Effects of amrinone on thrombin-induced platelet-derived growth factor-like protein secretion from endothelial cells

Endothelial cells (EC) secrete platelet-derived growth factor (PDGF)-like protein, which is a potent mitogen to smooth muscle and connective tissue cells. The purpose of this study was to determine if amrinone, a phosphodiesterase inhibitor, could inhibit PDGF-like protein secretion on the basis of its ability to increase cAMP. Human umbilical artery endothelial cells (HUAEC) (n = 7) were preincubated for 4 h with amrinone (10 micrograms/mL) before coincubation with thrombin (10 IU/mL) and amrinone (10 micrograms/mL) for 18 h. The supernatant was then assayed for the presence of both PDGF-like protein by using a competitive 125I-PDGF radioreceptor inhibition assay, and cAMP by using an RIA. Thrombin-induced PDGF-like protein secretion from HUAEC was significantly inhibited by amrinone (7.8 +/- 1.6 fmol/10(6) EC) when compared with thrombin alone (12.1 +/- 2.4 fmol/10(6) EC) (p less than 0.05). Amrinone alone had no effect on baseline PDGF-like protein secretion. Amrinone inhibition of thrombin-induced PDGF-like protein secretion was comparable whether amrinone was added to HUAEC 4 or 0 h before thrombin, and it was dose dependent with a maximal inhibition of 82.7% by amrinone (160 micrograms/mL). In contrast, IL-1 alpha (10 micrograms/mL) and tumor necrosis factor (100 ng/mL) induced less secretion of PDGF-like protein from HUAEC, and this secretion was not inhibited by amrinone. Amrinone (10 micrograms/mL) significantly increased secretion of cAMP from HUAEC from a baseline value of 6.4 +/- 0.4 pmol/10(6) EC to 10.6 +/- 0.1 pmol/10(6) EC (p less than 0.01). We conclude that amrinone inhibits thrombin-induced PDGF-like protein secretion from HUAEC.(ABSTRACT TRUNCATED AT 250 WORDS)     

Recurrent wheezing in relation to environmental risk factors in infancy

Clinical course and environmental factors were recorded in a prospective study of 276 unselected infants followed from birth to the age of 18 months. The study was performed with a questionnaire at the age of 6 and 12 months and a physical examination at 18 months. Fifty-nine (21%) of the children had greater than or equal to 2 episodes of wheezing before they were 18 months old. A total of 58 (21%) of the children belonged to the lowest social class V, 182 (66%) were daily exposed to passive tobacco smoking at home and/or in daycare, 164 (59%) were breastfed greater than or equal to 3 months, 192 (70%) were in daycare, 62 (22%) lived in flats and 167 (61%) were in daily contact with furred pets at home and/or in daycare. In social class V a preponderance of children were exposed to passive tobacco smoking, a majority were living in flats and a minority were breastfed greater than or equal to 3 months. Linear logistic regression analysis was used for the purpose of assessing the causal effect of environmental risk factors on the risk of recurrent episodes of wheezing before the age of 18 months. The study demonstrated that male sex and daily exposure to passive tobacco smoking were significant risk factors with estimated odds ratios 1.9 and 2.4, respectively. Maternal tobacco smoking seemed to be associated with the highest risk. There was a tendency--though not significant--indicating that breastfeeding greater than or equal to 3 months had a protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of Size, Dosage, and Surface Structure on Clearance and Tissue Distribution of Intravenous Microspheres

Intravenously injected polystyrene microspheres with functional amino groups (AP-MSs, 0.2,1.0, and 4.0 urn in diameter) were cleared from the blood very rapidly. The calculated half-lives for 0.2-, 1.0-, and 4.0-μm AP-MSs were about 55,60, and 50s; no significant differences were found with 10⁶,10⁷, and 10⁸ microspheres/rat. Loading experiments showed that the liver, spleen, lung, kidney, and heart had a very high capacity to take up AP-MSs. The AP-MSs were distributed mainly to the liver, lung, and spleen, whereas other organs contained less than 1 % of injected AP-MSs. In terms of numbers of AP-MSs per gram of tissue, the highest contents were found in spleen, liver, and lung for 0.2-, 1.0-, and 4.0-um AP-MSs, respectively. There was indication of redistribution of particles from one organ to another during the first 6 h after injection. Chondroitin sulfate A (Chon) and hyaluronic acid (Hya) adsorbed or covalently linked to AP-MSs increased uptake in the liver, with Chon AP-MSs (adsorbed or linked) showing the best effect: about 25% increase compared with unadsorbed 1-μm AP-MSs. Experiments with separated cells in vitro demonstrated that 1 um AP-MSs, intravenously injected, associated only with Kupffer cells. When the microspheres were adsorbed with Chon, there was also association with liver endothelial cells. This finding indicates that conjugation of microspheres with ligands for endothelial receptors may be a useful method for directing microspheres to specific organs, even if the receptors are not by themselves phagocytic     

Die Durchblutung handgenähter und geklammerter Colonanastomosen

Zusammenfassung In einer tierexperimentellen Studie wurde die Durchblutung nach Anlage einer handgenähten und geklammerten End-zu-End-Anastomose am Schweinedickdarm verglichen. Bei keinem der 15 Tiere trat ein Nahtleck auf. Im Bereich handgeknoteter Fäden konnten einzelne umschriebene minderdurchblutete Gebiete festgestellt werden, die am 7. und 14. postoperativen Tag deutlich sichtbar wurden, wenn die Anastomosen vermehrt vascularisiert waren. Bei den Klammernähten wurden solche Ausfälle der Gewebsdurchblutung nicht gesehen. Die intramuralen Arterien zogen unbehindert durch die B-förmig gestalteten Klammern hindurch. Ein unauffälliges Gefäßmuster und eine abgeschlossene Anastomosenheilung wurden bei den Klammernähten nach 3 Wochen und bei Handnähten nach 4 Wochen beobachtet.

