Curcumin and N-Acetylcysteine Nanocarriers Alone or Combined with Deferoxamine Target the Mitochondria and Protect against Neurotoxicity and Oxidative Stress in a Co-Culture Model of Parkinson’s Disease

As the blood-brain barrier (BBB) prevents most compounds from entering the brain, nanocarrier delivery systems are frequently being explored to potentially enhance the passage of drugs due to their nanometer sizes and functional characteristics. This study aims to investigate whether Pluronic® F68 (P68) and dequalinium (DQA) nanocarriers can improve the ability of curcumin, n-acetylcysteine (NAC) and/or deferoxamine (DFO), to access the brain, specifically target mitochondria and protect against rotenone by evaluating their effects in a combined Transwell® hCMEC/D3 BBB and SH-SY5Y based cellular Parkinson’s disease (PD) model. P68 + DQA nanoformulations enhanced the mean passage across the BBB model of curcumin, NAC and DFO by 49%, 28% and 49%, respectively (p < 0.01, n = 6). Live cell mitochondrial staining analysis showed consistent co-location of the nanocarriers within the mitochondria. P68 + DQA nanocarriers also increased the ability of curcumin and NAC, alone or combined with DFO, to protect against rotenone induced cytotoxicity and oxidative stress by up to 19% and 14% (p < 0.01, n = 6), as measured by the MTT and mitochondrial hydroxyl radical assays respectively. These results indicate that the P68 + DQA nanocarriers were successful at enhancing the protective effects of curcumin, NAC and/or DFO by increasing the brain penetrance and targeted delivery of the associated bioactives to the mitochondria in this model. This study thus emphasises the potential effectiveness of this nanocarrier strategy in fully utilising the therapeutic benefit of these antioxidants and lays the foundation for further studies in more advanced models of PD

Micellar nanocarriers of hydroxytyrosol are protective against parkinson’s related oxidative stress in an in vitro hcmec/d3‐sh‐sy5y co‐culture system

Hydroxytyrosol (HT) is a natural phenolic antioxidant which has neuroprotective effects in models of Parkinson’s disease (PD). Due to issues such as rapid metabolism, HT is unlikely to reach the brain at therapeutic concentrations required for a clinical effect. We have previously developed micellar nanocarriers from Pluronic F68® (P68) and dequalinium (DQA) which have suita-ble characteristics for brain delivery of antioxidants and iron chelators. The aim of this study was to utilise the P68 + DQA nanocarriers for HT alone, or in combination with the iron chelator deferox-amine (DFO), and assess their physical characteristics and ability to pass the blood–brain barrier and protect against rotenone in a cellular hCMEC/D3‐SH‐SY5Y co‐culture system. Both HT and HT + DFO formulations were less than 170 nm in size and demonstrated high encapsulation efficiencies (up to 97%). P68 + DQA nanoformulation enhanced the mean blood–brain barrier (BBB) passage of HT by 50% (p < 0.0001, n = 6). This resulted in increased protection against rotenone induced cyto-toxicity and oxidative stress by up to 12% and 9%, respectively, compared to the corresponding free drug treatments (p < 0.01, n = 6). This study demonstrates for the first time the incorporation of HT and HT + DFO into P68 + DQA nanocarriers and successful delivery of these nanocarriers across a BBB model to protect against PD‐related oxidative stress. These nanocarriers warrant further investigation to evaluate whether this enhanced neuroprotection is exhibited in in vivo PD models

Robustness of the Blandford-Znajek mechanism

The Blandford-Znajek mechanism has long been regarded as a key ingredient in models attempting to explain powerful jets in AGNs, quasars, blazzars etc. In such mechanism, energy is extracted from a rotating black hole and dissipated at a load at far distances. In the current work we examine the behaviour of the BZ mechanism with respect to different boundary conditions, revealing the mechanism robustness upon variation of these conditions. Consequently, this work closes a gap in our understanding of this important scenario.Comment: 7 pages, accepted in CQ

Small animal disease surveillance: respiratory disease 2017

This report focuses on surveillance for respiratory disease in companion animals. It begins with an analysis of data from 392 veterinary practices contributing to the Small Animal Veterinary Surveillance Network (SAVSNET) between January and December 2017. The following section describes canine respiratory coronavirus infections in dogs, presenting results from laboratory-confirmed cases across the country between January 2010 and December 2017. This is followed by an update on the temporal trends of three important syndromes in companion animals, namely gastroenteritis, pruritus and respiratory disease, from 2014 to 2017. A fourth section presents a brief update on Streptococcus equi subspecies zooepidemicus in companion animals. The final section summarises some recent developments pertinent to companion animal health, namely eyeworm (Thelazzia callipaeda) infestations in dogs imported to the UK and canine influenza virus in the USA and Canada

