Curcumin-loaded nanoemulsion improves haemorrhagic stroke recovery in wistar rats.

Cerebrovascular diseases are currently a major global health problem. Considering the limitations of current therapy, the search for new alternatives for the treatment of these diseases is necessary and, in this context, curcumin, a molecule that has neuroprotective properties already described in the literature. A limiting factor when considering therapies for the nervous tissue is the presence of the blood-brain barrier which stimulates the search for new drug delivery strategies. In this context, nanoencapsulation seems to be a promising alternative. In this work, we compared the protective effects of free and nanoemulsified curcumin after intracerebral haemorrhage induced by collagenase (ICH) in Wistar rats. Injury area, motor activity, oxidative stress in the brain and serum biochemical parameters were investigated. Two hours after surgery, the first dose was injected intraperitoneally, followed by 24 and 48 h administration. Behavioural analysis was performed through 3 different tests: open field, beam walking and foot fault (24, 48 and 72 h respectively). At the end of the recovering time (3 days after injury), the animals were euthanized and the brain (for analysis of injury area and oxidative stress), blood (for biochemical parameters), kidney and liver (for histopathological examination) were investigated. Curcumin nanoemulsion 30 mg/kg was able to improve behavioural recovery, reduce the size of the haematoma and attenuate the weight loss caused by ICH. In terms of oxidative parameters, we observed that curcumin nanoemulsion modulated antioxidant responses with therapeutic potential against ICH. Only discrete results in few parameters were found with free-curcumin in the same dose.

Quantifying airborne dispersal routes of pathogens over continents to safeguard global wheat supply.

Infectious crop diseases spreading over large agricultural areas pose a threat to food security. Aggressive strains of the obligate pathogenic fungus Puccinia graminis f.sp. tritici (Pgt), causing the crop disease wheat stem rust, have been detected in East Africa and the Middle East, where they lead to substantial economic losses and threaten livelihoods of farmers. The majority of commercially grown wheat cultivars worldwide are susceptible to these emerging strains, which pose a risk to global wheat production, because the fungal spores transmitting the disease can be wind-dispersed over regions and even continents 1-11 . Targeted surveillance and control requires knowledge about airborne dispersal of pathogens, but the complex nature of long-distance dispersal poses significant challenges for quantitative research 12-14 . We combine international field surveys, global meteorological data, a Lagrangian dispersion model and high-performance computational resources to simulate a set of disease outbreak scenarios, tracing billions of stochastic trajectories of fungal spores over dynamically changing host and environmental landscapes for more than a decade. This provides the first quantitative assessment of spore transmission frequencies and amounts amongst all wheat producing countries in Southern/East Africa, the Middle East and Central/South Asia. We identify zones of high air-borne connectivity that geographically correspond with previously postulated wheat rust epidemiological zones (characterized by endemic disease and free movement of inoculum) 10,15 , and regions with genetic similarities in related pathogen populations 16,17 . We quantify the circumstances (routes, timing, outbreak sizes) under which virulent pathogen strains such as 'Ug99' 5,6 pose a threat from long-distance dispersal out of East Africa to the large wheat producing areas in Pakistan and India. Long-term mean spore dispersal trends (predominant direction, frequencies, amounts) are summarized for all countries in the domain (Supplementary Data). Our mechanistic modelling framework can be applied to other geographic areas, adapted for other pathogens and used to provide risk assessments in real-time 3 .

Large-Scale Atmospheric Dispersal Simulations Identify Likely Airborne Incursion Routes of Wheat Stem Rust Into Ethiopia.

In recent years, severe wheat stem rust epidemics hit Ethiopia, sub-Saharan Africa's largest wheat-producing country. These were caused by race TKTTF (Digalu race) of the pathogen Puccinia graminis f. sp. tritici, which, in Ethiopia, was first detected at the beginning of August 2012. We use the incursion of this new pathogen race as a case study to determine likely airborne origins of fungal spores on regional and continental scales by means of a Lagrangian particle dispersion model (LPDM). Two different techniques, LPDM simulations forward and backward in time, are compared. The effects of release altitudes in time-backward simulations and P. graminis f. sp. tritici urediniospore viability functions in time-forward simulations are analyzed. Results suggest Yemen as the most likely origin but, also, point to other possible sources in the Middle East and the East African Rift Valley. This is plausible in light of available field surveys and phylogenetic data on TKTTF isolates from Ethiopia and other countries. Independent of the case involving TKTTF, we assess long-term dispersal trends (>10 years) to obtain quantitative estimates of the risk of exotic P. graminis f. sp. tritici spore transport (of any race) into Ethiopia for different 'what-if' scenarios of disease outbreaks in potential source countries in different months of the wheat season.

