Antipsychotics alter the protein expression levels of beta-catenin and GSK-3 in the rat medial prefrontal cortex and striatum.

BACKGROUND: It has been demonstrated that schizophrenics have altered levels and/or phosphorylation states of several Wnt related proteins in the brain, including beta-catenin and GSK-3, and may represent susceptibility loci for schizophrenia. The current study was conducted to assess the effects of antipsychotics on beta-catenin and glycogen synthase kinase-3. METHODS: Western blotting and immunocytochemistry were employed to investigate the effects of antipsychotics on beta-catenin and glycogen synthase kinase-3 following acute, subchronic and chronic drug administration. Specificity of the response was tested using additional drugs such as fluoxetine, amphetamine and valproic acid. RESULTS: Significant increases in the levels of beta-catenin and glycogen synthase kinase-3 total protein were identified following administration of clozapine, haloperidol or risperidone. The phosphorylation state of GSK-3 was also increased but phosphorylated beta-catenin levels were unaffected. Other drug compounds, with the exception of raclopride, had no effect on either GSK-3 or beta-catenin protein levels or distribution. CONCLUSIONS: Targeting of beta-catenin and GSK-3 is a common feature of antipsychotics regardless of class and appears to be mediated by D(2) dopamine receptors. Therefore changes in beta-catenin and GSK-3 may represent one of the mechanisms through which antipsychotics are able to exert behavioral changes.     

Butyrylcholinesterase K variants increase the risk of coronary artery disease in the population of western Iran

The conflicting results of several studies suggest that there is an association between the butyrylcholinesterase-K variant (BCHE-K, G1615A/Ala539Thr) and the risk of developing coronary artery disease (CAD) in diabetes and non-diabetic subjects. The objective of this study was to determine whether the presence of the BCHE-K variant exacerbates the risk of CAD in patients from western Iran with and without type 2 diabetes mellitus (T2DM). This case-control study comprised 464 subjects undergoing their first coronary angiography. They were matched and randomly assigned into four groups: CAD+T2DM+ (CAD/T2DM), CAD+DM(-) (CAD/ND), CAD(-)DM+ (T2DM/NCAD) and CAD(-)DM(-)(control). The BCHE-K variant was detected by PCR-RFLP. The BCHE-K allele frequency in CAD patients with and without T2DM [total CAD (TCAD)] and separately for each group (CAD/T2DM and CAD/ND) was significantly higher than in the control group (21.1 % versus 13.3 % (p = 0.001), 22.4 % versus 13.3 % (p = 0.001) and 19.7 % versus 13.3 % (p = 0.015), respectively). The odds ratios (ORs) for the BCHE-K heterozygous and homozygous variants in TCAD subjects were 1.65 (95 % CI 1.17-2.3; p = 0.004) and 4.3 (1.05-19.4; p = 0.048); for CAD/T2DM individuals 1.76 (1.2-2.6; p = 0.004) and 4.73 (0.96-23.3; p = 0.052); and for CAD/ND patients 1.53 (1.05-2.3; p = 0.029) and 3.88 (0.8-19.7; p = 0.7), respectively. The OR of the BCHE-K allele was found to be 1.74 (1.1-2.4; p = 0.001) in TCAD subjects, 1.87 (1.12-1.48; p = 0.001) in the CAD/T2DM group and 1.59 (1.04-1.4; p = 0.016) in CAD/ND subjects. These data suggest that the BCHE-K allele increases the risk of CAD in the population (with and without DM) in western parts of Iran, and its presence intensifies the risk of CAD in T2DM. The fact that the BCHE-K allele, even in the heterozygous form, exacerbates the risk of CAD in this population, suggests that a specific therapeutic intervention should be considered for this particular group of patients.     

Relationship between advanced glycation end products and increased lipid peroxidation in semen of diabetic men

Aims

Majority of diabetic male patients have disturbances in their reproductive systems. However, the mechanisms underlying these disturbances are largely unknown. Since advanced glycation end products (AGE) have a key role in oxidative stress and cell damage in diabetic complications, we hypothesize that AGEs may be involved sperm lipid peroxidation.

Methods

Total AGEs in seminal plasma of 32 diabetic and 35 non-diabetic men was determined by spectrofluorimetric method and carboxy methyl lysine (CML) level was assayed using ELISA. Contents of lipid peroxidation in sperm and seminal plasma were determined by thiobarbituric acid reaction. Total antioxidant capacity (TAC) was measured by a colorimetric assay.

Results

Total AGEs were found significantly higher in seminal plasma of diabetic men than non-diabetic group (p < 0.001) whereas no significant differences in seminal plasma CML values between two groups was observed. Moreover, sperm and seminal plasma lipid peroxidation were significantly higher in diabetic subjects than non-diabetic men and a significantly lower TAC was detected in diabetic group compare to non-diabetics.

Conclusions

These results showed an increment in AGEs in seminal plasma of diabetic subjects and may suggest a key role for glycation process and increased oxidative stress in reproductive system dysfunction.     

Monitoring Organophosphorous Pesticides Residues in the Shahid Rajaei Dam Reservoir,Sari, Iran

Levels of eight different types of organophosphorous pesticides in water samples from different parts of the Shahid Rajaei dam reservoir in north of Iran were monitored. Water samples were collected from different locations of the reservoir in June, July and September of 2015 and in February 2016. Water samples were extracted with dichloromethane solvent and quantified using gas chromatography and mass spectrometry analyses. The results showed that all pesticides were detected for all periods and include dichlorvos, trifluralin, diazinon, methyl parathion, fenitrothion, malathion, profenofos and ethion. The highest concentrations were found in the summer that is related to malathion (on average 0.78 μg?L^?1). In midwinter, no pesticide residues were detected. The results showed that concentration of single and total pesticides for all stations were greater than the maximum contamination level of the European Economic Commission.     

The results of trabeculectomy using a sutureless scleral tunnel technique

Purpose To evaluate the surgical outcome in terms of intraocular pressure (IOP) control and safety of procedure using a sutureless scleral tunnel technique in patients with uncontrolled glaucoma. Materials and methods This was a prospective, consecutive, noncomparative interventional case series of patients undergoing trabeculectomy. The study was conducted on 19 eyes of 19 patients with medically uncontrolled glaucoma. All of the patients underwent sutureless scleral tunnel trabeculectomy and were followed for 6 months. Patient data such as sex, age, IOP, LogMAR visual acuity (LogMAR VA), antiglaucoma medications, intraoperative and postoperative complications, bleb morphology, and success rate were collected and statistically analyzed. Results Two patients were excluded because of defaulted follow-up. Mean age was 60.58 (±15.14) years, and 65% of the patients were male. Before intervention mean IOP was 29.29 (±8.22) mmHg, and mean number of antiglaucoma medications was 2.05 (±0.89). Six months after intervention, mean IOP was 15.00 (±3.82) mmHg (P < 0.001), mean number of antiglaucoma medications was 0.52 (±1.06) (P < 0.001), complete success rate was 65%, and qualified success rate was 23%. Five patients (29.4%) needed adjunctive needling bleb revision. No major intraoperative complications were encountered. Only four patients (23.5%) had microscopic hyphema and three patients (18%) had flat anterior chamber (grade I) in the immediate postoperative period that managed medically. All but four had shallow and diffuse blebs at last follow-up. Conclusion It appears that sutureless scleral tunnel trabeculectomy is a safe and effective drainage procedure for treating uncontrolled glaucoma. Larger-scale study is recommended.