Uptake of meta-iodobenzylguanidine by bovine chromaffin granule membranes

meta-Iodobenzylguanidine, an adrenal imaging agent used for the scintigraphic detection of human pheochromocytoma, is a substrate for the monoamine uptake system of chromaffin granules. It is accumulated by bovine chromaffin granule membrane vesicles in the presence of ATP, and it can be released by an osmotic shock. The uptake is dependent upon the generation of an H+-electrochemical gradient by an ATP-dependent H+ pump since it is blocked by an H+ ionophore and since meta-iodobenzylguanidine uptake can be driven by imposing an artificial pH gradient (inside acidic) on the membrane vesicles. The transport is saturable and its Km value (2.0 microM at pH 8.0) is similar to that of noradrenaline (5.3 microM). Transport occurs through the monoamine transporter since it is blocked by the same inhibitors, tetrabenazine and reserpine, and also by the transporter substrates noradrenaline and serotonin. Noradrenaline inhibits meta-iodobenzylguanidine uptake competitively (Ki = 13 microM). In addition, meta-iodobenzylguanidine displaces dihydrotetrabenazine and reserpine from their binding sites on chromaffin granule membranes. It is thus likely that, after in vivo administration, [131I] meta-iodobenzylguanidine is ultimately stored in chromaffin granules and that it is translocated by the monoamine transporter.     

The effects of shivering on oxygen consumption and carbon dioxide production in patients rewarming from hypothermic cardiopulmonary bypass

Oxygen consumption (VO2), carbon dioxide production (VCO2), end-tidal carbon dioxide partial pressure (PETCO2), mixed venous oxygen saturation (SvO2) and haemodynamic variables were recorded every 30 min for four hours in 15 patients recovering from hypothermic cardiopulmonary bypass (CPB). All patients had been anaesthetised with fentanyl 40 micrograms.kg-1, supplemented with isoflurane, and pancuronium 0.15 mg.kg-1 for muscle relaxation. Three of the 15 patients (20 per cent) shivered, defined as intermittent or continuous, vigorous movements of chest or limb muscles. Patients who shivered had a VO2 of 159 +/- 16.4 ml.min-1.m-2 on arrival in the ICU which rose to a maximum value of 254 +/- 28.3 ml.min-1.m-2 by 150 min post-CPB. In contrast, patients who did not shiver had a significantly lower VO2 of 93.1 +/- 6.9 ml.min-1.m-2 on arrival in the ICU which rose to a maximal value of only 168 +/- 11.5 ml.min-1.m-2 by 180 min post-CPB. Maximal VO2 in both groups was reached when the nasopharyngeal temperature (NPT) was approaching normal. VCO2 paralleled the increase in VO2 in both groups. By four hours there was no significant difference between the two groups; however, the VO2 in both groups (160.5 +/- 21.3 ml.min-1.m-2 and 173.9 +/- 12.3 ml.min-1.m-2 respectively) was approximately twice values commonly measured in anaesthetized patients. Patients who shivered had a significantly higher heart rate and cardiac index and significantly lower SvO2. We conclude that the high VO2 and VCO2 associated with shivering causing increased myocardial work may be detrimental to patients who have impaired cardiac function post-coronary artery surgery (CAS).     

Ontogeny of B lymphocytes in mice. Quantification of surface membrane immunoglobulins by immunoperoxidase assay.

Surface membrane immunoglobulins (SmIg) of splenic lymphocytes were investigated by immunoperoxidase assay in newborn Swiss mice, their mothers and adult controls. The mean number of SmIg + cells in adult mice was 45-8% and the mean number of antigenic sites per positive cells was 108,500. In newborn mice during the first 7 days of life, values for both parameters were low (24-25--28-5% and 38,000-45,773 respectively) and began to rise after the 10th day to reach adult levels between the ages of 2 and 3 weeks. A peak above adult levels for the mean number of sites per cell was observed on day 21 with a subsequent drop to adult levels on day 28. Post-partum females were found to have consistently fewer sites per positive cell (69,000-86,600) during the 14 days following delivery than their adult control counterparts, though the difference was not statistically significant.     

Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers

Epigenetic therapy is emerging as a potential therapy for solid tumors. To investigate its mechanism of action, we performed integrative expression and methylation analysis of 63 cancer cell lines (breast, colorectal, and ovarian) after treatment with the DNA methyltransferase inhibitor 5-azacitidine (AZA). Gene Set Enrichment Analysis demonstrated significant enrichment for immunomodulatory pathways in all three cancers (14.4-31.3%) including interferon signaling, antigen processing and presentation, and cytokines/chemokines. Strong upregulation of cancer testis antigens was also observed. An AZA IMmune gene set (AIMs) derived from the union of these immunomodulatory pathway genes classified primary tumors from all three types into “high” and “low” AIM gene expression subsets in tumor expression data from both TCGA and GEO. Samples from selected patient biopsies showed upregulation of AIM genes after treatment with epigenetic therapy. These results point to a broad immune stimulatory role for DNA demethylating drugs in multiple cancers.     

Epidemiologic and Genomic Analysis of SARS-CoV-2 Delta Variant Superspreading Event in Nightclub,the Netherlands,June 2021

We report a severe acute respiratory syndrome coronavirus 2 superspreading event in the Netherlands after distancing rules were lifted in nightclubs, despite requiring a negative test or vaccination. This occurrence illustrates the potential for rapid dissemination of variants in largely unvaccinated populations under such conditions. We detected subsequent community transmission of this strain.     

Community-acquired methicillin-resistant Staphylococcus aureus clones circulating in Belgium from 2005 to 2009: changing epidemiology

The present study reports the evolution of the demographic characteristics and the molecular epidemiology of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) in Belgium from 2005 to 2009. Four hundred and ten CA-MRSA isolates were prospectively collected and screened for the presence of Panton–Valentin leucocidin (PVL) and toxic shock syndrome toxin 1 (TSST-1) encoding genes, while clinical information were recorded. PVL- and TSST-1-positive isolates were genotyped by pulsed-field gel electrophoresis (PFGE). Staphylococcal cassette chromosome mec (SCCmec) type, spa type and multilocus sequence type (MLST) were determined on representative isolates. One hundred and fifty-nine (39 %) isolates were PVL-positive. PVL-positive isolates were significantly more frequently isolated from skin or soft tissue than PVL-negative isolates, causing mainly subcutaneous abscesses and furuncles. Patients with PVL-positive CA-MRSA were significantly younger than patients with PVL-negative CA-MRSA. Eighty-seven percent of the PVL-positive isolates belonged to a limited number (n?=?7) of PFGE types belonging to sequence types (ST) ST80, ST8, ST30, ST5, ST152, ST338 and a new ST, a single-locus variant of ST1. A temporal evolution of the distribution of these PFGE types was observed, characterised by (1) the dissemination of the ST8-SCCmecIV arcA-positive (USA300) genotype and (2) a genetic diversification. Forty-seven (11 %) strains were TSST-1-positive, of which 65 % clustered into four PFGE types, all belonging to ST5. The epidemiology of CA-MRSA in Belgium is changing, as the rapid diffusion of the USA300 clone seems to occur, together with a clonal diversification.     

Evolución de pacientes tratados con armazones coronarios bioabsorbibles liberadores de everolimus tras su disolución completa

Introduction and objectivesLong-term outcomes of unselected patients treated with bioresorbable vascular scaffold (BVS) implantation are lacking, especially for the period after complete dissolution of the BVS. This study sought to evaluate 5-year outcomes in patients treated with BVS in routine practice.MethodsConsecutive patients who underwent implantation of everolimus-eluting BVS during routine clinical practice at 2 high-volume centres in Germany were studied. The patients were followed-up for up to 5 years. The primary endpoints of interest were the composite of death, myocardial infarction and target lesion revascularization, as well as definite scaffold thrombosis.ResultsA total of 419 patients (mean age 66.6 ± 10.9 years; 31.5% had diabetes) were included, of whom 38.9% presented with an acute coronary syndrome. Of the 527 lesions treated, 49.0% were classified as complex and 13.1% were bifurcation lesions. At 5 years, the composite clinical endpoint occurred in 33.1% of patients and definite scaffold thrombosis occurred in 4.7%. Most definite scaffold thrombosis occurred within 2 years after BVS implantation.ConclusionsIn patients treated with BVS implantation in routine clinical practice the rates of adverse clinical events at 5 years were high, including a considerable incidence of scaffold thrombosis.