Daptomycin nonsusceptibility in Staphylococcus aureus with reduced vancomycin susceptibility is independent of alterations in MprF

A previous study documented the presence of mutations in mprF that accompanied the loss of daptomycin susceptibility among Staphylococcus aureus isolates following exposure to the drug. An association between the development of glycopeptide-intermediate S. aureus and daptomycin nonsusceptibility has also been recently described. We report that among three clinical S. aureus isolates which developed vancomycin heteroresistance, as well as daptomycin nonsusceptibility despite a lack of exposure to this drug, there were no mutations resulting in amino acid substitutions in MprF.     

In vitro activity of SK&F 104662, a new glycopeptide antibiotic.

The in vitro activity of SK&F 104662, a new glycopeptide antibiotic, against gram-positive bacteria was evaluated. Activity was comparable to those of teicoplanin and vancomycin against most organisms. SK&F 104662 inhibited diphtheroids at concentrations of less than or equal to 0.5 microgram/ml. Addition of human serum to the test medium lowered the inhibitory activity of this glycopeptide against some organisms by as much as eightfold.     

Elevated Concentrations of Neurofilament Light Chain in the Cerebrospinal Fluid of Bipolar Disorder Patients

Bipolar disorder (BD) is characterized by mood swings between manic and depressive states. The etiology and pathogenesis of BD is unclear, but many of the affected cognitive domains, as well as neuroanatomical abnormalities, resemble symptoms and signs of small vessel disease. In small vessel disease, cerebrospinal fluid (CSF) markers reflecting damages in different cell types and subcellular structures of the brain have been established. Hence, we hypothesized that CSF markers related to small vessel disease may also be applicable as biomarkers for BD. To investigate this hypothesis, we sampled CSF from 133 patients with BD and 86 healthy controls. The concentrations of neurofilament light chain (NF-L), myelin basic protein (MBP), S100B, and heart-type fatty acid binding protein (H-FABP) were measured in CSF and analyzed in relation to diagnosis, clinical characteristics, and ongoing medications. Hereby we found an elevation of the marker of subcortical axonal damage, NF-L, in bipolar subjects. We also identified positive associations between NF-L and treatment with atypical antipsychotics, MBP and lamotrigine, and H-FABP and lithium. These findings indicate axonal damage as an underlying neuropathological component of bipolar disorder, although the clinical value of elevated NF-L remains to be validated in follow-up studies. The associations between current medications and CSF brain injury markers might aid in the understanding of both therapeutic and adverse effects of these drugs.     

Characterization of the effects of cultured vascular cells on the activation of blood coagulation

The coagulant properties of intact bovine vascular cells (aortic endothelial and smooth muscle cells) and human vascular cells (cutaneous and foreskin microvascular cells, umbilical venous endothelium) grown in vitro were studied. Compared to nonvascular cells (fibroblasts, corneal endothelial cells, fetal lung or intestinal mucosal cells), vascular cells had little procoagulant activity. Radioimmunologic measurement of thrombin in recalcified plasma demonstrated markedly lower concentrations of thrombin in the presence of vascular endothelial and smooth muscle cells compared to corneal endothelial and fetal lung cells. The low thrombin concentrations were not a consequence of thrombin binding to the vascular cells nor were they due to accelerated thrombin inactivation by antithrombin-III or alpha 2-macroglobulin. Neither vascular cells nor the nonvascular cells promoted contact activation of plasma as measured by a sensitive specific assay for kallikrein. Studies with intact cell monolayers and purified factors VIIa and X indicated that while nonvascular cells express tissue factor activity, vascular cells do not exhibit this property. These data suggest that the nonthrombogenic nature of intact vascular cells is due to their failure to initiate contact activation and to express tissue factor activity. In addition, the primary difference in coagulant potential between vascular cells and nonvascular cells is the lack of tissue factor expression by the vascular cells.     

