Pharmacological analysis of 50 kHz vocalizations in the male rat

The production of 50 kHz ultrasonic vocalizations in rats has been associated with both positive social interactions and appetitive behavioural situations. Furthermore, there is significant evidence showing that these vocalizations are controlled by the meso-limbic dopamine system. The purpose of this study was to perform a pharmacological analysis of 50 kHz calls by using dopamine and two dopamine agonists amphetamine and apomorphine, to induce calls. The acoustic parameters of the different call types were compared across each agonist. All three agonists were able to significantly induce more 50 kHz vocalizations compared to the vehicle control. Furthermore, calls elicited by apomorphine had a significantly higher bandwidth compared to those elicited by dopamine and amphetamine. All three agonists also had significantly different pharmacokinetic properties. These observations suggest that the D2 receptor sub-type is involved in the length of call bandwidths

Cancer resistance to treatment and antiresistance tools offered by multimodal multifunctional nanoparticles

Chemotherapeutic agents have limited efficacy and resistance to them limits today and will limit tomorrow our capabilities of cure. Resistance to treatment with anticancer drugs results from a variety of factors including individual variations in patients and somatic cell genetic differences in tumours. In front of this, multimodality has appeared as a promising strategy to overcome resistance. In this context, the use of nanoparticle-based platforms enables many possibilities to address cancer resistance mechanisms. Nanoparticles can act as carriers and substrates for different ligands and biologically active molecules, antennas for imaging, thermal and radiotherapy and, at the same time, they can be effectors by themselves. This enables their use in multimodal therapies to overcome the wall of resistance where conventional medicine crash as ageing of the population advance. In this work, we review the cancer resistance mechanisms and the advantages of inorganic nanomaterials to enable multimodality against them. In addition, we comment on the need of a profound understanding of what happens to the nanoparticle-based platforms in the biological environment for those possibilities to become a reality

Optimal Multi-Drug Chemotherapy Control Scheme for Cancer Treatment. Design and development of a multi-drug feedback control scheme for optimal chemotherapy treatment for cancer. Evolutionary multi-objective optimisation algorithms were used to achieve the optimal parameters of the controller for effective treatment of cancer with minimum side effects.

Cancer is a generic term for a large group of diseases where cells of the body lose their normal mechanisms for growth so that they grow in an uncontrolled way. One of the most common treatments of cancer is chemotherapy that aims to kill abnormal proliferating cells; however normal cells and other organs of the patients are also adversely affected. In practice, it¿s often difficult to maintain optimum chemotherapy doses that can maximise the abnormal cell killing as well as reducing side effects. The most chemotherapy drugs used in cancer treatment are toxic agents and usually have narrow therapeutic indices, dose levels in which these drugs significantly kill the cancerous cells are close to the levels which sometime cause harmful toxic side effects. To make the chemotherapeutic treatment effective, optimum drug scheduling is required to balance between the beneficial and toxic side effects of the cancer drugs. Conventional clinical methods very often fail to find drug doses that balance between these two due to their inherent conflicting nature. In this investigation, mathematical models for cancer chemotherapy are used to predict the number of tumour cells and control the tumour growth during treatment. A feedback control method is used so as to maintain certain level of drug concentrations at the tumour sites. Multi-objective Genetic Algorithm (MOGA) is then employed to find suitable solutions where drug resistances and drug concentrations are incorporated with cancer cell killing and toxic effects as design objectives. Several constraints and specific goal values were set for different design objectives in the optimisation process and a wide range of acceptable solutions were obtained trading off among different conflicting objectives. Abstract v In order to develop a multi-objective optimal control model, this study used proportional, integral and derivative (PID) and I-PD (modified PID with Integrator used as series) controllers based on Martin¿s growth model for optimum drug concentration to treat cancer. To the best of our knowledge, this is the first PID/I-PD based optimal chemotherapy control model used to investigate the cancer treatment. It has been observed that some solutions can reduce the cancer cells up to nearly 100% with much lower side effects and drug resistance during the whole period of treatment. The proposed strategy has been extended for more drugs and more design constraints and objectives.Libyan Ministry of Higher Educatio

Nanoparticulation of Prodrug into Medicines for Cancer Therapy

This article provides a broad spectrum about the nanoprodrug fabrication advances co-driven by prodrug and nanotechnology development to potentiate cancer treatment. The nanoprodrug inherits the features of both prodrug concept and nanomedicine know-how, attempts to solve underexploited challenge in cancer treatment cooperatively. Prodrugs can release bioactive drugs on-demand at specific sites to reduce systemic toxicity, this is done by using the special properties of the tumor microenvironment, such as pH value, glutathione concentration, and specific overexpressed enzymes; or by using exogenous stimulation, such as light, heat, and ultrasound. The nanotechnology, manipulating the matter within nanoscale, has high relevance to certain biological conditions, and has been widely utilized in cancer therapy. Together, the marriage of prodrug strategy which shield the side effects of parent drug and nanotechnology with pinpoint delivery capability has conceived highly camouflaged Trojan horse to maneuver cancerous threats