Computational modelling of the gene expression profile from acute ischaemic brain injury

The ensuing events subsequent to cerebral ischaemia are complex and multi-faceted, making it difficult to extract causal relationships between the various pathways that are altered during ischaemia. In this study, we analyse a comprehensive DNA microarray dataset of acute experimental ischaemic stroke, in an effort to elucidate key regulatory elements that participate in the triggering of the pathways that lead to tissue damage. The data suggest that genes responsible for immediate early genes, apoptosis, neurotransmitter receptors (principally glutamate), and inflammation are differentially expressed at various time points subsequent to experimental ischaemia. Using unsupervised clustering (self-organising maps) and gene regulatory networks, we were able to establish a framework within which we could place the resultant gene expression changes into. Although not yet complete, the results from this study indicate that even a complicated pathology such as ischaemia can be analysed in a biologically meaningful way using DNA microarray technology

Polymer-drug nanoconjugate – an innovative nanomedicine: challenges and recent advancements in rational formulation design for effective delivery of poorly soluble drugs.

The published manuscript is available at EurekaSelect via - See more at: http://dx.doi.org/10.2174/2211738504666160213001714Abstract Background: Over the last four decades, the use of water soluble polymers in rational formulation design has rapidly evolved into valuable drug delivery strategies to enhance the safety and therapeutic effectiveness of poorly soluble drugs, particularly anticancer drugs. Novel advances in polymer chemistry have provided new generations of well defined polymeric architectures for specific applications in polymer-drug conjugate design. However, total control of crucial parameters such as particle size, molecular weight distribution, polydispersity, localization of charges, hydrophilic-lipophilic balance and non site-specific coupling reactions during conjugation has been a serious challenge. Objective: This review briefly describes the current advances in polymer-drug nanoconjugate design and various challenges hindering their transformation into clinically useful medicines. Method: Existing literature was reviewed. Results: This review provides insights into the significant impact of covalent and non-covalent interactions between drug and polymer on drug loading [or conjugation] efficiency, conjugate stability, mechanism of drug release from the conjugate and biopharmaceutical properties of poorly soluble drugs. The utility values and application of Quality by Design principles in rational design, optimization and control of the Critical Quality Attributes [CQA] and Critical Process Parameters [CPP] that underpin the safety, quality and efficacy of the nanoconjugates are also presented. Conclusion: It was apparent that better understanding of the physicochemical properties of the nanoconjugates as well as the drug-polymer interaction during conjugation process is essential to be able to control the biodistribution, pharmacokinetics, therapeutic activity and toxicity of the nanoconjugates which will in turn enhance the prospect of successful transformation of these promising nanoconjugates into clinically useful nanomedicines

Risk in CNS drug discovery: focus on treatment of Alzheimer's Disease

Despite rapid progress in our understanding of disease mechanisms and an exploding list of new targets for therapeutic intervention, drug discovery and development remains a highly risky business. Understanding the risk involved requires appreciation of the differing perspectives of risk held by the various stakeholders involved in drug research. Risk can be reduced by thoughtful management of drug candidate selection, careful planning and program execution by a team of engaged experts, and disciplined decision making. Drug development is particularly challenging for treatments of neurodegenerative diseases such as Alzheimer's disease, in which translation from animal models of efficacy to human success is poor or unknown, the timelines for clinical study are long, and the markers of efficacy are still evolving. Despite this there are several therapies in clinical development that hold the promise of influencing this disease through novel and possibly synergistic mechanisms

Automatic extraction of angiogenesis bioprocess from text

Motivation: Understanding key biological processes (bioprocesses) and their relationships with constituent biological entities and pharmaceutical agents is crucial for drug design and discovery. One way to harvest such information is searching the literature. However, bioprocesses are difficult to capture because they may occur in text in a variety of textual expressions. Moreover, a bioprocess is often composed of a series of bioevents, where a bioevent denotes changes to one or a group of cells involved in the bioprocess. Such bioevents are often used to refer to bioprocesses in text, which current techniques, relying solely on specialized lexicons, struggle to find

