COX inhibition: Catalepsy and Striatum Dopaminergic-GABAergic-Glutamatergic Neurotransmission

Selective COX-2 and COX-1 inhibitors were administered (i.p. acutely) to normal and parkinsonian rats, followed by the analysis of the striatal dopamine, GABA and glutamate concentrations using the microdialysis technique, simultaneously, the catalepsy of animals was evaluated. Selective COX-2 inhibition showed improving effects on the catalepsy followed by decreasing the striatum glutamatergic-GABAergic and enhancing the dopaminergic neurotransmission. Nonetheless COX inhibition had no significant improving effects on damaged Substantia Nigra Pars Compacta (SNc) neurons

AGRO 100 Apt-Chitosan labeled with BODIPY-FL as a novel cancer diagnostic Agent

Targeted Nano-based imaging methods have been used to precisely diagnose different diseases lately. In this research, chitosan was synthesized and confirmed using Zeta Sizer and AFM. AGRO 100 Aptamer was conjugated on the surface of chitosan nanoparticles and then conjugate labeled with BODIPY-FL. Then, in vitro assays such as XTT and uptake assessment were preformed. Data showed successful synthesis of nanoparticle and conjugate. Cellular uptake in cancer cells was increased and no significant (p value<0.05) cytotoxicity has been found on normal cells. Taking everything into account, the mentioned fluorescent labeled bioconjugate seems to be an appropriate fluorescent diagnostic agent for the future in vivo studies. Introduction: Recently, many aptamers such as MUC1, A30, AGRO 100,and etc. have been found which work as therapeutic/diagnostic agents through shape complementary with their specific cancerous cell membrane overexpressed receptors. AGRO 100 is now in the second phase of clinical trials of two cancers as a therapeutic agent and it specifically targets nucleolin which is overexpressed on the cancer cells’ surface and constrains tumor growth. Nowadays, aptamer based drug delivery/ imaging is being used as a novel pharmaceutical approach in vitro/ in vivo. These aptamers based on their ability to detect cell surface disease specific biomarkers and treat diseases are termed as smart devices in Nano-Theranostics applications. Methods and Results: In the current project, chitosan was synthesized and confirmed using Zeta Sizer (size, charge and molecular weight) and AFM. Aptamer AGRO 100 (APT AS1411 ) was conjugated successfully on the surface of chitosan nanoparticles using a covalent bond (carboxyl active groups to amine active groups) using NHS and EDC, then conjugate labeled with BODIPY-FL. Conclusion: Using AGRO 100 aptamer, chitosan nanoparticles and BODIPY-FL the desired targeted fluorescent diagnostic agent was constructed. Based on the in vitro results, no significant cytotoxicity on HEK-293 has been found. Moreover, bioconjugate had a good cellular uptake on T47D cells. Taking everything into account, the mentioned fluorescent labeled bioconjugate seems to be an appropriate fluorescent diagnostic agent for the future in vivo studies

Synthesis of Novel (Technetium-99m)-(DOTA-NHS-ester)-Methionine Radio Drug as a SPECT-CT Imaging Candidate

Cancer is a disease in which a group of cells show an uncontrolled growth (Cell division beyond the normal range), invasion (Penetration into and destruction of adjacent tissues), and in some cases, metastasis (Spreading to other parts of the body via lymph or blood systems). These three destructive nature of cancerous tumors distinguish them from benign tumors. Undoubtedly, early detection of cancer is associated with an increased survival of these patients. Introduction              SPECT/CT (Single Photon Emission Computed Tomography) give us a signal for cancer diagnosis. The use of radiopharmaceuticals such as technetium improves images. Technetium is one of the famous contrast agent used in this technique, which is toxic and should be used as a complex with a ligand. In this study (Technetium-99m)-(DOTA-NHS-ester)-Methionine radio drug was synthesized. Technetium-99m is an isomer of isotope-99mTC, which is attempted by isomeric transition. Methionine is an essential amino acid which has important roles in cancerous cells. DOTA was used to conjugate with Methionine and then labeled with 99mTc to improve tumor selectivity. This synthesized radio drug would be able to nominate as a SPECT-CT imaging candidate. Methods and results In this current study, a novel structure of DOTA-NHS ester conjugated to essential amino acid methionine was synthesized, and then labeled by a radionuclide technetium. The final radiopharmaceutical characterized and then studied as a contrast agent in SPECT/CT   imaging. Conclusion (Technetium-99m)-(DOTA-NHS-ester)-Methionine synthesized radio drug showed significant (P<0.05) Cellular uptake in cancerous cells in comparison with other normal cells and Cellular toxicity was observed in those cancerous cell lines. According to the final data, the synthesized radiopharmaceutical, was detected in the tumor with high and significant appearance in SPECT/CT technique

Steroidal anti inflammatory drug betamethasone significantly alters level of striatal dopamine in a rat model of Parkinson’s disease

Many scientific efforts have been well done to investigate the effects of anti inflammatory agents on the degenerative brain diseases such as Parkinson’s (PD) or Alzheimer’s disease and their affiliated sings. Previously we showed the effectiveness of steroids on rigidity of PD and in the study for further mechanistic investigation of that observation the microdialysis technique was employed to determine the striatal dopamine changes in parkinsonian rats after administration of betamethasone (0.12, 0.24 mg/kg) respectively. Our findings showed us the significant increase in the striatal dopaminergic neurotransmission (P<0.05) after administration of betamethasone comparing to the controls. These observations suggest a new mechanism for betamethasone on striatum dopaminergic neurotransmission leading us to gather further evidence about effectiveness of betamethasone in PD

Using Improved DDAO Algorithm to Solve Economic Emission Load Dispatch Problem in the Presence of Wind Farms

In power systems planning, economic load dispatch considering the uncertainty of renewable energy sources is one of the most important challenges that researchers have been concerned about. Complex operational constraints, non-convex cost functions of power generation, and some uncertainties make it difficult to solve this problem through conventional optimization techniques. In this article, an improved dynamic differential annealed optimization (IDDAO) meta-heuristic algorithm, which is an improved version of the dynamic differential annealed optimization (DDAO) algorithm has been introduced. This algorithm has been used to solve the economic emission load dispatch (EELD) problem in power systems that include wind farms, and the performance of the proposed technique was evaluated in the IEEE 40-unit and 6-unit standard test systems. The results obtained from numerical simulations demonstrate the profound accuracy and convergence speed of the proposed IDDAO algorithm compared to conventional optimization algorithms including, PSO, GSA, and DDAO, while independent runs indicate the robustness and stability of the proposed algorithm