An assessment of the doses received by members of the public in Japan following the nuclear accident at Fukushima Daiichi nuclear power plant.

The earthquake and tsunami on 11 March 2011, centred off the east coast of Japan, caused considerable destruction and substantial loss of life along large swathes of the Japanese coastline. The tsunami damaged the Fukushima Daiichi nuclear power plant (NPP), resulting in prolonged releases of radioactive material into the environment. This paper assesses the doses received by members of the public in Japan. The assessment is based on an estimated source term and atmospheric dispersion modelling rather than monitoring data. It is evident from this assessment that across the majority of Japan the estimates of dose are very low, for example they are estimated to be less than the annual average dose from natural background radiation in Japan. Even in the regions local to Fukushima Daiichi NPP (and not affected by any form of evacuation) the maximum lifetime effective dose is estimated to be well below the cumulative natural background dose over the same period. The impact of the urgent countermeasures on the estimates of dose was considered. And the relative contribution to dose from the range of exposure pathways and radionuclides were evaluated. Analysis of estimated doses focused on the geographic irregularity and the impact of the meteorological conditions. For example the dose to an infant's thyroid received over the first year was estimated to be greater in Hirono than in the non-evacuated region of Naraha, despite Hirono being further from the release location. A number of factors were identified and thought to contribute towards this outcome, including the local wind pattern which resulted in the recirculation of part of the release. The non-uniform nature of dose estimates strengthens the case for evaluations based on dispersion modelling.

Probucol mitigates streptozotocin-induced cognitive and biochemical changes in mice.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by synaptic loss and cognitive impairments. Although AD is the most prevalent aging-related neurodegenerative disease, therapeutic strategies remain palliative. Recent studies have shown that probucol presents neuroprotective effects in experimental models of neurodegenerative disease. The present study aimed to investigate the potential protective effects of probucol against streptozotocin (STZ)-induced cognitive impairment and hippocampal biochemical changes (oxidative stress-related parameters, acetylcholinesterase (AChE) activity, cholesterol levels and ß-secretase (BACE) protein levels) in mice. Adult Swiss mice received STZ [150 µg/bilateral, i.c.v.], and treated daily with probucol (≅10 mg/kg/day, in drinking water, for 5 weeks,). Twenty-one days after i.c.v. administrations, STZ-infused animals displayed significant deficits in cognition (evaluated in the displaced and new object recognition tasks), which were paralleled by a significant increase in hippocampal AChE activity. Moreover, STZ-infused mice showed increased levels of BACE and decreased glutathione reductase (GR) activity in the hippocampus compared with the control group. Probucol treatment significantly protected against the behavioral and hippocampal biochemical changes induced by STZ. However, it was unable to prevent STZ-induced increase of hippocampal BACE levels and did not change hippocampal cholesterol levels. It is noteworthy that probucol treatment increased the glutathione peroxidase (GPx) activity per se independent of STZ injection. The present findings are the first to show that i.c.v. STZ infusions are able to increase hippocampal BACE expression. Moreover, the results also show that probucol can counteract STZ-induced cognitive impairments and biochemical parameters independently of potential modulator effects toward BACE levels. The study is the first to report the protective effects of probucol against STZ-induced biochemical hippocampal changes and behavioral impairments, rendering this compound a promising molecule for further pharmacological studies on the search for therapeutic strategies to treat or prevent AD.

ß-Caryophyllene protects the C6 glioma cells against glutamate-induced excitotoxicity through the Nrf2 pathway.

ß-Caryophyllene (BCP), a natural bicyclic sesquiterpene present in several essential oils, displays analgesic and anti-inflammatory properties in vitro and in vivo. Astrocytes are a major class of glial cells that regulate extracellular ion balance, repair and scarring processes in the CNS following neuroinflammatory conditions and traumatic injuries. This study sought to determine the protective effect of BCP against glutamate (Glu)-induced cytotoxicity in the C6 glioma cell line on neurochemical parameters as well as their biochemical mechanism. Glu increases intracellular reactive oxygen species (ROS) production and induces mitochondrial dysfunction as well as decreasing antioxidant defenses such as glutathione (GSH) and glutathione peroxidase activity. BCP prevented C6 cells from Glu-induced cytotoxicity by modulating the cellular antioxidant response, mainly by inhibiting ROS production and reestablishing the mitochondrial membrane potential (Δψm). Moreover, BCP per se induced the nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) which was reflected by improvement in the cellular GSH antioxidant system. Taken together, our results suggest that cytoprotective effects of BCP were mediated by the amelioration of cellular antioxidant responses via Nrf2 activation, which is, in part, dependent on cannabinoid receptor type 2 (CB2R) activation. This functional nonpsychoactive CB2R ligand, could represent an important molecule for protection of glial cells against oxidative stress induced by glutamate.

