Activated mast cells increase the level of endothelin-1 mRNA in cocultured endothelial cells and degrade the secreted Peptide

Subendothelial mast cells have been implicated in the pathogenesis of allergic inflammation, in atherosclerosis, and in the regulation of vascular tone. Because endothelin-1 (ET-1) is an important regulator of vascular tone and has also been implicated in the pathogenesis of atherosclerosis, we studied the role of mast cells in the metabolism of endothelial cell-derived ET-1. In mast cell-endothelial cell cocultures, activation of the mast cells with ensuing degranulation was accompanied by the increased expression of ET-1 mRNA in the endothelial cells, yet the immunoreactive ET-1 protein in the coculture medium disappeared almost completely during the 24-hour coculture. Activation of the mast cells with the ensuing degranulation resulted in proteolytic degradation of ET-1 by the 2 neutral proteases, chymase and carboxypeptidase A, of the exocytosed mast cell granules. With synthetic ET-1 and purified mast cell granule enzymes, efficient degradation of ET-1 by chymase and carboxypeptidase A was verified. These in vitro results imply a novel role for mast cell-derived neutral proteases in ET-1 metabolism and suggest that activated subendothelial mast cells are important local regulators of ET-1 metabolism.     

Associations between mean arterial pressure during cardiopulmonary bypass and biomarkers of cerebral injury in patients undergoing cardiac surgery: secondary results from a randomized controlled trial

Open in a separate window OBJECTIVESCardiac surgery is associated with risk of cerebral injury and mean arterial pressure (MAP) during cardiopulmonary bypass (CPB) is suggested to be associated with cerebral injury. The ‘Perfusion Pressure Cerebral Infarcts’ (PPCI) trial randomized patients undergoing coronary artery bypass grafting (CABG) and/or aortic valve replacement to a MAP of 40–50 or 70–80 mmHg during CPB and found no difference in clinical or imaging outcomes between the groups. We here present PPCI trial predefined secondary end points, consisting of biomarkers of brain injury.METHODSBlood was collected from PPCI trial patients at baseline, 24 and 48 h after induction of anaesthesia and at discharge from the surgical ward. Blood was analysed for neuron-specific enolase, tau, neurofilament light and the glial marker glial fibrillary acidic protein. Linear mixed models were used to analyse differences in biomarker value changes from baseline between the 2 MAP allocation groups.RESULTSA total of 193 (98%) patients were included. We found no differences in biomarker levels over time from baseline to discharge between the 2 MAP allocation groups (P_NSE = 0.14, P_Tau = 0.46, P_NFL = 0.21, P_GFAP = 0.13) and the result did not change after adjustment for age, sex and type of surgery.CONCLUSIONSWe found no significant differences in levels of biomarkers of neurological injury in patients undergoing elective or subacute CABG and/or aortic valve replacement randomized to either a target MAP of 40–50 mmHg or a target MAP of 70–80 mmHg during CBP.     

Apolipoprotein E ε4 allele frequency is increased in Parkinson’s disease only with co-existing Alzheimer pathology

We determined the apolipoprotein E (apoE) genotype in clinically diagnosed and neuropathologically verified cases of Parkinson’s disease (PD) (n = 45), with or without Alzheimer (AD)-type changes, and compared the apoE genotype with that in healthy age-matched controls (n = 59). The PD cases were divided into two groups according to the CERAD criteria: “O + A”, with no or only uncertain histological findings of AD, and “B + C” with histological findings suggestive or indicative of AD. DNA was isolated from frozen brain samples, and the apoE genotypes were determined using polymerase chain reaction amplification and subsequent restriction analysis by HhaI enzyme. The frequency of the apoɛ4 allele (29.4%) was significantly increased in the B + C group. The odds ratio for an apoɛ4 allele in the B + C group was 2.5 as compared to controls (95% confidence interval, 1.2–5.2). In the 0 + A group, the frequency of apoɛ4 allele (13.6%) was similar to that in controls (14.4%) and the risk of an apoɛ4 allele was not increased (odds ratio 0.94). The PD cases with an apoɛ4 allele had a greater number of cortical (P = 0.02) but not nigral Lewy bodies than those without an apoɛ4 allele (P = 0.57). The results show that neuropathologically verified PD as such is not associated with increased apoɛ4 allele frequency. Received: 15 January 1998 / Revised, accepted: 24 March 1998     

Toxic acute hepatitis and hepatic fibrosis after consumption of chaparral tablets

In this report we describe a young, previously healthy woman who developed severe acute hepatitis after consumption of chaparral tablets, a commonly used herbal product. In this case, the elimination-rechallenge event and the exclusion of other possible aetiologic factors strongly supported true causality between the herbal product and the liver damage. Primary liver biopsy showed severe toxic hepatitis consistent with previous reports of chaparral-induced liver damage. Later, 6 months after the liver function tests had normalized, permanent hepatic fibrosis could still be seen.     

