Introduction
Catheter-related bloodstream infections very often involve the premature removal of long-term intravascular devices (LTID). The antibiotic lock therapy (ALT) represents a conservative ...approach to the treatment of uncomplicated infections of tunneled LTID when catheter removal is not a feasible option.
Case report
We present here the first reported case of tunneled LTID bloodstream infection due to a multidrug resistant
Lactobacillus rhamnosus
. The patient, who had large granular lymphocytic leukemia, was successfully treated with systemic tigecycline therapy and lock therapy.
Conclusion
Our results confirm ALT as a valid catheter-salvage strategy for the treatment of CRBSIs in clinically stable patients when catheter removal is not a feasible option, tigecycline appear to be a good option.
Aims/hypothesis
Pancreatic islet microendothelium exhibits unique features in interdependent relationship with beta cells. Gastrointestinal products of the ghrelin gene, acylated ghrelin (AG), ...unacylated ghrelin (UAG) and obestatin (Ob), and the incretin, glucagon-like peptide-1 (GLP-1), prevent apoptosis of pancreatic beta cells. We investigated whether the ghrelin gene products and the GLP-1 receptor agonist exendin-4 (Ex-4) display survival effects in human pancreatic islet microendothelial cells (MECs) exposed to chronic hyperglycaemia.
Methods
Islet MECs were cultured in high glucose concentration and treated with AG, UAG, Ob or Ex-4. Apoptosis was assessed by DNA fragmentation, Hoechst staining of the nuclei and caspase-3 activity. Western blot analyses and pharmacological inhibition of protein kinase B (Akt) and extracellular signal-related kinase (ERK)1/2 pathways, detection of intracellular cAMP levels and blockade of adenylyl cyclase (AC)/cAMP/protein kinase A (PKA) signalling were performed. Levels of NO, IL-1β and vascular endothelial growth factor (VEGF)-A in cell culture supernatant fractions were measured.
Results
Islet MECs express the ghrelin receptor GHS-R1A as well as GLP-1R. Treatment with AG, UAG, Ob and Ex-4 promoted cell survival and significantly inhibited glucose-induced apoptosis, through activation of PI3K/Akt, ERK1/2 phosphorylation and intracellular cAMP increase. Moreover, peptides upregulated B cell lymphoma 2 (BCL-2) and downregulated BCL-2-associated X protein (BAX) and CD40 ligand (CD40L) production, and significantly reduced the secretion of NO, IL-1β and VEGF-A.
Conclusions/interpretation
The ghrelin gene-derived peptides and Ex-4 exert cytoprotective effects in islet MECs. The anti-apoptotic effects involve phosphoinositide 3-kinase (PI3K)/Akt, ERK1/2 and cAMP/PKA pathways. These peptides could therefore represent a potential tool to improve islet vascularisation and, indirectly, islet cell function.
•Training increased insulin-stimulated glucose uptake in skeletal muscle, with a decrease in plasma glucose concentration.•Plasma levels of insulin and glucose were evaluated in 12 horses during an ...IV glucose tolerance test (IVGTT).•The IVGTT was performed before and 1 month after training in a swimming pool.•Compared to pre-training values, post-training area under the curve increased for plasma glucose, but not for plasma insulin.•Low-intensity prolonged swimming exercise might improve glucose metabolism in horses.
Low intensity exercise increases insulin-stimulated glucose uptake in skeletal muscle and decreases its plasma concentration. In this study, plasma insulin and glucose concentrations were evaluated 5min before and 5, 15, 25, 35, 45 and 60min after an IV bolus of glucose in 12 Thoroughbreds before and after 1 month of submaximal aquatraining exercise, monitored using heart rate and blood lactate. Plasma glucose concentrations were evaluated using a colorimetric enzymatic method, and plasma insulin concentrations with a solid-phase radioimmunoassay method. Pre-training plasma glucose concentrations at 15, 25 and 35min, area under the glucose curve and peak glucose concentration were significantly higher than post-training values (P<0.05). Baseline pre-training plasma insulin concentrations were significantly lower than in the post-training period, and plasma insulin was significantly higher at 45 and 60min in the pre-training period than the post-training period. These results indicate that aquatraining could improve insulin-glucose metabolism in horses.
Contents
Reproductive management of male donkeys employed for artificial breeding has been poorly studied. The aim of this study was to evaluate the effect of housing system, with the animals grouped ...together in a paddock or kept in individual boxes, on sexual behaviour, cortisol and testosterone concentration and seminal characteristics of adult male donkeys. The study included four Amiata donkey jacks (stallions) from which ejaculates, saliva and blood were collected during two distinct 3 weeks periods, one in the group and one in the box housing system. Time needed for semen collection was shorter when donkeys were kept in paddocks compared to when they were kept in single boxes (14:57 ± 07:27 and 20:52 ± 09:31 min, p < .05). Native semen characteristics were not influenced by housing system, while cooled preservation in an Equitainer® showed that sperm motility parameters were significantly higher during the paddock period compared to the box period. Salivary cortisol was influenced by housing system, both before and 60 min after ejaculation, being statistically higher when donkeys were housed in paddocks. On the contrary, overall and basal testosterone concentrations were significantly higher when animals were kept in boxes. In conclusion, in the present study, good quality semen could be successfully collected from donkeys irrespective of the housing system despite some differences in hormone concentrations.
