Revisiting aminocoumarins for the treatment of melioidosis.

Burkholderia pseudomallei causes melioidosis, a potentially lethal disease that can establish both chronic and acute infections in humans. It is inherently recalcitrant to many antibiotics, there is a paucity of effective treatment options and there is no vaccine. In the present study, the efficacies of selected aminocoumarin compounds, DNA gyrase inhibitors that were discovered in the 1950s but are not in clinical use for the treatment of melioidosis were investigated.

Virulence of the emerging pathogen, , depends upon the -linked oligosaccharyltransferase, PglL.

We sought to characterize the contribution of the -OTase, PglL, to virulence in two spp. by comparing isogenic mutants in with the related species, . We utilized an array of assays in addition to and murine models to assess virulence of the mutant and wild-type strains in each species.

Adaption of the ex vivo mycobacterial growth inhibition assay for use with murine lung cells.

In the absence of a correlate(s) of protection against human tuberculosis and a validated animal model of the disease, tools to facilitate vaccine development must be identified. We present an optimised ex vivo mycobacterial growth inhibition assay (MGIA) to assess the ability of host cells within the lung to inhibit mycobacterial growth, including Bacille Calmette-Guérin (BCG) and Mycobacterium tuberculosis (MTB) Erdman. Growth of BCG was reduced by 0.

Preclinical assessment of a new live attenuated Mycobacterium tuberculosis Beijing-based vaccine for tuberculosis.

Tuberculosis still claims more lives than any other pathogen, and a vaccine better than BCG is urgently needed. One of the challenges for novel TB vaccines is to protect against all Mycobacterium tuberculosis lineages, including the most virulent ones, such as the Beijing lineage. Here we developed a live attenuated M.

Oxidized Carbon Nanosphere-Based Subunit Vaccine Delivery System Elicited Robust Th1 and Cytotoxic T Cell Responses.

Subunit vaccines are safer and more stable than live vaccines although they have the disadvantage of eliciting poor immune response. To develop a subunit vaccine, an effective delivery system targeting the key elements of the protective immune response is a prerequisite. In this study, oxidized carbon nanospheres (OCNs) were used as a subunit vaccine delivery system and tuberculosis (TB) was chosen as a model disease.

High monocyte to lymphocyte ratio is associated with impaired protection after subcutaneous administration of BCG in a mouse model of tuberculosis.

The only available tuberculosis (TB) vaccine, Bacillus Calmette-Guérin (BCG), has variable efficacy. New vaccines are therefore urgently needed. Why BCG fails is incompletely understood, and the tools used for early assessment of new vaccine candidates do not account for BCG variability.

Inactivation of bpsl1039-1040 ATP-binding cassette transporter reduces intracellular survival in macrophages, biofilm formation and virulence in the murine model of Burkholderia pseudomallei infection.

Burkholderia pseudomallei, a gram-negative intracellular bacillus, is the causative agent of a tropical infectious disease called melioidosis. Bacterial ATP-binding cassette (ABC) transporters import and export a variety of molecules across bacterial cell membranes. At present, their significance in B.

[The interaction between people with Down syndrome and their siblings: an exploratory study].

The presence of a disabled person causes transformations in the family that demand a redefinition of the role of each member. Siblings, like all other members, experience frustration, acceptance, guilt and adaptation. In this respect, an attempt was made to; (a) analyze the interaction between a sibling with standard development and a sibling with Down syndrome; (b) identify what information and reaction the siblings with standard development have regarding the diagnosis of Down syndrome; (c) verify whether or not there were changes in the family context and also changes in their own lives after the birth of the sibling with Down syndrome.

CD4+ T Cells Recognizing PE/PPE Antigens Directly or via Cross Reactivity Are Protective against Pulmonary Mycobacterium tuberculosis Infection.

Mycobacterium tuberculosis (Mtb), possesses at least three type VII secretion systems, ESX-1, -3 and -5 that are actively involved in pathogenesis and host-pathogen interaction. We recently showed that an attenuated Mtb vaccine candidate (Mtb Δppe25-pe19), which lacks the characteristic ESX-5-associated pe/ppe genes, but harbors all other components of the ESX-5 system, induces CD4+ T-cell immune responses against non-esx-5-associated PE/PPE protein homologs. These T cells strongly cross-recognize the missing esx-5-associated PE/PPE proteins.

Influenza outbreaks in nursing homes with high vaccination coverage in Navarre, Spain, 2011/12.

In the 2011/12 season, three influenza outbreaks were studied in nursing homes with high vaccination coverage in Navarre, Spain. Attack rates ranged from 2.9% to 67%.

Minimizing creatine kinase variability in rats for neuromuscular research purposes.

Rat serum or plasma creatine kinase (CK) activity is widely used to evaluate myopathic processes, to test the myotoxicity of different drugs, or to analyse the benefits of emerging gene therapies in some neuromuscular disorders. However, great variability is found in this determination. The aim of this study has been to control some factors of variation in order to reduce variability and increase the reproducibility of analytical data.

Comparative acute systemic toxicity of several quinoxaline 1,4-di-N-oxides in Wistar rats.

The acute toxicity of six quinoxaline 1,4-di-N-oxides has been evaluated in an attempt to determine: a) the feasibility of testing systemic toxicity of these compounds in a very preliminary phase without an adequate formulation for in vivo administration, b) the LD50 range and the toxic target organ of these compounds in order to have an approximation of the structure-activity relationship. Quinoxaline 1,4-di-N-oxides have shown a great variety of biological activities with potential therapeutic application in cancer, malaria, etc. Problems of toxicity hinder the progression of these compounds to clinical phases.

[Correlation between clinical and laboratory data in depression. Therapeutic orientation by means of vitamins and amino acids].

This work is based upon the study of 472 cases from author's private practice. We considered the three following starting points: a) Catecholaminic hypothesis of depressive disorders such as formulated by late Prof. E.