nasal and temporal halves). The width change between the nasal and temporal halves was also significantly larger in the hang-back group (4.94?±?1.32 mm) than in the control group (1.14?±?0.60 mm, P?<?0.001). Additionally, the Y-configuration appeared to be more collapsed in the hang-back group than in the control group.

Conclusion

Y-splitting of the rectus muscle may be unstable when it is combined with a hang-back recession. Surgeons should consider this possibility when performing Y-splitting procedures.     

Enhancement of cellular binding efficiency and cytotoxicity using polyethylene glycol base triblock copolymeric nanoparticles for targeted drug delivery

Folate (FA) conjugated tri-block copolymers were prepared by bioconjugation of poly epsilon-caprolactonediol and various molecular weights of diamine polyethylene glycol. The synthetic tri-block copolymers were characterized by 1H-NMR. Three types of nanoparticles were prepared by nanoprecipitation. Their size and morphology were verified by laser scattering and transmission electron microscopy, respectively. The colloidal stability of the nanoparticles was evaluated by turbidity test. The anticancer drug doxorubicin (DOX) was encapsulated in the nanoparticles during preparation. Drug loading amounts and release behavior from prepared nanoparticles were investigated. Fluorescent-activated cell sorting analysis and epi-fluorescencic microscopic imaging of prepared nanoparticles exhibited good cellular uptake against target cells. FA receptor expressed OVCAR3 cells that showed higher mean fluorescence intensity than FA receptor defect A549 cells at specific polyethylene glycol chain lengths. The cell cytotoxicity of prepared nanoparticles was evaluated for receptor mediated drug delivery.     

Calcifications in prostate and ejaculatory system: a study on 298 consecutive whole mount sections of prostate from radical prostatectomy or cystoprostatectomy specimens

Although calcifications in the prostate are a common manifestation, the relationship between calcifications and prostate cancer is not clearly documented as in breast cancer. In addition, anatomical distribution of calcifications by zones of the prostate and ejaculatory system has not been systematically studied. To study the frequency and patterns of calcifications within the prostate and ejaculatory system, we reviewed the whole mount sections of 298 consecutive prostatectomy or cystoprostatectomy specimens. Calcifications were evaluated in the prostate (central, peripheral and transition zones, and verumontanum), ejaculatory ducts, and seminal vesicles. We graded the degree of calcifications as mild, moderate, or severe. Calcifications in the prostate and ejaculatory system were common, and their frequency in our series is as follows: 88.6% (264/298) of prostates, 58.1% (173/298) of seminal vesicles, and 17.1% (51/298) of ejaculatory ducts. The prostatic calcifications occurred mostly in benign glands and/or stroma of all zones and the verumontanum. Calcifications were more common in the transition zone than other zones. There were 4 cases of prostatic calcifications in the areas of prostatic adenocarcinoma: 3 cases with calcifications in the tumor glands and 1 case with calcifications in tumor stroma but not in the accompanying tumor glands. In conclusion, calcifications are a very common finding in prostatectomy specimens and seem mostly to be associated with benign prostatic hyperplasia. However, calcifications can occur in direct association with prostatic adenocarcinoma, although the incidence of this association is not as high as in breast carcinoma. Also, ejaculatory system calcifications are not an infrequent finding.     

Serum anti-Müllerian hormone and inhibin B levels at ovulation triggering day can predict the number of immature oocytes retrieved in in vitro fertilization cycles

The aim of this study was to investigate whether serum levels of anti-Müllerian hormone (AMH) and inhibin B at ovulation triggering day correlate with the number of immature oocytes obtained from stimulated in vitro fertilization (IVF) cycles. Fifty-nine consecutive cycles of ovarian hyperstimulation and IVF were selected from 45 women who had tubal (n=18) or unexplained infertility (n=27) and obtained at least one oocyte. Serum levels of AMH and inhibin B at ovulation triggering day were measured by enzyme-linked immunosorbent assay (ELISA). Univariate analysis and multiple regressions revealed that serum AMH or inhibin B levels were significantly correlated with immature oocyte count and the correlation coefficients were higher compared to the mature oocyte count. Serum AMH and inhibin B levels on triggering day seems to be more closely related with the immature oocyte count and thus could be good predictors to determine the immature oocyte count in IVF cycle.     

