Adenosine decreases post-ischaemic cardiac TNF-alpha production: anti-inflammatory implications for preconditioning and transplantation.

Tumour necrosis factor-alpha (TNF-alpha) is an autocrine contributor to myocardial dysfunction and cardiomyocyte death in ischaemia-reperfusion injury (I/R), sepsis, chronic heart failure and cardiac allograft rejection. Cardiac resident macrophages, infiltrating leucocytes, and cardiomyocytes themselves produce TNF-alpha. Although adenosine reduces macrophage TNF-alpha production and protects myocardium against I/R, it remains unknown whether I/R induces an increase in cardiac TNF-alpha in a crystalloid-perfused model (in the absence of blood), and, whether adenosine decreases cardiac TNF-alpha and protects function after I/R. To study this, isolated rat hearts were crystalloid-perfused using the Langendorff method and subjected to I/R, with or without adenosine pretreatment. Post-ischaemic cardiac TNF-alpha (enzyme-linked immunosorbent assay and bioassay) and function were determined (Langendorff). I/R increased cardiac TNF-alpha and impaired myocardial function. Adenosine decreased cardiac TNF-alpha and improved post-ischaemic functional recovery. This study demonstrates that: first, I/R induces an increase in cardiac tissue TNF-alpha in a crystalloid-perfused model: second, adenosine decreases cardiac TNF-alpha and improves post-ischaemic myocardial function; third, decreased cardiac TNF-alpha may represent a mechanism by which adenosine protects myocardium; and fourth, adenosine-induced suppression of cardiac TNF-alpha may provide an anti-inflammatory link to preconditioning and have implications for cardiac allograft preservation.     

The juxtaglomerular apparatus in malignant hypertension of man

Summary Investigation of the behaviour of the renal Juxtaglomerular apparatus in 19 patients with malignant hypertension has shown that in kidneys fixed immediately after operation the Juxtaglomerular granulation index is twice as high as in autopsy kidneys. The formation of renin by the epitheloid cells begins with the appearance of osmiophilic substances in the region of the endoplasmic reticulum. The first stages of granule formation are small rhomboid particles in the Golgi cisternes, which aggregate to form bigger round or polymorphic granules in the Golgi area.In pathological conditions the substances synthesized may be set free and become active locally as a result of fibrinoid necrosis of the vascular wall. The rate of production is increased firstly by forcing rhe production of active agents in the preexistent epitheloid cells, secondly by transformation of the so-called bivalent cells and finally, by cell division.In accelerated hypertension the production of renin also takes place in nephrons whose glomeruli, tubules and macula densa, are damaged. There is a correlation between blood pressure elevation and the Juxtaglomerular granulation index.

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Zusammenfassung Untersuchungen über das Verhalten des juxtaglomerulären Zellkomplexes der Niere bei 19 Patienten mit maligner Hypertonie haben folgendes ergeben: In operativ gewonnenen und sofort fixierten Nieren ist der juxtaglomeruläre Granulationsindex doppelt so hoch wie in Nieren aus dem Sektionsgut. Die Reninbildung der epitheloiden Zellen beginnt mit dem Auftreten osmiophiler Substanzen im Bereich des endoplasmatischen Reticulums. Kleine rhomboide Gebilde in Golgizisternen sind Vorstufen von reifen Sekretgranula, die sich im Golgifeld zu größeren runden oder vielgestaltigen Sekrettropfen zusammenlagern.Unter pathologischen Bedingungen können infolge fibrinoider Gefäß- wandnekrosen Sekretsubstanzen lokal frei und lokal wirksam werden. Vermehrte Arbeitsleistung erfolgt zunächst durch Forcierung der Sekretproduktion in den präexistenten epitheloiden Zellen, sodann durch Transformierung sogenannter bivalenter Zellen und schließlich durch Zellneubildungen.Reninproduktion findet bei akzelerierter Hypertonie auch in solchen Nephronen statt, deren Glomerula und Tubuli samt Macula densa strukturell geschädigt sind. Es besteht eine Korrelation zwischen Höhe des Blutdruckes und Höhe des Granulationsindex.

     

Olfactory and taste sensitivity in children with cystic fibrosis.

Psychophysical experiments measured both olfactory sensitivity to 1-butanol and sodium chloride and taste sensitivity to sodium chloride in normal children and in children with cystic fibrosis. The sensitivity of the children with cystic fibrosis fell within the normal range. These results stand in contrast to those of Henkin and Powell, who found children with cystic fibrosis to be hypersensitive to both olfactory and taste stimuli. Apparent hypersensitivity to taste stimuli could have resulted from the adapting effects of the relatively high level of sodium in the saliva of children with cystic fibrosis. If the contaminating effects of saliva are removed, children with cystic fibrosis yield, on the average, a taste threshold identical to that of normal children. There appears to be no simple explanation for why Henkin and Powell found hypersensitivity to odorants. The present results indicate that, in fact, children with cystic fibrosis display a slight hyposensitivity to odorants.     

