A Comprehensive Review on Molecular Mechanism Involved in Arsenic Trioxide Mediated Cerebral Neurodegenerative and Infectious Diseases.

Arsenic is an environmental toxicant and its toxicity is a global health problem affecting millions of people. Arsenic exposure occurs from natural geological sources leaching into aquifers, contaminating drinking water and may also occur from mining and other industrial processes. Both cancerous, noncancerous and immunological complications are possible after arsenic exposure. The many other target organs like lungs, thymus, spleen, liver, heart, kidney, and brain. Arsenic-mediated neuro, as well as immunotoxicity, is the main concern of this review. Long-term arsenic exposure can lead to various neurological dysfunctions, which may cause neurobehavioral defects and biochemical impairment in the brain, this might negatively affect one's quality of life in later stages. Arsenic also alters the levels of various neurotransmitters such as serotonin, dopamine and norepinephrine in the brain which produces neurotoxic effects and immunological deficiency. So, it is crucial to understand the neurotoxic mechanism of arsenic trioxide-mediated cerebro neurodegenerative and immunerelated alterations. One of the major mechanisms by which it exerts its toxic effect is through an impairment of cellular respiration by inhibition of various mitochondrial enzymes, and the uncoupling of oxidative phosphorylation. This review focuses on the various toxic mechanisms responsible for arsenic-mediated neurobehavioral and immune-related changes. Therefore, this review provides a critical analysis of mitochondrial dysfunctions, oxidative stress, glutamate excitatory, inflammatory and apoptosis-related mechanistic aspects in arsenic-mediated immunotoxicity, neurotoxicity, and neurodegenerative changes.

Neuroprotective Effect of Morinda citrifolia on Behavioural and Biochemical Deficits in PTZ-induced Kindled Mice.

INTRODUCTION: Epilepsy is a group of chronic neurological disorders characterized by seizures. Kindling, a chronic epileptic mouse model, was used to explore the epileptogenic mechanism and seek new anti-epileptics. In kindling, sub-convulsive (chemical/ electrical) stimuli were delivered repeatedly and erratically, eventually causing massive convulsions. Moreover, Morinda citrifolia (Noni) extracts are used as a remedy in ayurvedic preparations for many ailments. Noni has recently been shown to protect mice from amyloid beta-induced memory loss. OBJECTIVE: This study was used to investigate the neuroprotective potential of Morinda citrifolia in mice over pentylenetetrazol (PTZ)-induced kindling seizure. METHODS: Kindling was provoked by subsequent (one-day-gap) injections of PTZ (subconvulsive; 35 mg/kg; s.c.) for 29 days in mice. Following PTZ injection, convulsive behaviours were noted for 30 minutes. Open-field-test (locomotor activity), forced swimming test (depressive behaviors), elevated plus-maze, and passive avoidance tests were employed to evaluate cognition. Brain homogenate was used to estimate oxidative stress (glutathione, superoxide-dismutase, lipid-peroxidation) and acetylcholinesterase activity. RESULTS: PTZ-provoked kindled mice displayed depressive behaviors, impaired locomotion, cognitive dysfunctions and various biochemical changes. However, treatment with Morinda citrifolia extract (500 and 1000 mg/kg, p.o) and valproic acid (200 mg/kg, p.o) before 60 min of each PTZ injection diminished kindling scores and restored behavioural, and biochemical changes. CONCLUSION: Our findings suggest Morinda citrifolia offered neuroprotective effects against PTZinduced kindling seizures in mice, which were established by behavioural and biochemical paradigms.

A review on corona virus and treatment approaches with Allium sativam.

BACKGROUND: Recently reported cases of Covid-19 globally remind us that new diseases are coming while we are unable to provide the treatment for the same. The entire world is facing this viral attack; deaths are increasing day by day as well as infected patients too. Today, in the period of this disease, can we go to the shelter of our traditional medicines? MAIN BODY: In this article, we have taken medicines related to corona and conceptualized their mechanism, which gave us a chance to understand Garlic's mechanism of action, how Garlic can be a weapon in the lane with this disease. This article also tells how we can treat new diseases with our traditional herbs if no modern medicine has been discovered yet. CONCLUSION: The present review is based on the structure of the virus and the targeted site for the drug discovery process with important constituents of Allium sativam. The review work also explains the allicin chemical constituent of Allium sativam which has targeted therapeutic sites related to Covid-19.

Evaluation of delamination in drilling of bone.

In this paper, delamination of bone associated with drilling is investigated using design of experiments. Experiments have been planned based on L25 design of the orthogonal arrays with different conditions of drill bit, spindle speed and feed rate. Regression analysis is used to develop a mathematical model of delamination as a function of bone drilling process parameters. Analysis of variance (ANOVA) is carried out to find the significance of the developed model along with the percentage contribution of each factor on delamination. Optimum setting of bone drilling parameters for minimum delamination is determined using Taguchi optimization methodology. Finally, the results obtained are validated by conducting confirmation experiments.

Optimization of multiple quality characteristics in bone drilling using grey relational analysis.

