Metal Ionophore Treatment Restores Dendritic Spine Density and Synaptic Protein Levels in a Mouse Model of Alzheimer's Disease

We have previously demonstrated that brief treatment of APP transgenic mice with metal ionophores (PBT2, Prana Biotechnology) rapidly and markedly improves learning and memory. To understand the potential mechanisms of action underlying this phenomenon we examined hippocampal dendritic spine density, and the levels of key proteins involved in learning and memory, in young (4 months) and old (14 months) female Tg2576 mice following brief (11 days) oral treatment with PBT2 (30 mg/kg/d). Transgenic mice exhibited deficits in spine density compared to littermate controls that were significantly rescued by PBT2 treatment in both the young (+17%, p<0.001) and old (+32%, p<0.001) animals. There was no effect of PBT2 on spine density in the control animals. In the transgenic animals, PBT2 treatment also resulted in significant increases in brain levels of CamKII (+57%, p = 0.005), spinophilin (+37%, p = 0.04), NMDAR1A (+126%, p = 0.02), NMDAR2A (+70%, p = 0.05), pro-BDNF (+19%, p = 0.02) and BDNF (+19%, p = 0.04). While PBT2-treatment did not significantly alter neurite-length in vivo, it did increase neurite outgrowth (+200%, p = 0.006) in cultured cells, and this was abolished by co-incubation with the transition metal chelator, diamsar. These data suggest that PBT2 may affect multiple aspects of snaptic health/efficacy. In Alzheimer's disease therefore, PBT2 may restore the uptake of physiological metal ions trapped within extracellular β-amyloid aggregates that then induce biochemical and anatomical changes to improve cognitive function

Volume CXIV, Number 4, November 7, 1996

Objective: Turner syndrome (TS) is a chromosomal disorder caused by complete or partial X chromosome monosomy that manifests various clinical features depending on the karyotype and on the genetic background of affected girls. This study aimed to systematically investigate the key clinical features of TS in relationship to karyotype in a large pediatric Turkish patient population.Methods: Our retrospective study included 842 karyotype-proven TS patients aged 0-18 years who were evaluated in 35 different centers in Turkey in the years 2013-2014.Results: The most common karyotype was 45,X (50.7%), followed by 45,X/46,XX (10.8%), 46,X,i(Xq) (10.1%) and 45,X/46,X,i(Xq) (9.5%). Mean age at diagnosis was 10.2±4.4 years. The most common presenting complaints were short stature and delayed puberty. Among patients diagnosed before age one year, the ratio of karyotype 45,X was significantly higher than that of other karyotype groups. Cardiac defects (bicuspid aortic valve, coarctation of the aorta and aortic stenosis) were the most common congenital anomalies, occurring in 25% of the TS cases. This was followed by urinary system anomalies (horseshoe kidney, double collector duct system and renal rotation) detected in 16.3%. Hashimoto's thyroiditis was found in 11.1% of patients, gastrointestinal abnormalities in 8.9%, ear nose and throat problems in 22.6%, dermatologic problems in 21.8% and osteoporosis in 15.3%. Learning difficulties and/or psychosocial problems were encountered in 39.1%. Insulin resistance and impaired fasting glucose were detected in 3.4% and 2.2%, respectively. Dyslipidemia prevalence was 11.4%.Conclusion: This comprehensive study systematically evaluated the largest group of karyotype-proven TS girls to date. The karyotype distribution, congenital anomaly and comorbidity profile closely parallel that from other countries and support the need for close medical surveillance of these complex patients throughout their lifespa

Reduction in tumour cell invasion by pigment epithelium-derived factor is mediated by membrane type-1 matrix metalloproteinase downregulation

Prostate cancer and breast cancer are major killers among males and females respectively. In this study, pigment epithelium-derived factor (PEDF) was examined for its effect on commonly used human prostate cancer and human breast cancer cell lines. PEDF increased adhesion of cells to collagen-I, with decreased expression of phosphorylated focal adhesion kinase (p-Fak) consistent between the two cell types. Invasion of both tumour cell types through collagen-I was also reduced by PEDF, with decreased expression of membrane type-1 matrix metalloproteinase (MT1-MMP). These results were confirmed with specific antibodies to MT-MMP1. This study provides some vital clues as to which molecular players are perturbed by PEDF treatment of human prostate and breast cancer cells, raising hope that PEDF can in future be trialled against these major cancers in attempts to procure safer yet effective therapies for cancer

Preparation and Physicochemical Characterizations of Solid Lipid Nanoparticles Containing Dotap for Dna Delivery

The aim of this study was to prepare and evaluate stable cationic solid lipid nanoparticles (SLNs) as colloidal carriers for gene therapy. SLNs were mainly composed of three different biocompatible and biodegradable matrix lipids called tripalmitin, glyceryl dibehenate, and triglyceride, all containing the cationic lipid N-(1-(2,3-dioleoyloxy)propy1)-N, N, N-trimethylammonium (DOTAP (R)). Each of these SLNs were divided into three parts and characterized by applying different processes: Part I was autoclaved (121 degrees C, 15 min), Part II was lyophilized (5 mbar, 50 degrees C), and Part III was kept in its intact form. These parts were stored at 4 degrees C, 25 degrees C (room temp.), and 40 degrees C for short-term stability tests. The formulations were tested physically regarding the particle size and zeta potential. pUC18 plasmid DNA was used as the genetic material. Zeta potentials of all SLNs and pDNA-SLN complexes were determined to be highly positive (between +28.90 and +59.39). Crystallization processes of lipid matrices were characterized by X-ray diffractometry and differential scanning calorimetry. pDNA binding ability of SLNs and the stability of pDNA-SLN complexes with DNase I enzyme were also determined by gel electrophoresis. It was determined that all formulations became positively charged with DOTAP (R). They were able to bind DNA and were partially protective against enzyme degradation. Although additional studies are necessary, this study reveals the promising potential of this gene delivery system for gene therapy.WoSScopu