A multiplatform real-time polymerase chain reaction detection assay for Vibrio cholerae

We report a multiplatform real-time polymerase chain reaction methodology based on genes encoding for the regulatory toxR activator and enterotoxin A protein to determine enterotoxigenic Vibrio cholerae types from other vibrios. This assay, which was successfully validated on a collection of 87 bacterial strains, including 63 representatives of V. cholerae and 8 noncholera vibrios provides a rapid tool for detection and identification of cholera.     

Antibodies against Streptococcus pneumoniae, Haemophilus influenzae and Branhamella catarrhalis in middle ear effusion during early phase of acute otitis media

Serum type (IgG, IgM and IgA-class) and secretory type antibodies specific to Streptococcus pneumoniae (Pn), Haemophilus influenzae (Hi) and Branhamella catarrhalis (Br) were measured by enzyme-linked immunosorbent assay (ELISA) in 46 serum and 114 middle ear effusion (MEE) samples from 85 children with acute otitis media (AOM). The samples were obtained within 12 h from the onset of the ear symptoms. Serum (but not secretory) type antibodies to the infecting Pn serotype were found in 24% of the MEE samples of the patients with Pn AOM and, correspondingly, serum and/or secretory type antibodies to Hi and Br were seen in 54% and 63% of the MEE samples of the patients with Hi or Br AOM, respectively. Moreover, antibodies against bacteria other than the causative one could also be found in the MEE. The occurrence of the serum type antibodies against these bacteria in the MEE was closely correlated with their serum levels. The findings of this study indicate that during the very early phase of AOM, the MEE contains both serum type antibodies originating from the serum, and secretory antibodies of middle ear origin. Among them there are antibodies specific to the three most common bacteria causing AOM (Pn, Hi, and Br) regardless of the bacterial etiology of the AOM attack in question.     

C-reactive protein in acute otitis media

Serum C-reactive protein (CRP) levels were studied in 79 children with acute otitis media (AOM), aged from 4 months to 5 years. The CRP was less than 10 mg/l in 27 children, greater than or equal to 20 mg/l in 34, and greater than or equal to 40 mg/l in 17 children, 25 of the 41 attacks caused by S. pneumoniae or H. influenzae showed a CRP of greater than or equal to 20 mg/l and 15 CRP greater than or equal to 40 mg/l, in 38 cases without major otitis pathogens, the respective figures were 9 (p less than 0.01) and 2 (p less than 0.001). Although statistically significant correlations between otitis-related clinical parameters and CRP levels were rare, there was a tendency toward higher CRP values among those with a more severe clinical picture. All five attacks with CRP greater than or equal to 100 mg/l were bilateral, caused by major pathogens, and preceded by a respiratory infection. They also tended to have high fever and a large amount of fluid in myringotomy. However, even in these the general course of AOM and other morbidity was not different from the others.     

Serum antibodies to pneumococcal C polysaccharide in children: response to acute pneumococcal otitis media or to vaccination

Immunoglobulin class-specific antibody responses to the pneumococcal C polysaccharide (CPS) and to the capsular polysaccharides of types 3, 6A, 18C and 19F were measured by enzyme-linked immunosorbent assay in the sera of children ages 6 months to 7 years. Twenty of these children had acute otitis media caused by pneumococci of type/group 3, 6, 18 or 19, whereas 20 received an injection of 14-valent pneumococcal capsular polysaccharide vaccine. Many of the children in both groups had large concentrations of IgG and/or IgM class anti-CPS antibodies in their first serum sample. Both the infection and the vaccine elicited anti-CPS responses in all three immunoglobulin classes, most notably IgA. The pneumococcal capsular polysaccharides used as antigens in the enzyme-linked immunosorbent assay were found to contain CPS in amounts ranging from less than 1 to 30%. As a result the enzyme-linked immunosorbent assay detected both anti-type-specific and anti-CPS antibodies. After elimination of the anti-CPS, type-specific pneumococcal antibodies were found only occasionally and in low concentrations in serum samples obtained in the acute phase of otitis or before vaccination. The infection induced homologous type-specific pneumococcal antibodies to varying degrees depending on the type: regularly to type 3; and fairly regularly to type 18C polysaccharide, but seldom to type 6 or 19. The pneumococcal vaccine induced type-specific antibodies to all four types measured, but the response to type 6A was poor.