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Blood supply of stapled and sutured colonic anastomoses

Summary The blood supply of end-to-end staple and suture lines in the pig colon was compared. In 15 operated animals there was no anastomotic leak. Sporadic circumscribed areas of restricted circulation could be noticed in hand-sewn anastomoses. This effect was marked on the 7th and 14th postoperative day, when vascularisation of the anastomoses was increased. Such lack of vascular supply was not seen in stapled anastomoses. The intramural arteries passed through the B-shaped staples without hindrance. An unremarkable vascular pattern and a completed healing of the anastomoses were observed after 3 weeks in staple lines and after 4 weeks in suture lines.

Herrn Prof. Dr. Dr. h.c. F. Stelzner zum 65. Geburtstag gewidmet     

Elastolytic activity of human monocytes from synovial fluid and blood of patients with arthritis. Relations to levels of interleukin 6 and soluble interleukin 2 receptor

Synovial fluid (SF) and blood from 24 patients with non-traumatic, sterile hydarthron were examined for monocyte elastolysis (M?E) and for levels of interleukin 6 (IL-6) and of soluble interleukin 2 receptor (sIL-2R). Six patients had osteoarthrosis (OA) and 18 patients had inflammatory hydarthron (IH), 10 of whom had rheumatoid arthritis (RA). Blood M?E was lower in OA than in IH, both measured as basal M?E activity and after in vitro stimulation with immune complexes and phorbol myristate acetate (PMA). SF M?E was higher than M?E in blood (p less than 0.01). This increase in SF M?E could be mimicked in vitro by prestimulation of blood M? with low levels of IC. SF IL-6 and sIL-2R were also elevated (p less than 0.01). All three parameters correlated to the degree of joint inflammation evaluated by SF leucocyte level, complement activation, blood C Reactive Protein, and to the clinical evaluation of the joint. The increase in SF M?E, IL-6 and sIL-2R in patients with IH, points to a stimulation of M? and lymphocytes in the joint.     

Bromine-76 and carbon-11 labelled NNC 13-8199, metabolically stable benzodiazepine receptor agonists as radioligands for positron emission tomography (PET)

NNC 13-8241 has recently been labelled with iodine-123 and developed as a metabolically stable benzodiazepine receptor ligand for single-photon emission computed tomography (SPECT) in monkeys and man. NNC 13-8199 is a bromo-analogue of NNC 13-8241. This partial agonist binds selectively and with subnanomolar affinity to the benzodiazepine receptors. We prepared ⁷⁶Br labelled NNC 13-8199 from the trimethyltin precursor by the chloramine-T method. Carbon-11 labelled NNC 13-8199 was synthesised by N-alkylation of the nitrogen of the amide group with [¹¹C]methyl iodide. Positron emission tomography (PET) examination with the two radioligands in monkeys demonstrated a high uptake of radioactivity in the occipital, temporal and frontal cortex. In the study with [⁷⁶Br]NNC 13-8199, the monkey brain uptake continued to increase until the time of displacement with flumazenil at 215 min after injection. For both radioligands the radioactivity in the cortical brain regions was markedly reduced after displacement with flumazenil. More than 98% of the radioactivity in monkey plasma represented unchanged radioligand 40 min after injection. The low degree of metabolism indicates that NNC 13-8199 is metabolically much more stable than hitherto developed PET radioligands for imaging of benzodiazepine receptors in the primate brain. [⁷⁶Br]NNC 13-8199 has potential as a radioligand in human PET studies using models where a slow metabolism is an advantage. Received 19 April and in revised form 10 June 1997     

New Biological and Clinical Roles for the n–6 and n–3 Fatty Acids

Four new findings of the biochemistry and biology of the essential n–6 and n–3 fatty acids have recently been demonstrated. These findings will augment current knowledge as to the role of the essential fatty acids in human health.     

The image and advocacy of public health in American caricature and cartoons from 1860 to 1900.

The decades just before and after the founding of the American Public Health Association in 1872 saw an efflorescence of political cartooning and caricature in national-circulation weeklies. Part of the political and social critique that cartoonists and their editors provided the public focused on needs or opportunities for preventing illness and accidents. This paper presents a small selection of editorial cartoons that agitated in support of public health activities over 4 decades. The goals are to illustrate several concerns that rose to national prominence in that era, to examine the kinds of imagery that newspapers and magazine editors offered their readers, and to observe how frequently the public was encouraged to see politicians and commercial interests as responsible for preventable health problems. This discussion focuses exclusively on propagandistic images, leaving aside the reportorial depictions of events in the news and the neutral illustrations of methods and machines in scientific and technical publications.