BackgroundAmong patients with cystic fibrosis (CF), females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with Pseudomonas aeruginosa (P. aeruginosa). A role for gender hormones in the causation of the CF "gender gap" has been proposed. The female gender hormone 17β-estradiol (E2) plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others. Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1) or type 2 (Th2) lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL)-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules. Recent evidence suggests a central role for the IL-23/IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with P. aeruginosa by a Th17-mediated mechanism.ResultsExogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the P. aeruginosa strain PA508 (PA508), to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL) fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils). Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid. The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against P. aeruginosa in vitro.ConclusionsOur data show that E2 increases the severity of PA508 pneumonia in adult CF male mice, and suggest two potential mechanisms: enhancement of Th17-regulated inflammation and suppression of innate antibacterial defences. Although this animal model does not recapitulate all aspects of human CF lung disease, our present findings argue for further investigation of the effects of E2 on inflammation and infection with P. aeruginosa in the CF lung.
Epileptogenesis is the gradual process by which the healthy brain develops epilepsy. However, the neuronal circuit changes that underlie epileptogenesis are not well understood. Unfortunately, current chemically or electrically induced epilepsy models suffer from lack of cell specificity, so it is seldom known which cells were activated during epileptogenesis. We therefore sought to develop an optogenetic variant of the classical kindling model of epilepsy in which activatable cells are both genetically defined and fluorescently tagged. We briefly optogenetically activated pyramidal cells (PCs) in awake behaving mice every two days and conducted a series of experiments to validate the effectiveness of the model. Although initially inert, brief optogenetic stimuli eventually elicited seizures that increased in number and severity with additional stimulation sessions. Seizures were associated with long-lasting plasticity, but not with tissue damage or astrocyte reactivity. Once optokindled, mice retained an elevated seizure susceptibility for several weeks in the absence of additional stimulation, indicating a form of long-term sensitization. We conclude that optokindling shares many features with classical kindling, with the added benefit that the role of specific neuronal populations in epileptogenesis can be studied. Links between long-term plasticity and epilepsy can thus be elucidated.
Epilepsy is a major neurological disorder characterized by repeated seizures afflicting 1% of the global population. The emergence of seizures is associated with several comorbidities and severely decreases the quality of life of patients. Unfortunately, around 30% of patients do not respond to first-line treatment using anti-seizure drugs (ASDs). Furthermore, it is still unclear how seizures arise in the healthy brain. Therefore, it is critical to have well developed models where a causal understanding of epilepsy can be investigated. While the development of seizures has been studied in several animal models, using chemical or electrical induction, deciphering the results of such studies has been difficult due to the uncertainty of the cell population being targeted as well as potential confounds such as brain damage from the procedure itself. Here we describe novel approaches using combinations of optical and genetic methods for studying epileptogenesis. These approaches can circumvent some shortcomings associated with the classical animal models and may thus increase the likelihood of developing new treatment options.
Electrical kindling, repeated brain stimulation eventually resulting in seizures, is widely used as an animal model of epileptogenesis and epilepsy. However, the stimulation electrode used for electric kindling targets unknown neuronal populations and may introduce tissue damage and inflammation. Optogenetics can be used to circumvent these shortcomings by permitting millisecond control of activity in genetically defined neurons without gross injury or inflammation. Here we describe an easy step-by-step protocol for optogenetic kindling-optokindling-by which seizures are eventually elicited in initially healthy mice through repeated light stimulation of neurons expressing Channelrhodopsin-2 (ChR2). Chronic EEG recordings may be performed over large time scales to monitor activity while video camera monitoring may be used to assess the behavioral severity of seizures. In conclusion, with optokindling, neuroscientists can elucidate the circuit changes that underpin epilepsy while minimizing the contribution of confounding factors such as brain damage and inflammation.
Due to urbanization trend in Durres city, distance between city inhabitants and nature is increasing. Urban greenery is one of the methods to bridge this gap between people and nature. The study results were performed with the cooperation of EPER Center, professors and students of Durres “Aleksander Moisiu” University. It was focused in the estimation of O2 release from green surfaces at different areas of Durres city. The results achieved were carried out by field visits, the use of the GIS method and calculations performed based on various standard manuals. According to the results, it was concluded that the total amount of O2 release from green surfaces was 64420 kg/year or 64.4 t /year. It was also calculated that the available green surface for a resident in Durres city is only 1.05 m2 out of required 9 m2 per capita. Based on the needs of the population and the EU standards, this study suggests that the amount of O2 release should be 1.49∙ 108 kg/year or 1.49. 5∙ 105 t/year. The needed costs to be invested to achieve this O2 amount, is about 47 .65 billion ALL. Finally, it can be concluded that the low number of trees in Durres city, requires urgent provisions to improve air, and life quality of Durres citizens.
In recent years the urban population in Durres city has grown exponentially, leading to an increase of CO2 and consequently contributing on a large scale to climate change. Urban trees are basic to sequester CO2 emissions as they incorporate carbon in their biomass. The amount of C02 sequestration from green surfaces in Durres city was 50.13 ∙ 106 kg/year instead of 116.35 ∙ 106 kg/year that it should be. Increasing the amount of green vegetation, the energy that can be stored will be 3.7 ∙ 105 MWh compared with the actual value of 162,48 MWh. Consequently, water carrying capacity will be 2321 times more than the amount of water needed to maintain the present public green spaces. These data can be used to help assess the actual and potential role of green trees in reducing atmospheric CO2, a dominant greenhouse gas. This study was conducted under the project “Green lungs for our cities - Alternative and comprehensive platform for monitoring air quality, noise pollution and urban greenery to affect policies at the local level”. Measurements were performed with the cooperation of Eper Center, professors and students of “Aleksander Moisiu” University.
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