9 research outputs found

    Mercury's low‐degree geoid and topography controlled by insolation‐driven elastic deformation

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    ©2015. American Geophysical UnionMercury experiences an uneven insolation that leads to significant latitudinal and longitudinal variations of its surface temperature. These variations, which are predominantly of spherical harmonic degrees 2 and 4, propagate to depth, imposing a long‐wavelength thermal perturbation throughout the mantle. We computed the accompanying density distribution and used it to calculate the mechanical and gravitational response of a spherical elastic shell overlying a quasi‐hydrostatic mantle. We then compared the resulting geoid and surface deformation at degrees 2 and 4 with Mercury's geoid and topography derived from the MErcury, Surface, Space ENvironment, GEochemistry, and Ranging spacecraft. More than 95% of the data can be accounted for if the thickness of the elastic lithosphere were between 110 and 180 km when the thermal anomaly was imposed. The obtained elastic thickness implies that Mercury became locked into its present 3:2 spin orbit resonance later than about 1 Gyr after planetary formation

    Aplikace anabolických steroidů s vitaminem D v časné fázi léčby polytraumatizovaných pacientů - slepá ulička?

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    PURPOSE OF THE STUDY Persistent catabolism is one of the main causes of delayed healing in polytrauma patients. The purpose of this study is to verify the effect of early administration of an anabolic steroid in combination with vitamin D on the process of bone healing in polytrauma patients. MATERIAL AND METHODS In this prospective study, the patients with a serious trauma were divided into two groups (a control group and a treatment group), with the treatment group being treated with nandrolone decanoate, an anabolic steroid in combination with vitamin D. In all the patients, bone metabolism markers and sex hormone levels (men only) were monitored through lab testing for the period of 70 days and the results of both the groups were subsequently compared. RESULTS The study included a total of 64 patients, 32 in the control group and 32 in the treatment group. The differences between the groups in gender (p = 0.387) as well as in the age of patients (p = 0.436) were statistically non -significant. There was a significant difference in the Injury Severity Score (48 in the treatment group as against 41 in the control group, p = 0.022). Even though this difference was statistically significant, it cannot be considered clinically significant since all the patients met the major trauma criteria. No positive effect of this treatment on bone metabolism parameters was established; on the very contrary, the only statistically significant changes were observed in the control group. To be specific, in levels of one of the bone formation markers, bone alkaline phosphatase on Day 7 after the injury (an increased level in the control group; p = 0.002) and in one of the bone resorption markers (bone acid phosphatase) on Day 70 after the injury (an increased level in the treatment group; p = 0.042). In the treatment group, 70 days after the injury a higher 25(OH)vitamin D level (p < 0.001) was reported and starting from Day 7 in men in the treatment group a significantly lower testosterone level and free testosterone level were observed. The level of androgenic hormones dramatically dropped in both the groups during the first days after the trauma, the dynamics of its normalization was faster in patients in the control group than in the treatment group. DISCUSSION The administration of nandrolone decanoate, an anabolic steroid, in combination with vitamin D did not produce the expected effect, i.e. an improvement in bone healing markers in polytrauma patients. One would expect that in polytrauma patients with a bone fracture or fractures during bone healing higher levels of all the markers of bone resorption as well as bone formation will persist. Similar increases in bone metabolism levels, however, were observed also in patients with injuries in other somatic regions. This indicates the importance of bone tissue involvement in the overall response of the organism to polytrauma. A faster normalization of the levels of testosterone, dihydrotestosterone and free testosterone in the control group compared to the treatment group corresponds with the supplemental effect of anabolic steroids and reduced production of these hormones as a feedback to hypothalamic-pituitary-adrenal axis. CONCLUSIONS In the follow-up period, the positive effect of anabolic steroid and vitamin D administration on bone metabolism in polytrauma patients was not confirmed.Web of Science88318317

    Permeability of the Blood-Brain Barrier and Transport of Nanobodies Across the Blood-Brain Barrier