Service user and caregiver involvement in mental health system strengthening in low- and middle-income countries: a cross-country qualitative study

The aims of this paper are to: (i) explore the experiences of involvement of mental health service users, their caregivers, mental health centre heads and policy makers in mental health system strengthening in three low- and middle-income countries (LMICs) (Ethiopia, Nepal and Nigeria); (ii) analyse the potential benefits and barriers of such involvement; and (iii) identify strategies required to achieve greater service user and caregiver participation. A cross-country qualitative study was conducted, interviewing 83 stakeholders of mental health services. Our analysis showed that service user and caregiver involvement in the health system strengthening process was an alien concept for most participants. They reported very limited access to direct participation. Stigma and poverty were described as the main barriers for involvement. Several strategies were identified by participants to overcome existing hurdles to facilitate service user and caregiver involvement in the mental health system strengthening process, such as support to access treatment, mental health promotion and empowerment of service users. This study suggests that capacity building for service users, and strengthening of user groups would equip them to contribute meaningfully to policy development from informed perspectives. Involvement of service users and their caregivers in mental health decision-making is still in its infancy in LMICs. Effective strategies are required to overcome existing barriers, for example making funding more widely available for Ph.D. studies in participatory research with service users and caregivers to develop, implement and evaluate approaches to involvement that are locally and culturally acceptable in LMICs

Mentoring and Quality Service Delivery in Nigerian Public Universities: Does Organizational Culture Matter?

The study sought to investigate the effect of mentoring on quality service delivery in Nigerian public Universities by adopting the cross-sectional survey research design involving the administration of a questionnaire on a sample of 1900 respondents. The structural equation modelling was used to estimate the specified model. The results showed that supervisory mentoring and career development mentoring significantly affect quality service delivery. Similarly, peer review mentoring and role modelling significantly positively affect quality service delivery. Our study shows that organisational culture moderates the relationship between mentoring and quality service delivery. The study recommends that the management of Universities in Nigeria should institutionalise mentoring programmes to support employee career development and encourage senior employees to take on the responsibility of role modelling so that younger employees could emulate their work attitudes and improve the quality of service delivery in the institutions. The study’s result bears an important implication for public universities in Nigeria which must prioritize mentoring to foster the career growth of young faculty members and enhance quality service delivery

Kinstate intervention in ethnic conflicts : Albania and Turkey compared

Albania and Turkey did not act in overtly irredentist ways towards their ethnic brethren in neighboring states after the end of communism. Why, nonetheless, did Albania facilitate the increase of ethnic conflict in Kosovo and Macedonia, while Turkey did not, with respect to the Turks of Bulgaria? I argue that kin-states undergoing transition are more prone to intervene in external conflicts than states that are not, regardless of the salience of minority demands in the host-state. The transition weakens the institutions of the kin-state. Experiencing limited institutional constraints, self-seeking state officials create alliances with secessionist and autonomist movements across borders alongside their own ideological, clan-based and particularistic interests. Such alliances are often utilized to advance radical domestic agendas. Unlike in Albania's transition environment, in Turkey there were no emerging elites that could potentially form alliances and use external movements to legitimize their own domestic existence or claims

Eco-Friendly, Green Approach for Synthesis of Bio-Active Novel 3-Aminoindazole Derivatives

In present chapter we have reported green and highly efficient method for synthesize novel series of substituted -1H-indazol-3-amine derivative (3a-h) by cyclocondensation reaction of substituted benzonitrile (1a-h) and substituted Hydrazine (2a-h) using ceric (IV) ammonium nitrate (CAN) as a catalyst, EtOH-H2O as a ecofriendly media and reaction was carried out under ultrasound irradiation green method. The structures of newly synthesized indazole derivative (3a-h) were corroborated through spectral investigation such as elemental analysis and spectral studies like IR, C13 NMR, Mass spectra and 1H NMR. The compounds were assessed for their in-vitro antimicrobial activity with pathogenic microbe comprising Gram positive bacterial strains, S. aureus and Gram negative strains E.coli, P.vulgaris, and S. typhi at different concentration. The consequence of bioassay is compared with standard drug Chloramphenicol