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Moom Sinn Aw,1 Kamarul A Khalid,2,3 Karan Gulati,1 Gerald J Atkins,2 Peter Pivonka,4 David M Findlay,2 Dusan Losic11School of Chemical Engineering, 2Discipline of Orthopaedics and Trauma, The University of Adelaide, Adelaide, SA, Australia; 3Department of Orthopaedics, Traumatology and Rehabilitation, Faculty of Medicine, International Islamic University Malaysia, Kuantan, Pahang, Malaysia; 4Engineering Computational Biology Group, School of Computer Science and Software Engineering, The University of Western Australia, Perth, WA, AustraliaPurpose: The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti) wires generated with titania nanotube (TNT) arrays as drug-releasing implants for local drug deliveryMethods: Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B) was used as the model drug, loaded inside the TNT–Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0–5 mm) and horizontal (0–10 mm) distances from the implant surface were obtained at a range of release times from 1 hour to 5 days.Results: Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT–Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex vivo showed a consistent gradual release of model drug from the TNT–Ti implants, with a characteristic three-dimensional distribution into the surrounding bone, over a period of 5 days. The parameters including the flow rate of bone culture medium, differences in trabecular microarchitecture between bone samples, and mechanical loading were found to have the most significant influence on drug distribution in the bone.Conclusion: These results demonstrate the utility of the Zetos™ system for ex vivo drug-release studies in bone, which can be applied to optimize the delivery of specific therapies and to assist in the design of new drug delivery systems. This method has the potential to provide new knowledge to understand drug distribution in the bone environment and to considerably improve existing technologies for local administration in bone, including solving some critical problems in bone therapy and orthopedic implants.Keywords: local drug delivery, Zetos bone bioreactor, drug-releasing implant, drug diffusion

Karan Gulati1,2, Moom Sinn Aw1, Dusan Losic1,21Ian Wark Research Institute, The University of South Australia, Adelaide, SA, Australia; 2School of Chemical Engineering, The University of Adelaide, Adelaide, SA, AustraliaAbstract: The blood–brain barrier (BBB) blocks the passage of active molecules from the blood which makes drug delivery to the brain a challenging problem. Oral drug delivery using chemically modified drugs to enhance their transport properties or remove the blocking of drug transport across the BBB is explored as a common approach to address these problems, but with limited success. Local delivery of drugs directly to the brain interstitium using implants such as polymeric wafers, gels, and catheters has been recognized as a promising alternative particularly for the treatment of brain cancer (glioma) and neurodegenerative disorders. The aim of this study was to introduce a new solution by engineering a drug-releasing implant for local drug delivery in the brain, based on titanium (Ti) wires with titania nanotube (TNT) arrays on their surfaces. Drug loading and drug release characteristics of this system were explored using two drugs commonly used in oral brain therapy: dopamine (DOPA), a neurotransmitter agent; and doxorubicin (DOXO), an anticancer drug. Results showed that TNT/Ti wires could provide a considerable amount of drugs (>170 µg to 1000 µg) with desirable release kinetics and controllable release time (1 to several weeks) and proved their feasibility for use as drug-releasing implants for local drug delivery in the brain.Purpose: In this report, a new drug-releasing platform in the form of nanoengineered Ti wires with TNT arrays is proposed as an alternative for local delivery of chemotherapeutics in the brain to bypass the BBB. To prove this concept, drug loading and release characteristics of two drugs important for brain therapy (the neurotransmitter DOPA and the anticancer drug DOXO) were explored.Methods: Titania nanotube arrays on the surface of Ti wires (TNT/Ti) were fabricated using a simple anodization process, followed by separate loading of two drugs (DOPA and DOXO) inside the nanotube structures. The loading and in vitro release characteristics of prepared TNT/Ti implants were examined using thermogravimetric analysis (TGA) UV-Vis spectroscopy.Results: Scanning electron microscopy studies confirmed that well-ordered, vertically aligned, densely packed nanotube arrays with an average diameter of 170 nm and length 70 µm were formed on the surface of TNT/Ti wires. TGA results showed a total drug loading of 170 µg and 1200 µg inside the TNTs for DOPA and DOXO respectively. Two-phase drug release behavior was observed including a fast release (burst) for the first 6 hours and a prolonged slow release phase for 8 days, both with acceptable dosage and desirable release kinetics. The physical, structural, loading and release characteristics of prepared TNT/Ti implants showed several advantages in comparison with existing and clinically proved brain implants.Conclusion: Our results confirmed that TNT/Ti wires can be successfully employed as a suitable platform to release neurotransmitters such as DOPA and anticancer drugs such as DOXO. Hence, they are a feasible alternative as drug-releasing implants for local drug delivery in the brain to combat neurodegenerative disorders or brain tumors.Keywords: titania nanotubes, brain implants, local drug delivery, dopamine, doxorubicin