PURPOSE: Drilling of bone is common during bone fracture treatment to fix the fractured parts with screws wires or plates. Minimally invasive drilling of the bone has a great demand as it helps in better fixation and quick healing of the broken bones. The purpose of the present investigation is to determine the optimum cutting condition for the minimization of the temperature, force and surface roughness simultaneously during bone drilling. METHOD: In this study, drilling experiments have been performed on bovine bone with different conditions of feed rate and drill rotational speed using full factorial design. Optimal level of the drilling parameters is determined by the grey relational grade (GRG) obtained from the GRA as the performance index of multiple quality characteristics. The effect of each drilling parameter on GRG is determined using analysis of variance (ANOVA) and the results obtained are validated by confirmation experiment. RESULTS: Grey relational analysis showed that the investigation with feed rate of 40 mm/min and spindle speed of 500 rpm has the highest grey relational grade and is recommended setting for minimum temperature, force and surface roughness simultaneously during bone drilling. Feed rate has the highest contribution (59.49%) on the multiple performance characteristics followed by the spindle speed (37.69%) as obtained from ANOVA analysis. CONCLUSIONS: The use of grey relational analysis will simplify the complex process of optimization of the multi response characteristics in bone drilling by converting them into a single grey relational grade. The use of the above suggested methodology can greatly minimize the bone tissue injury during drilling.

A feasibility investigation for modeling and optimization of temperature in bone drilling using fuzzy logic and Taguchi optimization methodology.

Drilling of bone is a common procedure in orthopedic surgery to produce hole for screw insertion to fixate the fracture devices and implants. The increase in temperature during such a procedure increases the chances of thermal invasion of bone which can cause thermal osteonecrosis resulting in the increase of healing time or reduction in the stability and strength of the fixation. Therefore, drilling of bone with minimum temperature is a major challenge for orthopedic fracture treatment. This investigation discusses the use of fuzzy logic and Taguchi methodology for predicting and minimizing the temperature produced during bone drilling. The drilling experiments have been conducted on bovine bone using Taguchi's L25 experimental design. A fuzzy model is developed for predicting the temperature during orthopedic drilling as a function of the drilling process parameters (point angle, helix angle, feed rate and cutting speed). Optimum bone drilling process parameters for minimizing the temperature are determined using Taguchi method. The effect of individual cutting parameters on the temperature produced is evaluated using analysis of variance. The fuzzy model using triangular and trapezoidal membership predicts the temperature within a maximum error of ±7%. Taguchi analysis of the obtained results determined the optimal drilling conditions for minimizing the temperature as A3B5C1.The developed system will simplify the tedious task of modeling and determination of the optimal process parameters to minimize the bone drilling temperature. It will reduce the risk of thermal osteonecrosis and can be very effective for the online condition monitoring of the process.

Modelling and optimization of temperature in orthopaedic drilling: an in vitro study.

This present investigation uses the Taguchi and response surface methodology (RSM) for modelling and optimization of the temperature produced during bone drilling. The drilling of bone is a common procedure in orthopaedic surgery to produce hole for screw insertion to fixate the fracture devices and implants. A major problem which is encountered during such a procedure is the increase in temperature of the bone due to the plastic deformation of chips and the friction between the bone and the drill. The increase in temperature can result in thermal osteonecrosis which may delay healing or reduce the stability and strength of the fixation. The drilling experiments are conducted on poly-methyl-meth-acrylate (PMMA) (as a substitute for bone) using Taguchi's L27 experimental design technique. The cutting parameters used are drill diameter, feed rate and cutting speed. The optimum cutting parameters for minimum temperature are determined by using S/N ratios and the effect of individual cutting parameters on temperature produced is evaluated using analysis of variance (ANOVA). A second-order model is established between the drilling parameters and temperature using RSM. The experimental results show that the drill diameter is the most significant drilling parameter affecting the temperature during drilling followed by cutting speed and feed, respectively. The values predicted and the values obtained from experiment are fairly close, which indicates that the developed RSM model can be effectively used to predict the temperature in orthopaedic drilling.

Drilling of bone: A comprehensive review.

BACKGROUND: Bone fracture treatment usually involves restoring of the fractured parts to their initial position and immobilizing them until the healing takes place. Drilling of bone is common to produce hole for screw insertion to fix the fractured parts for immobilization. Orthopaedic drilling during surgical process causes increase in the bone temperature and forces which can cause osteonecrosis reducing the stability and strength of the fixation. METHODS: A comprehensive review of all the relevant investigations carried on bone drilling is conducted. The experimental method used, results obtained and the conclusions made by the various researchers are described and compared. RESULT: Review suggests that the further improvement in the area of bone drilling is possible. The systematic review identified several consequential factors (drilling parameters and drill specifications) affecting bone drilling on which there no general agreement among investigators or are not adequately evaluated. These factors are highlighted and use of more advanced methods of drilling is accentuated. The use of more precise experimental set up which resembles the actual situation and the development of automated bone drilling system to minimize human error is addressed. CONCLUSION: In this review, an attempt has been made to systematically organize the research investigations conducted on bone drilling. Methods of treatment of bone fracture, studies on the determination of the threshold for thermal osteonecrosis, studies on the parameters influencing bone drilling and methods of the temperature measurement used are reviewed and the future work for the further improvement of bone drilling process is highlighted.