Current Trends and Future Perspectives of Antimutagenic Agents

Mutation is the process leading to heritable changes in DNA caused mainly by internal and external factors. Recently, studies on mutagenic agents have been increased due to increasing in mutation-related disease. The antimutagenic effect is desired to prevent mutation on genes or to inactivate the mutagenic agent. It seems that the interest in antimutagenic substances displaying multiple mechanisms of action will be an important trend in the research and development of new antimutagenic compounds in the near future. Therefore, this chapter displays various possible mechanisms of action for antimutagenic agent and introduces different types of antimutagens, natural and synthetic, that are considered very important

Synthesis, Characterization, and In Vivo Study of Some Novel 3,4,5-Trimethoxybenzylidene-hydrazinecarbothioamides and Thiadiazoles as Anti-Apoptotic Caspase-3 Inhibitors

The present study aims to discover novel derivatives as antiapoptotic agents and their protective effects against renal ischemia/reperfusion. Therefore, a series of new thiadiazole analogues 2a–g was designed and synthesized through cyclization of the corresponding opened hydrazinecarbothioamides 1a–g, followed by confirmation of the structure via spectroscopic tools (NMR, IR and mass spectra) and elemental analyses. The antiapoptotic activity showed alongside decreasing of tissue damage induced by I/R in the kidneys of rats using N-acetylcysteine (NAC) as an antiapoptotic reference. Most of the cyclized thiadiazoles are better antiapoptotic agents than their corresponding opened precursors. Particularly, compounds 2c and 2g were the most active antiapoptotic compounds with significant biomarkers. A preliminary mechanistic study was performed through caspase-3 inhibition. Compound 2c was selected along with its corresponding opened precursor 1c. An assay of cytochrome C revealed that there is an attenuation of cytochrome C level of about 5.5-fold, which was better than 1c with a level of 4.1-fold. In caspases-3, 8 and 9 assays, compound 2c showed more potency and selectivity toward caspase-3 and 9 compared with 1c. The renal histopathological investigation indicated normal renal tissue for most of the compounds, especially 2c and 2g, relative to the control. Finally, a molecular docking study was conducted at the caspase-3 active site to suggest possible binding modes

Utilizing the time delayed PPF controller to suppress vibrations of a nonlinear system containing real power exponents in damping and restoring forces

The time delayed Positive Position Feedback (PPF) controller is utilized to suppress the primary resonance of vibrations of an excited base oscillator by real power exponents of the restoring and damping forces. Multiple scales method is conducted to get the frequency response equations. The stability of the system is studied by using the Lyapunov first method. The influences of system parameters and time delay on the system response are investigated to avoid the jump phenomenon for better system performance. Time margin is deduced for most possible values of controller gain. Analytic results are verified by numerical integration of the original system equations

Synthesis, Characterization, and In Vivo Study of Some Novel 3,4,5-Trimethoxybenzylidene-hydrazinecarbothioamides and Thiadiazoles as Anti-Apoptotic Caspase-3 Inhibitors

The present study aims to discover novel derivatives as antiapoptotic agents and their protective effects against renal ischemia/reperfusion. Therefore, a series of new thiadiazole analogues 2a–g was designed and synthesized through cyclization of the corresponding opened hydrazinecarbothioamides 1a–g, followed by confirmation of the structure via spectroscopic tools (NMR, IR and mass spectra) and elemental analyses. The antiapoptotic activity showed alongside decreasing of tissue damage induced by I/R in the kidneys of rats using N-acetylcysteine (NAC) as an antiapoptotic reference. Most of the cyclized thiadiazoles are better antiapoptotic agents than their corresponding opened precursors. Particularly, compounds 2c and 2g were the most active antiapoptotic compounds with significant biomarkers. A preliminary mechanistic study was performed through caspase-3 inhibition. Compound 2c was selected along with its corresponding opened precursor 1c. An assay of cytochrome C revealed that there is an attenuation of cytochrome C level of about 5.5-fold, which was better than 1c with a level of 4.1-fold. In caspases-3, 8 and 9 assays, compound 2c showed more potency and selectivity toward caspase-3 and 9 compared with 1c. The renal histopathological investigation indicated normal renal tissue for most of the compounds, especially 2c and 2g, relative to the control. Finally, a molecular docking study was conducted at the caspase-3 active site to suggest possible binding modes

Synthesis, Characterization, and In Vivo Study of Some Novel 3,4,5-Trimethoxybenzylidene-hydrazinecarbothioamides and Thiadiazoles as Anti-Apoptotic Caspase-3 Inhibitors

