Background And Objectives: Selvigaltin (GB1211), an orally available small molecule galectin-3 inhibitor developed as a treatment for liver fibrosis and cirrhosis, was evaluated to assess the effect of hepatic impairment on its pharmacokinetics and safety to address regulatory requirements.
Methods: GULLIVER-2 was a Phase Ib/IIa three-part study. Parts 1 and 3 had single-dose, open-label designs assessing pharmacokinetics (plasma [total and unbound] and urine), safety, and tolerability of 100 mg oral selvigaltin in participants with moderate (Child-Pugh B, Part 1) or severe (Child-Pugh C, Part 3) hepatic impairment, compared with healthy-matched participants (n = 6 each).
Serum liver tests (serum tests) and histological assessment for T-cell-mediated rejection are essential for post-liver transplant monitoring. Liver biopsy carries a risk of complications that are preferably avoided in low-risk patients. Multiparametric magnetic resonance imaging (mpMRI) is a reliable noninvasive diagnostic method that quantifies liver disease activity and has prognostic utility.
View Article and Find Full Text PDFThe pathogenesis of multiple sclerosis (MS) suggests that, in genetically susceptible subjects, T lymphocytes undergo activation in the peripheral compartment, pass through the BBB, and cause damage in the CNS. They produce pro-inflammatory cytokines; induce cytotoxic activities in microglia and astrocytes with the accumulation of reactive oxygen species, reactive nitrogen species, and other highly reactive radicals; activate B cells and macrophages and stimulate the complement system. Inflammation and neurodegeneration are involved from the very beginning of the disease.
View Article and Find Full Text PDFMultiple sclerosis (MS) is predominantly an immune-mediated disease of the central nervous system (CNS) of unknown etiology with a possible genetic predisposition and effect of certain environmental factors. It is generally accepted that the disease begins with an autoimmune inflammatory reaction targeting oligodendrocytes followed by a rapid depletion of their regenerative capacity with subsequent permanent neurodegenerative changes and disability. Recent research highlights the central role of B lymphocytes and the corresponding IgG and IgM autoantibodies in newly forming MS lesions.
View Article and Find Full Text PDFIntroduction: The rising incidence of liver diseases is a worldwide healthcare concern. However, the therapeutic options to manage chronic inflammation and fibrosis, the processes at the basis of morbidity and mortality of liver diseases, are very limited. Galectin 3 (Gal-3) is a protein implicated in fibrosis in multiple organs.
View Article and Find Full Text PDFTherapeutic plasma exchange (TPE) is an efficient extracorporeal blood purification technique to remove circulating autoantibodies and other pathogenic substances. Its mechanism of action in immune-mediated neurological disorders includes immediate intravascular reduction of autoantibody concentration, pulsed induction of antibody redistribution, and subsequent immunomodulatory changes. Conventional TPE with 1 to 1.
View Article and Find Full Text PDFObjective: Dexamethasone could be an effective prophylactic agent for the prevention of pain flares after palliative radiotherapy (RT) for uncomplicated bone metastases. To date, there are no data on its prophylactic coanalgesic (opioid-sparing) effect after RT in patients with complicated bone metastases compared to uncomplicated ones, which is the aim of our study.
Methods: Twenty-nine American Society of Anaesthesiologists (ASA) III-IV patients, aged ≥18, treated with single-fraction 8 Gy/1 or multi-fraction 20 Gy/5 RT for painful uncomplicated bone metastases (steroid naïve patients, = 14) or complicated ones (steroid non-naïve patients, = 15), were examined retrospectively.
According to the American Academy of Neurology 2011 guidelines, there is insufficient evidence to support or refute the use of therapeutic plasma exchange (TPE) for myasthenia gravis (MG). The goal of this study was to determine whether a novel nanomembrane-based TPE could be useful in the treatment of MG. Thirty-six adult patients, MGFA 4/4B and 5, with acute MG episodes were enrolled into a single-center retrospective before-and-after study to compare a conventional treatment group ( = 24) with a nanomembrane-based TPE group ( = 12).
View Article and Find Full Text PDFThe activity concentrations of the naturally occurring radionuclides 238U, 234U and 210Po have been determined for the first time in drinking water from certain sources in Southern Bulgaria using nuclear and radiochemical methods. The results obtained for the water samples vary in the intervals 0.6-678 mBq l-1 for 238U, 1.
View Article and Find Full Text PDFJ Environ Sci Health A Tox Hazard Subst Environ Eng
September 2021
The main objective of the present study was to determine and differentiate the concentration levels, to define the probable sources of persistent organic pollutants (POPs) pollution in the atmospheric air and their seasonal variations in Bulgaria, on the high mountain peak Moussala, Rila Mountain. The study was based on the obtained results from the passive monitoring of POPs in 2014-2017. During this period, the measurements of POPs were performed with passive samplers, advanced instrumental methods analytically determined the concentrations of PAHs, and the analysis of the obtained data was performed by the multivariate statistical analysis (cluster, factor and time-series analysis).
View Article and Find Full Text PDFThe rapid advances in nuclear medicine have resulted in significant advantages for the field of oncology. The focus is on the application of radiopharmaceuticals as therapeuticals. In addition, the latest developments in cell biology (the understanding of the cell structure, function, metabolism, genetics, signaling, transformation) have given a strong scientific boost to radiation oncology.