Anemia of chronic disease is the more frequent type of anemia seen in patients with chronic idiopathic neutropenia of adults

This study describes the frequency and the type of anemia seen in patients with nonimmune chronic idiopathic neutropenia of adults (NI-CINA). We found that NI-CINA patients had low hemoglobin levels and increased serum concentrations of erythropoietin (EPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). The hemoglobin levels correlated positively with the number of circulating neutrophils and inversely with the levels of EPO and TNF-alpha but not of IL-1beta. Anemia, defined as the reduction of the hemoglobin below 12.0 g/dl for women and 13.3 g/dl for men, was found in 23 out of 148 patients studied, a proportion of 15.5%. Two of the anemic patients had iron deficiency anemia (8.7%), 11 had anemia of chronic disease (ACD; 47.8%) presenting with normal or slightly reduced erythrocytic indices, low serum iron, and increased serum ferritin, and the remaining ten had anemia of undefined pathogenesis (AUP; 43.5%) with normal or slightly decreased erythrocytic indices, serum iron ranging from 43 to 88 microg/dl, and ferritin values ranging from 12 to 50 ng/ml. We conclude that ACD is the more frequent type of anemia seen in patients with NI-CINA, and that pro-inflammatory cytokines, notably TNF-alpha, may be involved in the pathogenesis of both ACD and AUP, given that serum levels of the cytokine were significantly increased and that the EPO response to anemia was blunted in these patients. These findings further support our previously reported suggestion for the possible existence, in NI-CINA patients, of an unrecognized low-grade chronic inflammatory process that may be involved in the pathogenesis of the disorder.     

Response to 2'-deoxycoformycin after failure of interferon-alpha in nonsplenectomized patients with hairy cell leukemia

Two patients with hairy cell leukemia with massive splenomegaly and severe pancytopenia were treated with recombinant alpha-A interferon (IFN-alpha-2a). There was no significant response to a trial of IFN- alpha-2a (11 and 20 weeks) with respect to blood counts or spleen size. Subsequent treatment with 2'-deoxycoformycin (dCF) for 8 consecutive weeks (4 mg/m2/wk) resulted in normalization of spleen size and a normalization of peripheral blood counts and bone marrow in one patient. The second patient demonstrated a reduction in spleen size and improved blood counts following 9 weeks of dCF therapy but eventually became refractory. This demonstrates that dCF is non-cross-resistant with interferon and confirms the efficacy of dCF in nonsplenectomized patients.     

Septal Aperture of the Humerus: Etiology and Frequency Rates in Two European Populations

Analysis of the septal aperture was conducted on two documented European populations. Collections from the National Museum of Natural History Lisbon, Portugal, and University of Athens, Greece, were used for the study. Both collections are modern and documented for sex and age. The Portuguese sample comprises 297 individuals (149 males and 148 females) between the ages of 18 and 88. A septal aperture was observed in 50 individuals resulting in a frequency of 16.83%. The Greek sample comprises 117 individuals (68 males and 49 females) between the ages of 20 and 65. Twenty-five septal apertures were observed, giving a frequency of 21.37%. Both populations had high frequencies which exceeded those observed in European countries in previous studies. Sex analysis shows that both samples confirm that septal apertures are more common in females. The Portuguese sample also supports that septal apertures are more common in the left humerus; however, the Greek sample had a higher frequency of bilateral cases. Measurements of the Portuguese sample were taken to determine whether robusticity correlates with presence of septal apertures. These measurements concluded that there was no difference in robusticity with presence or absence of a septal aperture, challenging previous studies. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:1821–1830, 2020. © 2019 American Association for Anatomy     

Antimicrobial Activities of Skincare Preparations from Plant Extracts

In this study, Tithonia diversifolia Helms. (A Gray), Aloe secundiflora (Miller) and Azadirachta indica (A. Juss) plant extracts were used to make herbal soaps while Thevetia peruviana (Schum) seed oil was used to make a herbal lotion for skincare. The soaps were tested for the growth inhibition of Escherichia coli, and Candida albicans. The lotion was evaluated against Staphylococcus aureus and E.coli. Although Tithonia diversifolia soap exhibited the highest inhibitory effect on the test bacterial strains, it had the least inhibition against C. albicans. Results from this study indicated that the ‘Tithonia diversifolia’ soap would have superior skin protection against the tested bacteria but would offer the least skin protection against C. albicans. The herbal lotion inhibited S. aureus and E. coli in a concentration dependent manner, however, the inhibitory effect was more pronounced on S. aureus.