Antimicrobial activity and bioactive compounds of portuguese wild edible mushrooms methanolic extracts

The antimicrobial properties of phenolic extracts of Portuguese wild edible mushroom species (Lactarius deliciosus, Sarcodon imbricatus and Tricholoma portentosum) against pathogens were investigated. The minimal inhibitory concentrations (MICs) were evaluated for the entire mushroom, the cap and the stipe, separately; the portion of the mushroom used proved to be influenced in the results obtained, which are directly correlated with the content of total phenols and flavonoids in the extracts. The growth of Grampositive bacteria (Bacillus cereus, B. subtilis,) was well inhibited by these mushrooms, while Escherichia coli (Gramnegative bacteria) was resistant. The study on the antifungal effect of these mushrooms revealed that Candida albicans and Cryptococcus neoformans were differently inhibited for the mushrooms used

Intranasal delivery bypasses the blood-brain barrier to target therapeutic agents to the central nervous system and treat neurodegenerative disease

Intranasal delivery provides a practical, non-invasive method of bypassing the blood-brain barrier (BBB) to deliver therapeutic agents to the brain and spinal cord. This technology allows drugs that do not cross the BBB to be delivered to the central nervous system within minutes. It also directly delivers drugs that do cross the BBB to the brain, eliminating the need for systemic administration and its potential side effects. This is possible because of the unique connections that the olfactory and trigeminal nerves provide between the brain and external environment. Intranasal delivery does not necessarily require any modification to therapeutic agents. A wide variety of therapeutics, including both small molecules and macromolecules, can be targeted to the olfactory system and connected memory areas affected by Alzheimer's disease. Using the intranasal delivery system, researchers have reversed neurodegeneration and rescued memory in a transgenic mouse model of Alzheimer's disease. Intranasal insulin-like growth factor-I, deferoxamine, and erythropoietin have been shown to protect the brain against stroke in animal models. Intranasal delivery has been used to target the neuroprotective peptide NAP to the brain to treat neurodegeneration. Intranasal fibroblast growth factor-2 and epidermal growth factor have been shown to stimulate neurogenesis in adult animals. Intranasal insulin improves memory, attention, and functioning in patients with Alzheimer's disease or mild cognitive impairment, and even improves memory and mood in normal adult humans. This new method of delivery can revolutionize the treatment of Alzheimer's disease, stroke, and other brain disorders

Shifting suitability for malaria vectors across Africa with warming climates

<p>Abstract</p> <p>Background</p> <p>Climates are changing rapidly, producing warm climate conditions globally not previously observed in modern history. Malaria is of great concern as a cause of human mortality and morbidity, particularly across Africa, thanks in large part to the presence there of a particularly competent suite of mosquito vector species.</p> <p>Methods</p> <p>I derive spatially explicit estimates of human populations living in regions newly suitable climatically for populations of two key <it>Anopheles gambiae </it>vector complex species in Africa over the coming 50 years, based on ecological niche model projections over two global climate models, two scenarios of climate change, and detailed spatial summaries of human population distributions.</p> <p>Results</p> <p>For both species, under all scenarios, given the changing spatial distribution of appropriate conditions and the current population distribution, the models predict a reduction of 11.3–30.2% in the percentage of the overall population living in areas climatically suitable for these vector species in coming decades, but reductions and increases are focused in different regions: malaria vector suitability is likely to decrease in West Africa, but increase in eastern and southern Africa.</p> <p>Conclusion</p> <p>Climate change effects on African malaria vectors shift their distributional potential from west to east and south, which has implications for overall numbers of people exposed to these vector species. Although the total is reduced, malaria is likely to pose novel public health problems in areas where it has not previously been common.</p

Clinical correlates of grey matter pathology in multiple sclerosis

Traditionally, multiple sclerosis has been viewed as a disease predominantly affecting white matter. However, this view has lately been subject to numerous changes, as new evidence of anatomical and histological changes as well as of molecular targets within the grey matter has arisen. This advance was driven mainly by novel imaging techniques, however, these have not yet been implemented in routine clinical practice. The changes in the grey matter are related to physical and cognitive disability seen in individuals with multiple sclerosis. Furthermore, damage to several grey matter structures can be associated with impairment of specific functions. Therefore, we conclude that grey matter damage - global and regional - has the potential to become a marker of disease activity, complementary to the currently used magnetic resonance markers (global brain atrophy and T2 hyperintense lesions). Furthermore, it may improve the prediction of the future disease course and response to therapy in individual patients and may also become a reliable additional surrogate marker of treatment effect

Efflux pump inhibitors (EPIs) as new antimicrobial agents against Pseudomonas aeruginosa

Pseudomonas aeruginosa is an opportunistic human pathogen and one of the leading causes of nosocomial infections worldwide. The difficulty in treatment of pseudomonas infections arises from being multidrug resistant (MDR) and exhibits resistance to most antimicrobial agents due to the expression of different mechanisms overcoming their effects. Of these resistance mechanisms, the active efflux pumps in Pseudomonas aeruginosa that belong to the resistance nodulation division (RND) plays a very important role in extruding the antibiotics outside the bacterial cells providing a protective means against their antibacterial activity. Beside its role against the antimicrobial agents, these pumps can extrude biocides, detergents, and other metabolic inhibitors. It is clear that efflux pumps can be targets for new antimicrobial agents. Peptidomimetic compounds such as phenylalanine arginyl β-naphthylamide (PAβN) have been introduced as efflux pump inhibitors (EPIs); their mechanism of action is through competitive inhibition with antibiotics on the efflux pump resulting in increased intracellular concentration of antibiotic, hence, restoring its antibacterial activity. The advantage of EPIs is the difficulty to develop bacterial resistance against them, but the disadvantage is their toxic property hindering their clinical application. The structure activity relationship of these compounds showed other derivatives from PAβN that are higher in their activity with higher solubility in biological fluids and decreased toxicity level. This raises further questions on how can we compact Pseudomonas infections. Of particular importance, the recent resurgence in the use of older antibiotics such as polymyxins and probably applying stricter control measures in order to prevent their spread in clinical sittings

Transgenic technologies to induce sterility

The last few years have witnessed a considerable expansion in the number of tools available to perform molecular and genetic studies on the genome of Anopheles mosquitoes, the vectors of human malaria. As a consequence, knowledge of aspects of the biology of mosquitoes, such as immunity, reproduction and behaviour, that are relevant to their ability to transmit disease is rapidly increasing, and could be translated into concrete benefits for malaria control strategies. Amongst the most important scientific advances, the development of transgenic technologies for Anopheles mosquitoes provides a crucial opportunity to improve current vector control measures or design novel ones. In particular, the use of genetic modification of the mosquito genome could provide for a more effective deployment of the sterile insect technique (SIT) against vector populations in the field. Currently, SIT relies on the release of radiation sterilized males, which compete with wild males for mating with wild females. The induction of sterility in males through the genetic manipulation of the mosquito genome, already achieved in a number of other insect species, could eliminate the need for radiation and increase the efficiency of SIT-based strategies. This paper provides an overview of the mechanisms already in use for inducing sterility by transgenesis in Drosophila and other insects, and speculates on possible ways to apply similar approaches to Anopheles mosquitoes