View Article and Find Full Text PDFBackground: The rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the more aggressive subtype, nonalcoholic steatohepatitis (NASH), is a global public health concern. Left untreated, NAFLD/NASH can lead to cirrhosis, liver failure, and death. The current standard for diagnosing and staging liver disease is a liver biopsy, which is costly, invasive, and carries risk for the patient.
View Article and Find Full Text PDFExcited states in 102Rh, populated in the fusion-evaporation reaction Zr94(11B,3n)102Rh at a beam energy of 36 MeV, were studied using the Indian National Gamma Array spectrometer at Inter University Accelerator Center, New Delhi. The angular correlations and the electromagnetic character of some of the gamma-ray transitions observed were investigated in detail. A new chiral candidate sister band was found.
View Article and Find Full Text PDFTetrahedral symmetry in strongly interacting systems would establish a new class of quantum effects at subatomic scale. Excited states in 156Gd that could carry the information about the tetrahedral symmetry were populated in the 155Gd(n,γ)156Gd reaction and studied using the GAMS4/5 Bragg spectrometers at the Institut Laue-Langevin. We have identified the 5(1)- → 3(1)- transition of 131.
View Article and Find Full Text PDFIsospin symmetry breaking has been investigated in mass A=67 mirror nuclei through the experimental determination of the E1 strengths of analog electromagnetic transitions. Lifetimes of excited states have been measured in (67)Se and (67)As with the centroid shift method. Through the comparison of the B(E1) strengths of the mirror 9/2(+)-->7/2(-) transitions, the isovector and the isoscalar components of the electromagnetic transition amplitude were extracted.
View Article and Find Full Text PDFBackground: Sapphyrin analogues and related porphyrin-like species have attracted attention as anticancer agents due to their selective localization in various cancers, including hematologic malignancies, relative to surrounding tissues. Sapphyrins are electron affinic compounds that generate high yields of singlet oxygen formation. Although initially explored in the context of photodynamic therapy, sapphyrins have intrinsic anticancer activity that is independent of their photosensitizing properties.
View Article and Find Full Text PDFPhys Rev Lett
February 2006
Exited states in 134Pr were populated in the fusion-evaporation reaction 119Sn(19F,4n)134Pr. Recoil distance Doppler-shift and Doppler-shift attenuation measurements using the Euroball spectrometer, in conjunction with the inner Bismuth Germanate ball and the Cologne plunger, were performed at beam energies of 87 MeV and 83 MeV, respectively. Reduced transition probabilities in 134Pr are compared to the predictions of the two quasiparticle + triaxial rotor and interacting boson fermion-fermion models.
View Article and Find Full Text PDFFollowing the heavy-ion fusion-evaporation reaction 32S+24Mg at 95 MeV beam energy the lifetimes of analogue states in the T(z)=+/-1/2 A=51 mirror nuclei 51Fe and 51Mn have been measured using the Cologne plunger device coupled to the GASP gamma-ray spectrometer. The deduced B(E2;27/2(-)-->23/2(-)) values afford a unique opportunity to probe isoscalar and isovector polarization charges and to derive effective proton and neutron charges, epsilon(p) and epsilon(n), in the fp shell. A comparison between the experimental results and several different large-scale shell-model calculations yields epsilon(p) approximately 1.
View Article and Find Full Text PDF993 surgical site infection aerobic pathogens are isolated over a six-year period (I.1994-I.2000) by the Microbiology Laboratory at University Hospital "Tzaritza Joana".
View Article and Find Full Text PDFPhys Rev Lett
September 2001
Gamma rays from the N = Z-2 nucleus (50)Fe have been observed, establishing the rotational ground state band up to the state J(pi) = 11+ at 6.994 MeV excitation energy. The experimental Coulomb energy differences, obtained by comparison with the isobaric analog states in its mirror (50)Cr, confirm the qualitative interpretation of the backbending patterns in terms of successive alignments of proton and neutron pairs.
View Article and Find Full Text PDFKhirurgiia (Sofiia)
January 1999
Over a one-year period (Nov. 1996-Nov. 1997), a total of 154 patients are admitted on an emergency basis, with deferred emergency and for routine treatment in the Clinic of Emergency Surgery.
View Article and Find Full Text PDFOver a one-year period (November 1996 to November 1997), in the Emergency Surgery Clinic perioperative parenteral antibiotic prophylaxis during colorectal operations is performed in a series of 32 patients, admitted on an emergency and deferred urgency basis, or for routine operative treatment. Of them 30 present malignant processes involving colon and rectum, and two--inflammatory diseases. All patients receive single i.
View Article and Find Full Text PDFIn the period 1990 through 1995, one-hundred patients operated for acute abdomen or admitted on a routine basis, presenting evidence of anaerobic infection, undergo treatment in the clinic of emergency surgery. Septic shock develops in 10/100 patients (10 per cent). In six of the latter the outcome is fatal--three with infection caused by spore-forming anaerobes (gas gangrene of the inguinal region--of Fournier, and anterior abdominal wall--anus praeternaturalis--two), and three with infection caused by non-spore-forming anaerobes (mixed anaerobic-aerobic infection).
View Article and Find Full Text PDFKhirurgiia (Sofiia)
November 1993
Experience is recorded with lincomycin treatment of 59 patients with acute surgical abdomen. The primary anaerobic flora was eradicated in 86 per cent of the patients. For the very good therapeutic results essential was the early instituted adequate antibiotic therapy in adequate dose and for adequate length of time.
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