INTRODUCTIONIncreasing resistance in Escherichia coli and Klebsiella pneumoniae to firstline antibiotics makes therapeutic options for urinary tract infections (UTIs) challenging. This study investigated the in vitro efficacies of 6 antibiotics against multidrug resistant (MDR) uropathogens.

MATERIALS AND METHODSMinimum inhibitory concentrations to ceftibuten, cefpodoxime, fosfomycin, mecillinam, temocillin, and trimethoprim were determined against 155 MDR-isolates of E. coli and K. pneumoniae. The presence of extended-spectrum beta-lactamases (ESBL) and plasmid-borne AmpC enzymes was determined by phenotypic testing with genotyping performed by multiplex polymerase chain reaction.

RESULTSTemocillin demonstrated highest susceptibility rates for both E. coli (95%) and K. pneumoniae (95%) when breakpoints for uncomplicated UTIs were applied; however, temocillin susceptibility was substantially lower when "systemic infection" breakpoints were used. Fosfomycin demonstrated the best in vitro efficacy of the orally available agents, with 78% and 69% of E. coli and K. pneumoniae isolates susceptible, respectively. The next most effective antibiotics were ceftibuten (45%) and mecillinam (32%). ESBL and ampC genes were present in 47 (30%) and 59 (38%) isolates.

CONCLUSIONThis study demonstrated few oral therapeutic options for MDR-uropathogens, with fosfomycin demonstrating the best in vitro activity.

Amdinocillin ; pharmacology ; Anti-Bacterial Agents ; pharmacology ; Bacterial Proteins ; genetics ; Ceftizoxime ; analogs & derivatives ; pharmacology ; Cephalosporins ; pharmacology ; Drug Resistance, Multiple, Bacterial ; genetics ; Escherichia coli ; drug effects ; genetics ; Escherichia coli Infections ; microbiology ; Fosfomycin ; pharmacology ; Genotype ; Humans ; In Vitro Techniques ; Klebsiella Infections ; microbiology ; Klebsiella pneumoniae ; drug effects ; genetics ; Microbial Sensitivity Tests ; Multiplex Polymerase Chain Reaction ; Penicillins ; pharmacology ; Singapore ; Trimethoprim ; pharmacology ; Urinary Tract Infections ; microbiology ; beta-Lactamases ; genetics

OBJECTIVETo compare the curative effects of primary osteoporosis treated with heat-sensitive point moxibustion and Gaitianli (Oyster Shell and Calcium Carbonate Chewable) tablets for oral administration and explore the treatment mechanism.

METHODSSixty cases of primary osteoporosis were randomly divided into a heat-sensitive point moxibustion group (moxibustion group) and a Gaitianli tablets group (medication group), 30 cases in each group. In the moxibustion group, the heat sensitized points were searched around Zusanli (ST 36), Pishu (BL 20), Shenshu (BL 23) and Mingmen (GV 4) and treated by heat-sensitive point moxibustion; in medication group, Gaitianli tablets were taken by oral administration, 3 pills for once and 3 times a day. The curative effects, bone mineral density (BMD), alkaline phosphatase (S-AKP) and urinary calcium to creatinine ratio (U-Ca/Cr) in both groups were observed before and after treatment.

RESULTSThe total effective rate was 86.7% (26/30) in moxibustion group, superior to that of 76.7% (23/30) in medication group (P < 0.05). After treatment, the BMD of lumbar vertebrae (L2-L4) mean was improved (P < 0.05), and the S-AKP and U-Ca/Cr were reduced (all P < 0.05); in medi cation group, the indexes above were no obvious changes (all P > 0.05).

CONCLUSIONThe therapeutic effect of primary osteoporosis treated with heat-sensitive point moxibustion is superior to that with Gaitianli tablets for oral administration. The mechanism is restraining bone resorption, increasing bone strength, keeping balance of bone metabolism, in order to increase bone mineral density and improve the clinical symptoms.

Acupuncture Points ; Aged ; Alkaline Phosphatase ; blood ; Bone Density ; Calcium ; urine ; Creatinine ; urine ; Female ; Humans ; Male ; Middle Aged ; Moxibustion ; methods ; Osteoporosis ; metabolism ; therapy

Adenosine diphosphate (ADP)-ribosylation is a unique post-translational modification that regulates many biological processes, such as DNA damage repair. During DNA repair, ADP-ribosylation needs to be reversed by ADP-ribosylhydrolases. A group of ADP-ribosylhydrolases have a catalytic domain, namely the macrodomain, which is conserved in evolution from prokaryotes to humans. Not all macrodomains remove ADP-ribosylation. One set of macrodomains loses enzymatic activity and only binds to ADP-ribose (ADPR). Here, we summarize the biological functions of these macrodomains in DNA damage repair and compare the structure of enzymatically active and inactive macrodomains. Moreover, small molecular inhibitors have been developed that target macrodomains to suppress DNA damage repair and tumor growth. Macrodomain proteins are also expressed in pathogens, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, these domains may not be directly involved in DNA damage repair in the hosts or pathogens. Instead, they play key roles in pathogen replication. Thus, by targeting macrodomains it may be possible to treat pathogen-induced diseases, such as coronavirus disease 2019 (COVID-19).
ADP-Ribosylation ; COVID-19/metabolism* ; DNA Repair/physiology* ; Evolution, Molecular ; Humans ; Models, Biological ; Models, Molecular ; N-Glycosyl Hydrolases/metabolism* ; Poly(ADP-ribose) Polymerases/metabolism* ; Protein Domains ; SARS-CoV-2/pathogenicity*

Glucocorticoid (GC) steroid hormones are used to treat acute lymphoblastic leukemia (ALL) because of their pro-apoptotic effects in hematopoietic cells. However, not all leukemia cells are sensitive to GC, and no assay to stratify patients is available. In the GC-sensitive T-cell ALL cell line CEM-C7, auto-up-regulation of RNA transcripts for the glucocorticoid receptor (GR) correlates with increased apoptotic response. This study aimed to determine if a facile assay of GR transcript levels might be promising for stratifying ALL patients into hormone-sensitive and hormone-resistant populations. The GR transcript profiles of various lymphoid cell lines and 4 bone marrow samples from patients with T-cell ALL were analyzed using both an optimized branched DNA (bDNA) assay and a real-time quantitative reverse transcription-polymerase chain reaction assay. There were significant correlations between both assay platforms when measuring total GR (exon 5/6) transcripts in various cell lines and patient samples, but not for a probe set that detects a specific, low abundance GR transcript (exon 1A3). Our results suggest that the bDNA platform is reproducible and precise when measuring total GR transcripts and, with further development, may ultimately offer a simple clinical assay to aid in the prediction of GC-sensitivity in ALL patients.
Adolescent ; Antineoplastic Agents, Hormonal ; pharmacology ; Apoptosis ; drug effects ; Branched DNA Signal Amplification Assay ; methods ; Cell Line, Tumor ; Child ; Dexamethasone ; pharmacology ; Drug Resistance, Neoplasm ; Exons ; Glucocorticoids ; pharmacology ; Humans ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; metabolism ; pathology ; Receptors, Glucocorticoid ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Transcription, Genetic ; drug effects ; Up-Regulation

Adrenal Glands ; Humans ; Hyperaldosteronism ; Retrospective Studies ; Singapore