The present study aims to discover novel derivatives as antiapoptotic agents and their protective effects against renal ischemia/reperfusion. Therefore, a series of new thiadiazole analogues 2a-g was designed and synthesized through cyclization of the corresponding opened hydrazinecarbothioamides 1a-g, followed by confirmation of the structure via spectroscopic tools (NMR, IR and mass spectra) and elemental analyses. The antiapoptotic activity showed alongside decreasing of tissue damage induced by I/R in the kidneys of rats using N-acetylcysteine (NAC) as an antiapoptotic reference. Most of the cyclized thiadiazoles are better antiapoptotic agents than their corresponding opened precursors. Particularly, compounds 2c and 2g were the most active antiapoptotic compounds with significant biomarkers. A preliminary mechanistic study was performed through caspase-3 inhibition. Compound 2c was selected along with its corresponding opened precursor 1c. An assay of cytochrome C revealed that there is an attenuation of cytochrome C level of about 5.5-fold, which was better than 1c with a level of 4.1-fold. In caspases-3, 8 and 9 assays, compound 2c showed more potency and selectivity toward caspase-3 and 9 compared with 1c. The renal histopathological investigation indicated normal renal tissue for most of the compounds, especially 2c and 2g, relative to the control. Finally, a molecular docking study was conducted at the caspase-3 active site to suggest possible binding modes.Peer reviewe

FORMULATION AND EVALUATION OF FLURBIPROFEN SUSTAINED RELEASE MATRIX TABLETS USING AN ALTERNATIVE TECHNIQUE AS POTENTIAL ECONOMIC APPROACH

Objective: Development of sustained released tablets of flurbiprofen (FP) using an alternative technique to the traditional method of wet granulation process aiming to lower labor cost of the granulation process and formulating tablets with better characteristics. Methods: Eight matrix tablets formulae of FP were prepared by the alternative technique. The various characteristics of FP prepared tablets were investigated and comparatively evaluated by FP tablets prepared by the traditional method. The release data was analyzed according to various kinetic equations. The ulcerogenic effects of some FP tablets formulae were evaluated. Results: FP tablets prepared by the alternative technique displayed the best physical characteristics. All FP prepared tablets displayed good sustained-release patterns. FP tablets prepared by the traditional method showed a progress decrease in drug dissolution by increasing matrix concentration and hence, more matrix agent or multiple granulations was needed which makes granulation process to be difficult and cost. While, FP tablets prepared by the alternative technique displayed dissolution profiles with minimal differences in-between reflecting the low labor cost of granulation process where good sustained patterns could be obtained by a minor of the matrix agent. Histologically, the ulcerogenic effects of FP on the rats were highly reduced by FP tablets prepared by the alternative technique rather than others. The release kinetics of different prepared FP tablets displayed a coupled release pattern between diffusion and dissolution. Conclusion: This work proved the potential of the alternative technique as an effective economic approach for formulating FP sustained released tablets with better characteristics and low labor cost

Controlling quarter car suspension system by proportional derivative and positive position feedback controllers with time delay

The active car suspension system is presented here to suppress the vibration of the car by applying proportional derivative (PD) and positive position feedback (PPF) controllers with time delay. The control signal output of the controller is applied electrically to the magneto-rheological (MR) damper or Electrical-rheological (ER) damper which is attached parallel to the passive components to improve the suppression of the vibration. The electrical control signal is produced by electronic circuits or programmable logic controller and the two-position sensor feedback signal which are connected to the controller. The approximate solutions of PD and PPF suspension systems are obtained by applying multiple time scales perturbation method. The effects of parameters variation of both the system and the controllers are investigated to achieve the best performance. Simulation results show good performance of the designed controllers

A Risk Allocation Model for Construction Projects in Yemen

Construction projects in Yemen always experience high levels of risk due to their complex and dynamic environments. This, in turn, impacts projects in both time and cost. Obviously, risk allocation is usually poorly assigned to project parties; leading to terrible disputes among them. Moreover, there are no suitable risk allocation models that suit the nature of Yemen's construction industry. This work endeavors to propose and apply a Risk Allocation Model (RAM), based on a simple mechanism for allocating critical risks to the responsible party in the project. In addition, the RAM aims to compare among projects, which is more risky. The construction of RAM is based on Delphi method by the expert's judgment of construction projects. Fifty four risk factors, over ten groups, are identified and used in the model development. All factors are analyzed and weighted by deploying Weighted Risk Factor (WRF) which combines the effect of a risk factor probability and its effect on time and cost. The model results identified the most important risk factors to be allocated to owner, contractor or shared between them, as well as the suitable risk action for each factor. The model is applied on a real case study through two construction projects in Yemen to test the validation. A complete comparison between the two projects is presented and a decision is introduced for contractor based on projects time and cost overruns, WRF, and risk allocated to contractor. The results emphasized that the model is easy to understand and use by the parties involved in construction projects. Further, it is characterized by flexibility in the event of variables. The RAM outcomes thus help decision-makers to come to the appropriate decision during the trade-off among different projects. Keywords: Risk allocation, Delphi method, Construction projects, Decision-making, Yemen