Positive correlation between elevated plasma cholesterol levels and cognitive impairments in LDL receptor knockout mice: relevance of cortico-cerebral mitochondrial dysfunction and oxidative stress.

Convergent epidemiological, clinical, and experimental findings indicate that hypercholesterolemia contributes to the onset of Alzheimer's disease (AD)-like dementia, but the exact underlying mechanisms remains unknown. In this study, we evaluated the cognitive performance of mice submitted to a model of hypercholesterolemia, as well as its relationship with mitochondrial dysfunction and oxidative stress, two key events involved in AD pathogenesis. Wild-type C57bl/6 or low density lipoprotein receptor (LDLr)-deficient mice were fed with either standard or cholesterol-enriched diet for a 4-week period and tested for spatial learning and memory in the object location task. LDLr⁻/⁻ mice displayed spatial learning and memory impairments regardless of diet. Moreover, LDLr⁻/⁻ mice fed cholesterol-enriched diet presented a significant decrease in the mitochondrial complexes I and II activities in the cerebral cortex, which were negatively correlated with respective blood cholesterol levels. Additionally, hypercholesterolemic LDLr⁻/⁻ mice presented a significant decrease in glutathione levels, about 40% increase in the thiobarbituric acid-reactive substances levels, as well as an imbalance between the peroxide-removing-related enzymes glutathione peroxidase/glutathione reductase activities in the cerebral cortex. These findings indicate a significant relationship between hypercholesterolemia, cognitive impairment, and cortico-cerebral mitochondrial dysfunctional/oxidative stress. Because of the involvement of such alterations in AD patients, our data render this mouse model of hypercholesterolemia a useful approach to comprehend the molecular events mediating AD pathogenesis.

Key factors in imprecision in radiological emergency response assessments using the NAME model.

In the very early stages of response to an accidental release of radioactivity leading to environmental contamination, it is likely that only limited measurements of radioactivity in the local environment will be available on which to base decisions concerning protection measures and radiation monitoring activities. Model predictions will be used to aid understanding of the radiological situation and to form a basis for emergency health protection decisions. This paper presents an analysis of the relative importance of contributors to the imprecision associated with emergency response calculations based on a few off-site measurements, using predictions from the UK Met Office's NAME III (Numerical Atmospheric dispersion Modelling Environment version 5.2) dispersion model. The results presented extend those from a previous study in which a simple Gaussian plume model was used and confirm the key parameters contributing to imprecision. The potential extent of the sheltering countermeasure resulting from a hypothetical release in real weather conditions occurring in 2007 and 2008 is also presented.

Evacuation decisions in a chemical air pollution incident: cross sectional survey.

OBJECTIVE: To compare the health outcomes in sheltered and evacuated populations after a chemical incident in a plastics factory. DESIGN: Cross sectional survey. SETTING: Urban area in southwest England. PARTICIPANTS: 1750 residents from the area exposed to the chemical smoke, of which 472 were evacuated and the remaining 1278 were advised to shelter indoors. MAIN OUTCOME MEASURE: Number of adverse health symptoms. A case was defined by the presence of four or more symptoms. MAIN RESULTS: 1096 residents (63%; 299 evacuated, 797 sheltered) provided data for analyses. The mean symptom score and proportion of cases were higher in evacuated people than in the sheltered population (evacuated: symptom score 1.9, cases 19.7% (n = 59); sheltered: symptom score 1.0, cases 9.5% (n = 76); P < 0.001 for both). The difference between the two groups attenuated markedly at the end of two weeks from the start of the incident. The two main modifiable risk factors for the odds of becoming a case were evacuation (odds ratio 2.5, 95% confidence interval 1.7 to 3.8) and direct exposure to smoke for more than two hours on the first day of the incident (2.0, 1.7 to 2.3). The distance of residence from the factory or level of exposure before intervention (first six hours) had little effect on the odds of a person becoming a case. CONCLUSIONS: Sheltering may have been a better protective action than evacuation in this chemical incident, which is consistent with the prevailing expert view. Although this study has limitations, it is based on a real event. Evacuations carry their own risks and resource implications; increased awareness may help to reduce unnecessary evacuations in the future.

Minimally invasive, nonendoscopic saphenectomy for coronary bypass surgery.

In 200 consecutive patients who underwent elective and emergency coronary bypass surgery, a minimally invasive, nonendoscopic technique for greater saphenous vein harvesting was used and the clinical results evaluated. The technique is easy, rapid, and routinely applicable in elective and emergency coronary bypass procedures. The cosmetic effect is excellent and the saphenectomy-related morbidity low.