Prevalence of pneumatization of the articular eminence and glenoid fossa viewed on cone-beam computed tomography examinations in a Turkish sample

Objective The aim of this study is to evaluate the prevalence of the pneumatization of the articular eminence and glenoid fossa (PAT and PGF, respectively) using cone-beam computed tomography (CBCT). Methods CBCT images of 1000 patients (511 females and 489 males) representing 2000 regions of interest (the glenoid fossa and articular eminence of each patient) were examined retrospectively with regard to age, gender, laterality, and type of pneumatization. The mean age of the female patients was 39.66 and that of males was 39.79. Suitable images from patients aged 16 years and over found in the archives of CBCT images were included in the study. The data were assessed using IBM SPSS 20 and statistical comparisons between two categorical variables were conducted using Chi square tests. Results It was observed that 14.7% of the patients had PAT and 47.1% had PGF. There was no significant difference in PAT and PGF prevalence between ages, age ranges, and gender in our study (p > 0.5). Conclusions It is important to evaluate the pneumatic cells in the articular eminence and glenoid fossa regions before surgery. It was also found that CBCT is more helpful in detecting pneumatization than plain film

Preparation and characterization of sulfonyl-hydrazine attached poly(styrene-divinylbenzene) beads for separation of albumin

WOS: 000244617500008Novel sulfonyl-hydrazine carrying poly(styrene-divinylbenzene), poly(S-DVB)-S-NH2 ion-exchange beads (size between 210 and 425 mu m) were prepared via suspension polymerization and, were first used as an ion-exchange support for adsorption of human serum albumin (HSA) from aqueous solution. The influence of pH, equilibrium time, ionic strength and initial albumin concentration on the adsorption capacity of the poly(SDVB)-S-NH2 ion-exchange beads has been investigated in a batch system and the unmodified poly(S-DVB) beads were used as control system. Maximum HSA adsorption onto poly(S-DVB)-S-NH2 ion-exchange beads was found to be 63.05 mg/g at pH 7.0. The experimental equilibrium data for HSA adsorption onto poly(S-DVB)-S-NH2 beads was well described by the Langmuir isotherm model. Kinetic parameters of this adsorption system were also analyzed for HSA adsorption onto beads and, the first-order rate equations were favorable. Finally, the poly(S-DVB)-S-NH2 beads was used for the purification of HSA from whole human serum and, the purity of the eluted HSA from the beads was determined as 89% by HPLC from single step purification protocol. (c) 2006 Elsevier B.V. All rights reserved

Effect of lairage time after short distance transport on some biochemical stress parameters and meat quality of Karayaka lambs

Sheep are transported for various causes such as sale, breeding and slaughter. Several potential stressors which impair the meat quality affect sheep during the transport. Lairage is a common commercial practise to get rid of transportation stress before slaughter

Effects of Stocking Density of Lambs on Biochemical Stress Parameters and Meat Quality Related to Commercial Transportation

The aim of this study was to evaluate the effects of stocking density (0.20 and 0.27 m(2)/lamb) during transportation on certain biochemical stress parameters and meat quality characteristics of fifty-five Karayaka lambs divided into two groups. The front compartment of the trailer was loaded at high stocking density (HD: 0.20 m(2)/lamb; n=33) and the remainder was loaded at low stocking density (LD: 0.27 m(2)/lamb; n=22). The distance was approximately 130 km and duration was 2 h 15 min. Blood samples were taken just before and just after transportation. Glucose (P0.05). Transportation with a stocking density of 0.20 m(2)/lamb resulted in higher stress responses in lambs compared with a stocking density of 0.27 m(2)/lamb. However, increased stress in the HD group did not lead to any adverse effects on meat quality characteristics. In the determination of stocking density, a compromise that gives animal welfare and commercial objectives equal status would improve the current situation

EFFECTS OF STOCKING DENSITY OF LAMBS ON BIOCHEMICAL STRESS PARAMETERS AND MEAT QUALITY RELATED TO COMMERCIAL TRANSPORTATION

The aim of this study was to evaluate the effects of stocking density (0.20 and 0.27 m(2)/lamb) during transportation on certain biochemical stress parameters and meat quality characteristics of fifty-five Karayaka lambs divided into two groups. The front compartment of the trailer was loaded at high stocking density (HD: 0.20 m(2)/lamb; n=33) and the remainder was loaded at low stocking density (LD: 0.27 m(2)/lamb; n=22). The distance was approximately 130 km and duration was 2 h 15 min. Blood samples were taken just before and just after transportation. Glucose (P0.05). Transportation with a stocking density of 0.20 m(2)/lamb resulted in higher stress responses in lambs compared with a stocking density of 0.27 m(2)/lamb. However, increased stress in the HD group did not lead to any adverse effects on meat quality characteristics. In the determination of stocking density, a compromise that gives animal welfare and commercial objectives equal status would improve the current situation