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    The presence of a blood-brain barrier (BBB) and a blood-cerebrospinal fluid barrier presents animmense challenge for effective delivery of therapeutics to the central nervous system. Many potential drugs, which are effective at their site of action, have failed due to the lack of distribution in sufficient quantity to the central nervous system (CNS). In consequence, many diseases of the central nervous system remain undertreated. Antibodies, IgG for example, are difficult to deliver to the CNS due to their size (~155 kDa), physico-chemical properties and the presence of Fc receptor on the blood-brain barrier. Smaller antibodies, like the recently developed nanobodies, may overcome the obstacle of the BBB and enter into the CNS. The nanobodies are the smallest available antigen-binding fragments harbouring the full antigenbinding capacity of conventional antibodies. They represent a new generation of therapeutics with exceptional properties, such as: recognition of unique epitopes, target specificity, high affinity, high solubility, high stability and high expression yields in cost-effective recombinant production. Their ability to permeate across the BBBmakes thema promising alternative for central nervous system disease therapeutics. In this review, we have systematically presented different aspects of the BBB, drug delivery mechanisms employed to cross the BBB, and finally nanobodies — a potential therapeutic molecule against neuroinfections

    Crossing the Blood-Brain Barrier by Neuroinvasive Pathogens

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    The penetration of the blood-brain barrier (BBB) and invasion of the central nervous system (CNS) are important steps for all neuroinvasive pathogens. All of the ways of pathogens passing through the BBB are still unclear. Among known pathways, pathogen traversal can occur paracellularly, transcellularly or using a “Trojan horse” mechanism. The first step of translocation across the BBB is the interactions of the pathogen’s ligands with the receptors of the host brain cells. Lyme disease, the most common vector-borne disease in the temperate zones of Europe and North America, are caused by Borreliella species (former Borrelia burgdorferi sensu lato) that affects the peripheral and the CNS. In this review, we have presented various pathogen interactions with endothelial cells, which allow the disruption of the BBB so that the pathogens can pass across the BBB

    The Role of Meningococcal Porin B in Protein-Protein Interactions with Host Cells

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    Neisseria meningitidis is a Gram-negative diplococcus responsible for bacterial meningitis and fatal sepsis. Ligand-receptor interactions are one of the main steps in the development of neuroinvasion. Porin B (PorB), neisserial outer membrane protein (ligand), binds to host receptors and triggers many cell signalling cascades allowing the meningococcus to damage the host cells or induce immune cells responses via the TLR2-dependent mechanisms. In this paper, we present a brief review of the structure and function of PorB

    Contribution of Pili of S. Pneumoniae in the Onset of Meningitis

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    Bacterial meningitis is a devastating worldwide disease. Half of the survivors of meningitis remain with permanent neurological sequelae. The pathogenesis of meningitis is based on a complex host-pathogen interaction. Streptococcus pneumoniae is a life-threatening neuroinvasive pathogen that asymptomatically colonizes the upper respiratory tract. Adherence of pneumococci to the host epithelium is a prerequisite in the onset of streptococcal infections; such adherence is favored by the formation of bacterial pili. In this article, we will describe the pneumococcal pili and its contribution to the onset of meningitis

    Mercury's low-degree geoid and topography controlled by insolation-driven elastic deformation

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    Mercury experiences an uneven insolation that leads to significant latitudinal and longitudinal variations of its surface temperature. These variations, which are predominantly of spherical harmonic degrees 2 and 4, propagate to depth, imposing a long-wavelength thermal perturbation throughout the mantle. We computed the accompanying density distribution and used it to calculate the mechanical and gravitational response of a spherical elastic shell overlying a quasi-hydrostatic mantle. We then compared the resulting geoid and surface deformation at degrees 2 and 4 with Mercury's geoid and topography derived from the MErcury, Surface, Space ENvironment, GEochemistry, and Ranging spacecraft. More than 95% of the data can be accounted for if the thickness of the elastic lithosphere were between 110 and 180 km when the thermal anomaly was imposed. The obtained elastic thickness implies that Mercury became locked into its present 3:2 spin orbit resonance later than about 1 Gyr after planetary formation
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