Taste and olfaction: Independence vs interaction

Twenty persons sipped and judged overall perceived magnitude, odor magnitude, and taste magnitude of various concentrations of the odorant citral, the tastants sodium chloride and sucrose, and odorant-tastant combinations. In a second experiment, the same twenty persons sniffed and judged perceived odor magnitude for the same set of stimuli. The investigation probed two primary questions: Does the apparent harmony of an olfactory-taste mixture dictate the degree of additivity in that mixture? Does harmony of the components influence the production of any taste-smell confusion? The data from both the harmonious mixture (citral and sucrose) and the dissonant mixture (citral and NaCl) imply absence of sensory inhibition or facilitation between taste and olfaction. Nevertheless, both types of mixtures led to substantial taste-smell confusion whereby olfactory stimulation evoked sensations of taste.     

Optimal detection of the progression of coronary artery disease: comparison of methods suitable for risk factor intervention trials

To assess the best method of quantitating progression of coronary disease, we studied four measurements in 114 coronary segments from 35 medically treated patients from whom angiograms were obtained 5 years apart. Only stenoses of less than 70% that were visualized in nearly identical projections on both angiograms were evaluated. Vessel edges were measured by use of catheter calibration and an automated computer algorithm yielding two "absolute dimensions" (mean and minimum diameters) and two measurements (percent stenosis and atheroma area) that required a "normal reference" diameter. The coefficient of variation for repeated segment measurements was less for mean and minimum diameter than for percent stenosis and area of atheroma. The best measure of progression of coronary disease as determined by t test comparison of different methods was the change in mean diameter over time (6.7 +/- 14.1% decrease), whether calculated on a per coronary segment or per patient basis (p less than .001). Based on this measurement and its standard deviation of progression of coronary disease in this patient subset with relatively benign disease, it is estimated that 470 patients per group would be required for an interventional study to demonstrate a 33% reduction in disease progression (207 patients for 50% reduction) at a 95% confidence level and 90% power.     

Draize rabbit eye test compatibility with eye irritation thresholds in humans: a quantitative structure-activity relationship analysis.

Draize rabbit eye test scores, as modified maximum average score (MMAS), for 68 pure bulk liquids were adjusted by the liquid-saturated vapor pressure P. These 68 adjusted scores, as log (MMAS/P), were shown to be completely equivalent to eye irritation thresholds (EIT), expressed as log (1/EIT), for 23 compounds in humans. Thus, for the first time the Draize eye test in rabbits for pure bulk liquids is shown to be perfectly compatible with eye irritation thresholds in humans. The total data set for 91 compounds was analyzed by the general solvation equation of Abraham. Values of log (MMAS/P) or log (1/EIT) could be fitted to a five-parameter equation with R2 = 0.936, SD = 0.433, AD = 0.000, and AAD = 0.340 over a range of 9.6 log units. When divided into a training set of 45 compounds, the corresponding equation could be used to predict the remaining 46 compounds in a test set with AD = -0.037 and AAD = 0.345 log units. Thus, the 91-compound equation can now be used to predict further EIT values to around 0.4 log units. It is suggested that the mechanism of action in the Draize test and in the human EIT involves passive transfer of the compound to a biophase that is quite polar, is a strong hydrogen bond base, a moderate hydrogen bond acid, and quite hydrophobic. The biophase does not resemble water or plasma, but resembles an organic solvent such as N-methylformamide.     

Live/Real Time Three‐Dimensional Transesophageal Echocardiographic Assessment of Ventricular Septal Volume and Mass before and after Myectomy in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common genetically transmitted cardiomyopathy. In patients resistant to medical management, myectomy is the surgical procedure of choice to reduce the symptoms of left ventricular outflow obstruction. Two‐dimensional transesophageal echocardiography (2DTEE) has become part of the operative procedure by decreasing the incidence of postoperative complications. However, because of the three‐dimensional geometry of left ventricular outflow tract, it is unable to comprehensively assess the location and severity of the obstruction and to provide accurate guidance during myectomy. In this study, 10 patients with HCM underwent live/real time three‐dimensional transesophageal echocardiography (3DTEE) intra‐operatively to measure the volume of the resected septum. This volume correlated well with the volume of the resected septal muscle directly obtained using a graduating cylinder containing water (r = 0.9, P < 0.000). 3DTEE may be potentially used as an adjunct to guide the surgeon in performing an adequate myectomy with a lower incidence of residual obstruction and complications such as an iatrogenic ventricular septal defect.