Association of UCP1 genetic polymorphisms with blood pressure among Korean female subjects

Recent studies have provided some clues with regard to the relationship existing between uncoupling protein 1 (UCP1) and blood pressure in animal experiments. In an attempt to determine the genetic polymorphisms that are associated with blood pressure in humans, we have analyzed genetic polymorphisms in UCP1 gene. In this study, we assessed the association between UCP1 genotypes and systolic blood pressure (SBP) and diastolic blood pressure (DBP), in a population comprised of 832 Korean female subjects, using a general linear model, which was adjusted for age and body mass index (BMI). Among 4 genetic polymorphisms and the haplotypes constructed from them, haplotype3 of UCP1, UCP1-ht3[GAGA], evidenced significant associations with SBP (p=0.005) and DBP (p=0.013). However, this haplotype was not significantly associated with obesity phenotypes, including BMI or fat mass (p>0.05), thereby suggesting that its association with blood pressure was independent of obesity phenotypes.     

Cognitions and Insomnia Subgroups

This study explored cognitive predictors of multiple symptoms of insomnia (difficulty with sleep initiation, maintenance, and early morning awakenings) among a sample of individuals seeking cognitive-behavior therapy for insomnia. Participants consisted of 146 clinical patients with insomnia of which 67 (45.89%) were classified as Single Symptoms subgroup and 79 (54.11%) as Combined subgroup. A receiver operating curve (ROC) analysis was conducted to identify predictors of Combined versus Single Symptom subgroups. The set of predictor variables included demographics, sleep-related cognitions, circadian preferences, depression symptoms, and self-report sleep parameters with insomnia subgroups (Combined versus Single Symptom only) as the dependent variable. The ROC analysis identified two significant predictors: Self Efficacy Scale (SES) <23 and a 3-item subscale of the Glasgow Content of Thoughts Inventory (GCTI) assessing “thoughts about the environment” with scores ≥5. Post-hoc comparisons revealed that individuals with combined symptoms who had SES score <23 had significantly longer sleep onset latency (SOL) and more number of nights with SOL >30 min, poorer sleep quality, higher insomnia severity, less morningness tendency, higher depression symptom severity, and more anxiety about anxiety and about sleep compared to individuals with SES score ≥23. These findings indicate that low self-efficacy and increased thoughts about the environment are associated with having multiple symptoms of insomnia. Further research should examine the specific role of self-efficacy and thought content in the etiology of individuals who suffer from multiple symptoms of insomnia.     

Age- and gender-related differences in circulating natural killer T cells and their subset levels in healthy Korean adults

Natural killer T (NKT) cells have been reported to play crucial roles in a variety of diseases, including infectious diseases, autoimmunity, and cancers. Previous studies have reported wide age- and/or sex-related variations in circulating NKT cell levels in healthy subjects, but reported results are discrepant. In this study, the authors examined NKT cell levels in the peripheral blood of healthy Korean subjects and investigated potential relationships between clinical parameters and NKT cells and their subset levels. One hundred and thirty-eight age- and sex-matched healthy subjects were enrolled in this study. NKT cell and NKT subset levels were measured by flow cytometry. Circulating NKT cell levels were found to vary widely (0.01-5.15%) in the study subjects and to be lower in men than in women (P<0.05). Notably, gender-related differences in NKT cell levels were more prominent in elderly subjects (P<0.05). Furthermore, alterations in NKT subset compositions were found in elderly men, in whom the proportion of CD4+ NKT cells was elevated and that of double-negative NKT cells was reduced. Our data suggest that circulating NKT cells and NKT subset levels are affected by age and gender in the Korean population.