Post-graduate education, training and extension at Central Marine Fisheries Research Institute, Cochin

In view of the increasing demand for trained personnel to meet the requirements of mariculture and brackishwater culture activities in the country, the Central Marine Fisheries Research Institute took steps to institute a post-graduate education programme In mariculture at the institute, leading to the M.Sc. and Ph.D. degrees awarded by the Cochin University of Science and Technology. Through this programme a number of post-graduates have been turned out in the subject during the past seven years. The students were given both theoretical and practical instructions in different aspects of mariculture including basic subjects like physiology, nutrition, genetics and pathology. The Scientists of the Institute constitute the faculty for the programme and a number of members of the faculty have also been trained abroad in different specialisations. The Programme also had the advantage of consultants from other countries who have contributed greatly to its improvement and also in the development of Infrastructural facilities at the Institute. As a result of the consultancy, a number of manuals on special subjects have also been published. The Krishi Vigyan Kendra and the Trainers' Training Centre handle a number of courses at the farmers level and at the trainers level based on the technologies developed at the Institute. In addition, an integrated programme of training including subjects in agriculture, animal husbandry and home management is also conducted

N-Acetylcysteine Nanocarriers Protect against Oxidative Stress in a Cellular Model of Parkinson's Disease

Oxidative stress is a key mediator in the development and progression of Parkinson’s disease (PD). The antioxidant N-acetylcysteine (NAC) has generated interest as a disease-modifying therapy for PD but is limited due to poor bioavailability, a short half-life, and limited access to the brain. The aim of this study was to formulate and utilise mitochondria-targeted nanocarriers for delivery of NAC alone and in combination with the iron chelator deferoxamine (DFO), and assess their ability to protect against oxidative stress in a cellular rotenone PD model. Pluronic F68 (P68) and dequalinium (DQA) nanocarriers were prepared by a modified thin-film hydration method. An MTT assay assessed cell viability and iron status was measured using a ferrozine assay and ferritin immunoassay. For oxidative stress, a modified cellular antioxidant activity assay and the thiobarbituric acid-reactive substances assay and mitochondrial hydroxyl assay were utilised. Overall, this study demonstrates, for the first time, successful formulation of NAC and NAC + DFO into P68 + DQA nanocarriers for neuronal delivery. The results indicate that NAC and NAC + DFO nanocarriers have the potential characteristics to access the brain and that 1000 μM P68 + DQA NAC exhibited the strongest ability to protect against reduced cell viability (p = 0.0001), increased iron (p = 0.0033) and oxidative stress (p ≤ 0.0003). These NAC nanocarriers therefore demonstrate significant potential to be transitioned for further preclinical testing for PD

Activo: Assessing the feasibility of designing and implementing a physical activity intervention for latino men

Background: No physical activity (PA) interventions have specifically targeted Latino men despite marked health disparities in this group. Therefore, we explored the feasibility of designing a PA intervention for Latino men. Methods: We conducted six qualitative interviews with Latino men and used their feedback to modify an existing PA intervention, then conducted a 12-week demonstration trial of the adapted intervention. Results: Themes from interviews included work and family conflicts and preferring team sports. In the demonstration trial of the modified intervention, participants (N = 10) increased PA from 1.3 minutes/week (SD = 4.75) at baseline to 125.5(SD = 154.86) at follow-up (p &lt; .05). Retention was high and participants expressed enthusiasm for the program. Conclusions: Existing interventions could be effectively modified to target physical activity in Latino men. © 2014 by the Men's Studies Press, LLC

Compartmentalized megakaryocyte death generates functional platelets committed to caspase-independent death

Caspase-directed apoptosis usually fragments cells, releasing nonfunctional, prothrombogenic, membrane-bound apoptotic bodies marked for rapid engulfment by macrophages. Blood platelets are functional anucleate cells generated by specialized fragmentation of their progenitors, megakaryocytes (MKs), but committed to a constitutive caspase-independent death. Constitutive formation of the proplatelet-bearing MK was recently reported to be caspase-dependent, apparently involving mitochondrial release of cytochrome c, a known pro-apoptogenic factor. We extend those studies and report that activation of caspases in MKs, either constitutively or after Fas ligation, yields platelets that are functionally responsive and evade immediate phagocytic clearance, and retain mitochondrial transmembrane potential until constitutive platelet death ensues. Furthermore, the exclusion from the platelet progeny of caspase-9 present in the progenitor accounts for failure of mitochondrial release of cytochrome c to activate caspase-3 during platelet death. Thus, progenitor cell death by apoptosis can result in birth of multiple functional anucleate daughter cells