Background Utilization of maternal health care services by tribal population could be detrimental in reducing high maternal mortality in Madhya Pradesh, India. A growing body of evidence indicates the positive association between male involvement and increased use of antenatal care services. Further research is required to understand barriers and possible solutions to develop culturally appropriate interventions to engage men to promote the utilization of maternal health care services. Methods The study used qualitative data collected through 8 focus group discussions with men and women and 8 key informant interviews with either a community representative or health worker in two blocks dominated by Saharia tribes in Gwalior district, Madhya Pradesh, India in 2018. Information on the perception of utilization of maternal and child health services, male involvement, challenges and opportunities were elicited using a structured guide. Framework analysis was used to analyse the data. Results Findings document barriers at the individual (poor knowledge, fear of loss of wage, choice of home as a place of delivery), community (practices that reinforced the prevailing gender norms) and health care facility level (quality and attitude of health care providers) to male engagement in utilization of maternal health services. Community perceptions on possible solutions to address these were more likely to be gender exploitative interventions. Conclusion To promote utilization of maternal health care services among Saharia tribes, this study highlights the importance of developing gender sensitive interventions that addresses the individual, community and health care facility level barriers of male involvement and do not reinforce existing gender norms., Author(s): Saritha Nair [sup.1] , Tulsi Adhikari [sup.1] , Atul Juneja [sup.1] , K. Bal Gulati [sup.1] , Ashpinder Kaur [sup.1] , M. Vishnu Vardhana Rao [sup.1] Author Affiliations: (1) [...]

Alzheimer's disease (AD) has been closely linked to type 2 diabetes mellitus (T2DM) and insulin resistance plays a key role in the onset and development of AD. It has also been reported that NO donors play an important role in diabetes and have neuroprotective activity. The present study evaluated the effects NOS substrate, L-arginine and NOS-blocker, NG-nitro-L-arginine methyl ester (L-NAME) on cognitive functions, brain amyloid β levels and other associated biochemical markers in diabetes (T2DM)-induced AD in rats. T2DM was induced by a combination of high fat diet (HFD) and streptozotocin (STZ) (35 mg/kg, i.p.). Pretreatment with L-arginine (100 mg/kg/day) improved diabetes related biochemical parameters viz. plasma glucose, triglycerides and cholesterol. In addition, L-arginine also improved insulin levels and glucose tolerance. On the other hand, NO synthase inhibitor, L-NAME (10 mg/kg), did not have much influence on these parameters. Further, L-arginine treatment showed ameliorative effects on cognitive deficits seen in the Morris water maze (MWM) test when compared to the vehicle (saline) treated group and similar results were observed in the passive avoidance test. These neurobehavioural changes were associated with predictable modulations in Aβ levels in hippocampus and cortex in HFD + STZ + saline group, which were attenuated in the L-arginine, but not in the L-NAME-treated group. Our results indicate that L-arginine could be a considered a potential therapeutic strategy to attenuate the diabetes induced cognitive deficits in AD. [ABSTRACT FROM AUTHOR]

Image processing based catheter selection is an advanced technique in which three dimensional (3D) curve of the coronary arteries and aorta were projected on a two dimensional (2D) plane and the parameters were estimeted. During the projection of 3D curve to 2D plane there was information loss which affected the final results. In present study, an algorithm for selecting an optimal plane which reduced the information loss during the projection phase was suggested. The proposed method was evaluated on the ground truth and the obtained intraclass correlation coefficients and their 95% confidence intervals had the confidence limit between 0.996 -1.00. The results showed that the proposed method minimized information loss during projection. It minimized mean error in angle calculation to 2% as compared to the existing algorithm that had 6% error rate. The proposed method was time efficient and it estimated the parameters from the patient image data on optimal plane. [ABSTRACT FROM AUTHOR]