Subject(s)
Colistin , Klebsiella pneumoniae , Anti-Bacterial Agents , Carbapenems , Humans , Klebsiella Infections , beta-LactamasesABSTRACT
Available therapeutic options against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are limited because of the high level of resistance to other antimicrobial classes including polymyxins. The double-carbapenem regimen has been recently considered a possible therapeutic strategy. In the present study, we evaluated the in vitro bactericidal and synergistic activity of a double-carbapenem regimen consisting of ertapenem plus high-dose meropenem in a series of patients with healthcare-associated CR-Kp infections in whom the use of colistin was not indicated because of potential nephrotoxicity and/or resistance. In vitro synergy was evaluated using checkerboard and killing studies. A total of 15 patients were included in the study, with sepsis, severe sepsis and septic shock found in two (13.3%), five (33.3%) and one (6.7%) patients, respectively. Overall, the clinical/microbiological response was 12/15 (80%). Synergy was observed in 11/14 (78.6%) isolates using the checkerboard method whereas in killing studies 12/14 (85.7%) and 14/14 (100%) strains were synergistic and bactericidal at 24 h at concentrations of 1 × MIC MEM+1 × MIC ERT and 2 × MEM+1 × MIC ERT, respectively, with a significant decrease of log CFU/mL compared with other combinations (p <0.0001). The double-carbapenem regimen showed clinical and in vitro effectiveness in patients with CR-Kp infections.
Subject(s)
Anti-Bacterial Agents/administration & dosage , Klebsiella Infections/drug therapy , Klebsiella pneumoniae/drug effects , Sepsis/drug therapy , Thienamycins/administration & dosage , beta-Lactams/administration & dosage , Aged , Anti-Bacterial Agents/pharmacokinetics , Cross Infection/drug therapy , Cross Infection/microbiology , Dose-Response Relationship, Drug , Drug Resistance, Multiple, Bacterial/drug effects , Drug Synergism , Ertapenem , Female , Humans , Klebsiella Infections/complications , Klebsiella Infections/microbiology , Male , Meropenem , Microbial Sensitivity Tests , Middle Aged , Sepsis/microbiology , Thienamycins/pharmacology , beta-Lactams/pharmacologyABSTRACT
Many oncogenis and tumour suppressor genes found inside normal and pathological cells are fundamental for the processes of development, proliferation and tissue differentiation. The purpose of our study is to show the presence and a possible relationship of the VEGF protein during different phases of the development of human dental germ centers. After cephalometric investigation in 8 orthodontic patients with a mean age of 13 years, (4 females and 4 males), hyperdivergence of the third molars were extracted. The 40 surgical samples were tested with monoclonal human anti-VEGFs antibodies carrying out a semi-quantitative analysis to look for a positive reaction. Reaction for anti-VEGF antibodies was detected in normal embryological tissues and in microvessels near odontogenic cells. During different phases of embryologic development of the dental bud our search showed intracytoplasmatic positive immunoreactions both in the ameloblastic and odontoblastic cells. Additionally, a positive reaction was observed for the VEGF protein in the cells of the stellate reticulum and in those endothelial tissue surrounding the microvessels in all the samples examined.
Subject(s)
Tooth Germ/chemistry , Tooth Germ/embryology , Vascular Endothelial Growth Factor A/metabolism , Adolescent , Adult , Ameloblasts/metabolism , Antibodies, Monoclonal/metabolism , Blotting, Western , Child , Densitometry , Endothelium, Vascular/metabolism , Female , Humans , Image Processing, Computer-Assisted , Immunohistochemistry , Male , Neovascularization, Physiologic , Odontoblasts/metabolism , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Tooth Germ/blood supply , Tooth Germ/cytology , Vascular Endothelial Growth Factor A/geneticsABSTRACT
Progressive ageing is associated with an increment of biomolecules modified through oxidation as a result of the action of free radicals deriving from reactive oxygen species that attack biomolecules. During ageing many alterations of renal functions have been reported. Renal ageing is associated with a progressive decline of glomerular filtration, renal blood flow and augmented vascular resistance. The kidney is a very important source of inducible nitric oxide synthase (iNOS) in both epithelial and vascular structures. In this study we have investigated mRNA and protein iNOS expression and localization and nitric oxide (NO) production in young and aged rats. An increased expression of iNOS occurs in rat kidney during ageing. In the aged rat, an increase in the values of both iNOS-RNA and iNOS protein was observed through rtPCR and Western blot analysis. The activities of three isoforms of NOS were also seen. In the aged rat kidney the production of NO decreased, due to the reduction of the activities of the three NOS. This suggests that in the aged rat a progressive increase of superoxide anion does not imply an increase in the production of NO which functions as a scavenger molecule, causing oxidative stress with accumulation of reactive oxygen species (ROS).
Subject(s)
Aging/metabolism , Free Radical Scavengers/metabolism , Kidney/metabolism , Nitric Oxide/metabolism , Actins/metabolism , Animals , Blotting, Western , Citrulline/metabolism , Electrophoresis, Polyacrylamide Gel , Epithelial Cells/metabolism , Image Processing, Computer-Assisted , Male , Nitric Oxide Synthase/metabolism , Nitric Oxide Synthase Type II , Rats , Rats, Wistar , Renal Circulation/physiology , Reverse Transcriptase Polymerase Chain ReactionSubject(s)
Cell Differentiation/physiology , Gene Expression Regulation, Enzymologic/drug effects , Hypoxanthine Phosphoribosyltransferase/biosynthesis , IMP Dehydrogenase/biosynthesis , Mycophenolic Acid/pharmacology , Phosphoric Diester Hydrolases/biosynthesis , Cell Differentiation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Humans , Kinetics , Neuroblastoma , Nucleotides/metabolism , Tumor Cells, CulturedSubject(s)
Amniotic Fluid/chemistry , Fetal Diseases/diagnosis , Hypoxanthine/analysis , Xanthine/analysis , Adult , Biomarkers/analysis , Biomarkers/blood , Chromatography, High Pressure Liquid , False Positive Reactions , Female , Humans , Hypoxanthine/blood , Maternal Age , Predictive Value of Tests , Pregnancy , Pregnancy, High-Risk , Prenatal Diagnosis , Xanthine/bloodABSTRACT
Purine nucleotide degradation products have been determined by HPLC in aqueous humor obtained during cataract surgery and from plasma of 22 patients (12 women). Uric acid, cytosine, guanosine monophosphate, uracyl, guanine, adenosine, adenosine monophosphate, thymine, adenine, inosine, cyclic guanosine monophosphate, hypoxanthine and xanthine were evaluated. Uric acid and the last two were the only compounds detectable in measurable amounts in aqueous humor and in plasma of all patients. Aqueous humor xanthine levels were not significantly different from plasma; aqueous humor hypoxanthine concentrations were lower than those of xanthine and than plasma oxypurine levels. In 8 patients, treated with allopurinol, oxypurinol concentrations in aqueous humor and in plasma were comparable suggesting that oxypurines are transported through the blood-aqueous humor barrier.
