Use of adjuvants in the treatment of Acinetobacter baumannii

The current antibiotic crisis to treat infections by Acinetobacter baumannii is linked with the increase of antimicrobial resistance and the lack of development of new antimicrobial drugs. For this reason, new alternatives for the treatment and control of infections by A. baumannii are necessary. Several studies have reported the effect of adjuvants to restore the efficacy of existing antimicrobial agents. Herein, we analyzed the main results on the development of adjuvant drugs, as monotherapy or in combination therapy with existing antimicrobial agents, which have shown promising results in vitro and in vivo. However, caution is needed and further extensive in vivo studies have to be performed to confirm the potential use of these adjuvants as true therapeutic alternatives.     

Profound CD4+ T lymphocytopenia in human immunodeficiency virus negative individuals,improved with anti-human herpes virus treatment

Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immunodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lymphocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diagnosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings'' health.     

Modeling of the dielectric properties of trabecular bone samples at microwave frequency

In this paper, the dielectric properties of human trabecular bone are evaluated under physiological condition in the microwave range. Assuming a two components medium, simulation and experimental data are presented and discussed. A special experimental setup is developed in order to deal with inhomogeneous samples. Simulation data are obtained using finite difference time domain from a realistic sample. The bone mineral density of the samples are also measured. The simulation and experimental results of the present study suggest that there is a negative relation between bone volume fraction (BV/TV) and permittivity/conductivity: the higher the BV/TV, the lower the permittivity/conductivity. This is in agreement with the recently published in vivo data.     

Alpha and Beta Subunit Immunoreactivity of Reference Preparations used in the Radioimmunoassay of Follicle Stimulating and Luteinizing Hormones in Serum

The 2nd IRP-HMG, the 1st IS, and LER 907 have been widely used in standard FSH and LH RIA systems to measure circulating levels of FSH and LH in human serum. In these systems, the dose-response curves elicited by the preparations were parallel to each other and to that of serum samples tested. When these materials were studied in the homologous α and β-hLH RIA systems, the three hormones and a serum sample used as internal control in all assays, displayed a higher degree of contamination with α than with β-hLH subunits. On weight basis, the α/β ratios were 18.0, 18.7, 6.7, and 13.0, for the 2nd IRP-HMG, 1st IS, LER 907 and serum, respectively. In the homologous α and β-hFSH RIA's, the highest contamination with α-hFSH was displayed by LER 907 (α/β ratio :10), the α/β ratios for the 2nd IRP-HMG and 1st IS were 2.2 and 1.1, respectively. The serum sample contained about 6.2 ng equivalent of α-hFSH/ml; β-hFSH was not detected.

The α-subunits of glycoprotein hormones are interchangeable and responsible for the “within species” cross-reactivity of the hormones. Therefore, employing an antisera raised against native FSH and LH in which the antigenic sites are α-directed, the reference materials and the circulating gonadotropins which contain an excess of α over β-subunit, would elicit dose-response curves parallel to each other. Because various batches of RIA reagents may not exhibit similar characteristics, before these materials are used in standard RIA's, the immunological similarity of the reference preparation and test samples must be established with the reagents used in each laboratory.     

Mathematical and Pharmacokinetic Approaches for the Design of New 3D Printing Inks Using Ricobendazole

Pharmaceutical Research - 3D printing (3DP) makes it possible to obtain systems that are not achievable with current conventional methods, one of them, sustained release floating systems. Floating...     

TLR2 activation in corneal stromal cells by Staphylococcus aureus‐induced keratitis

The Toll‐Like Receptor 2 (TLR2) plays an active and important role in Staphylococcus aureus‐induced chronic ocular inflammation. The aim of this study was to investigate the expression and function of TLR2 of corneal stromal cells in ex vivo rabbit model of S. aureus keratitis. Corneal buttons with sclera rims placed in an ex vivo air‐interface organ culture were assigned to two groups: corneas with epithelial and stromal abrasions. Each group was then divided into two sub‐groups exposed to UV‐killed S. aureus ATCC 6538P and S. aureus ATCC 29213, respectively. TLR2 and IL‐8 mRNA expressions were analyzed by quantitative real‐time RT‐PCR. TLR2 localization was visualized by immunofluorescence analysis. The results demonstrated that TLR2 and IL‐8 mRNA were significantly expressed in the stromal cells of the groups exposed to S. aureus strains. Moreover, it has been demonstrated that, after corneal injury, keratocytes differentiated into myofibroblasts became able to express TLR2 only when exposed to S. aureus. Identification of mechanisms regulation of corneal TLRs may lead to development of therapeutic interventions aimed at controlling corneal inflammation. This ex vivo model can be used to clarify the molecular events of bacterial‐corneal tissue interactions and their inflammatory consequences.     

Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis

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Air- breathing in fish: Air- breathing organs and control of respiration: Nerves and neurotransmitters in the air-breathing organs and the skin

In fishes, exploitation of aerial gas exchange has evolved independently many times, involving a variety of air-breathing organs. Indeed, air-breathing occurs in at least 49 known families of fish (Graham, 1997). Many amphibious vertebrates, at some stage of their development are actually trimodal breathers that use various combinations of respiratory surfaces to breath both water (skin and/or gill) and air (skin and/or lung). The present review examines the evolutionary implications of air-breathing organs in fishes and the morphology of the peripheral receptors and the neurotransmitter content of the cells involved in the control of air-breathing. Control of breathing, whether gill ventilation or air-breathing, is influenced by feedback from peripheral and/or central nervous system receptors that respond to changes in PO2, PCO2 and/or pH. Although the specific chemoreceptors mediating the respiratory reflexes have not been conclusively identified, studies in water-breathing teleosts have implicated the neuroepithelial cells (NECs) existing in gill tissues as the O2 sensitive chemoreceptors that initiate the cardiorespiratory reflexes in aquatic vertebrates. Some of the air-breathing fishes, such as Protopterus, Polypterus and Amia have been shown to have NECs in the gills and/or lungs, although the role of these receptors and their innervation in the control of breathing is not known. NECs have been also reported in the specialized respiratory epithelia of accessory respiratory organs (ARO’s) of some catfish species and in the gill and skin of the mudskipper Periophthalmodon schlosseri. Unlike teleosts matching an O2-oriented ventilation to ambient O2 levels, lungfishes have central and peripheral H+/CO2 receptors that control the acid-base status of the blood.