Evidence for heterodimerization has recently been provided for dopamine D1 and adenosine A1 receptors as well as for dopamine D2 and somatostatin SSTR5 receptors. In this paper, we have studied the ...possibility that D2 and D3receptors interact functionally by forming receptor heterodimers. Initially, we split the two receptors at the level of the third cytoplasmic loop into two fragments. The first, containing transmembrane domains (TM) I to V and the N-terminal part of the third cytoplasmic loop, was named D2trunk or D3trunk, and the second, containing the C-terminal part of the third cytoplasmic loop, TMVI and TMVII, and the C-terminal tail, was named D2tail or D3tail. Then we defined the pharmacological profiles of the homologous (D2trunk/D2tail and D3trunk/D3tail) as well as of the heterologous (D2trunk/D3tail and D3trunk/D2tail) cotransfected receptor fragments. The pharmacological profile of the cross-cotransfected fragments was different from that of the native D2 or D3 receptors. In most cases, the D3trunk/D2tail was the one with the highest affinity for most agonists and antagonists. Moreover, we observed that all of these receptor fragments reduced the expression of the wild type dopamine D2 and D3 receptors, suggesting that D2 and D3 receptors can form complexes with these fragments and that these complexes bind 3Hnemonapride less efficiently or are not correctly targeted to the membrane. In a second set of experiments, we tested the ability of the split and the wild type receptors to inhibit adenylyl cyclase (AC) types V and VI. All of the native and split receptors inhibited AC-V and AC-VI, with the exception of D3, which was unable to inhibit AC-VI. We therefore studied the ability of D2 and D3 to interact functionally with one another to inhibit AC-VI. We found that with D2 alone, R-(+)-7-hydroxydypropylaminotetralin hydrobromide inhibited AC-VI with an IC50 of 2.05 ± 0.15 nm, while in the presence of D2 and D3 it inhibited AC-VI with an IC50 of 0.083 ± 0.011 nm. Similar results were obtained with a chimeric cyclase made from AC-V and AC-VI. Coimmunoprecipitation experiments indicate that D2 and D3 receptors are capable of physical interaction.
BACKGROUND
Endometriosis is characterized by ectopic implantation of endometrial cells, which show increased proliferation and migration. Somatostatin (SST) and its analogues inhibit normal and ...cancer cell growth and motility through the SST receptors, sst1–5. Cortistatin (CST), which displays high structural and functional homology with SST, binds all ssts, as well as MrgX2. Our objective was to investigate the gene expression of the SST/CST system and to determine the effect of SST and its analogues on platelet-derived growth factor (PDGF)-induced proliferation and motility in telomerase-immortalized human endometrial stromal cell (T HESC) line and in primary endometrial stromal cell (ESCs) isolated from human endometriotic tissues.
METHODS
Ectopic endometrial tissues were collected from women (n= 23) undergoing laparoscopic surgery for endometriosis (Stage III/IV). Gene expression was evaluated by real-time PCR, cell motility by wound healing assay, protein expression and β-actin rearrangement by immunofluorescence, cell proliferation by the Alamar blue assay and ERK1/2 and Akt phosphorylation by western blot.
RESULTS
Human endometriotic tissues, primary ESCs and T HESCs expressed SST, CST and ssts. SST, its analogues SOM230 and octreotide, as well as CST, counteracted PDGF-induced proliferation and migration in both ESCs and T HESCs. SST also inhibited vascular endothelial growth factor and metalloprotease-2 mRNA expression, and reduced basal and PDGF-induced ERK1/2 phosphorylation.
CONCLUSION
These results indicate that the SST/CST system is expressed in endometriotic tissues and cells. The inhibitory effects of SST and its analogues on PDGF-induced proliferation and motility suggest that these peptides may represent promising tools in the treatment of endometriosis.
We investigated the association between 9 polymorphisms of genes encoding hemostasis factors and myocardial infarction in a large sample of young patients chosen because they have less coronary ...atherosclerosis than older patients, and thus their disease is more likely to be related to a genetic predisposition to a prothrombotic state.
This nationwide case-control study involved 1210 patients who had survived a first myocardial infarction at an age of <45 years who underwent coronary arteriography in 125 coronary care units and 1210 healthy subjects matched for age, sex, and geographical origin. None of the 9 polymorphisms of genes encoding proteins involved in coagulation (G-455A beta-fibrinogen: OR, 1.0; CI, 0.8 to 1.2; G1691A factor V: OR, 1.1; CI, 0.6 to 2.1; G20210A factor II: OR, 1.0; CI, 0.5 to 1.9; and G10976A factor VII: OR, 1.0; CI, 0.8 to 1.3), platelet function (C807T glycoprotein Ia: OR, 1.1; CI, 0.9 to 1.3; and C1565T glycoprotein IIIa: OR, 0.9; CI, 0.8 to 1.2), fibrinolysis (G185T factor XIII: OR, 1.2; CI, 0.9 to 1.6; and 4G/5G plasminogen activator inhibitor type 1: OR, 0.9; CI, 0.7 to 1.2), or homocysteine metabolism (C677T methylenetetrahydrofolate reductase: OR, 0.9; CI, 0.8 to 1.1) were associated with an increased or decreased risk of myocardial infarction.
This study provides no evidence supporting an association between 9 polymorphisms of genes encoding proteins involved in hemostasis and the occurrence of premature myocardial infarction or protection against it.
PDF
