I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Methods in Enzymology.

Renin-angiotensin system: biochemistry and mechanisms of action.

https://www.gastrojournal.org/article/0016-5085(81)90648-X/pdf

Superoxide radicals in feline intestinal ischemia

The administration of glucocorticosteroids results in a wide range of effects on inflammatory and immunologically mediated disease processes. Glucocorticosteroids cause neutrophilic leukocytosis together with eosinopenia, monocytopenia, and lymphocytopenia. A principal mechanism whereby corticosteroids suppress inflammation is their impeding the access of neutrophils and monocytes to an inflammatory site. Granulocyte function is relatively refractory, whereas monocyte-macrophage function seems to be particularly sensitive to corticosteroids. Corticosteroid administration causes a transient lymphocytopenia of all detectable lymphocyte subpopulations, particularly the recirculating thymus-derived lymphocyte. The mechanism of this lymphocytopenia is probably a redistribution of circulating cells to other body compartments. There is considerable disagreement about the direct effects of corticosteroid administration on human lymphocyte function. The corticosteroid regimen should be adjusted to attain maximal therapeutic benefit with minimal adverse side effects. Often, alternate-day dosage regimens effectively maintain disease remission with minimization or lack of Cushingoid and infectious complications.

Glucocorticosteroid Therapy: Mechanisms of Action and Clinical Considerations

Previous studies have demonstrated the presence of myocardial depression in clinical and experimental septic shock. This depression is associated with the presence of a circulating myocardial depressant substance with physical characteristics consistent with cytokines. The present study utilized an in vitro myocardial cell assay to examine the role of various human recombinant cytokines, including tumor necrosis factor (TNF)alpha and interleukin (IL)1beta, in depression of cardiac myocyte contractile function induced by serum from humans with septic shock. The extent and velocity of electrically paced rat cardiac myocytes in tissue culture was quantified by a closed loop video tracking system. Individually, TNF-alpha and IL-1beta each caused significant concentration-dependent depression of maximum extent and peak velocity of myocyte shortening in vitro. In combination, TNF-alpha and IL-1beta induced depression of myocardial cell contractility at substantially lower concentrations consistent with a synergistic effect. Using immunoabsorption, removal of both TNF-alpha and IL-1beta (but not either alone) from the serum of five patients with acute septic shock and marked reversible myocardial depression resulted in elimination of serum myocardial depressant activity. IL-2, -4, -6, -8, -10, and interferon gamma failed to cause significant cardiac myocyte depression over a wide range of concentrations. These data demonstrate that TNF-alpha and IL-1beta cause depression of myocardial cell contraction in vitro and suggest that these two cytokines act synergistically to cause sepsis-associated myocardial depression in humans.

https://rupress.org/jem/article-pdf/183/3/949/1108067/949.pdf

Tumor necrosis factor alpha and interleukin 1beta are responsible for in vitro myocardial cell depression induced by human septic shock serum.

Cats subjected to coronary artery occlusion were used to study the effect of methylprednisolone on the release of lysosomal acid hydrolases and creatine phosphokinase (CPK) from ischemic myocardial tissue. Plasma CPK activity was increased significantly 2 hours after occlusion and increased eightfold 5 hours after ligation in vehicle-treated cats. Intravenous administration of methylprednisolone (30 mg/kg) 30 minutes before or 60 minutes after occlusion significantly limited the increases in plasma CPK activity to values only slightly greater than those observed in sham-operated cats. Plasma activities of the lysosomal hydrolases, β-glucuronidase and cathepsin D, were comparable in all groups of cats and did not change during the 5-hour observation period. Nevertheless, cathepsin D and β-glucuronidase activities were reduced 41% and 33%, respectively, in the ischemic portion of the myocardium of untreated cats subjected to coronary artery ligation. The CPK activity of the ischemic myocardium was reduced 43% in these cats. Pre- or posttreatment of cats with methylprednisolone prevented the decline in CPK and lysosomal hydrolase activity of ischemic myocardium. These data indicate that lysosomal disruption is a consequence of myocardial ischemia and that pre- or posttreatment with methylprednisolone prevents the leakage of myocardial lysosomal and cellular enzymes. Moreover, the methylprednisolone-induced stabilization of myocardial membranes appears to be related to the ability of glucocorticoid to limit infarct size following myocardial ischemia.

Protective Action of Methylprednisolone on the Myocardium during Experimental Myocardial Ischemia in the Cat

Splanchnic arterial occlusion (SAO) for 2 hours followed by release of the occlusion in cats produced a lethal shock state characterized by cardiovascular collapse. Release of the occlusion resulted in a 45% fall in mean arterial blood pressure within 15 minutes; postrelease survival of these animals was 46 minutes. The plasma of cats with SAO shock exhibited a 3- to 4-fold increase in activities of the lysosomal enzymes β-glucuronidase and cathepsin, accompanied by accumulation of a myocardial depressant factor. Plasma from cats treated with methylprednisolone (20 mg/kg) prior to occlusion did not have significant levels of myocardial depressant factor nor significant increases in plasma lysosomal enzyme activity. Furthermore, the fall in mean arterial blood pressure in steroid-treated animals was significantly smaller when the occlusion was released and postrelease survival time was significantly longer. Pancreatic lysosomes from cats with SAO exhibited a marked increase in fragility as indicated by a reduction in total lysosomal enzyme activity and an increase in the percent of free enzyme activity, compared to lysosomes from cats with sham SAO or steroid-treated cats. These data indicate that the biochemical and hemodynamic alterations present in SAO-induced shock may be related to the disruption of pancreatic lysosomes and that glucocorticoids can markedly alter the course of this shock, possibly by decreasing the sensitivity of pancreatic lysosomes to splanchnic ischemia.

Allan M. Lefer

Papers

Protective Action of Methylprednisolone on the Myocardium during Experimental Myocardial Ischemia in the Cat

Role of Lysosomes in the Pathogenesis of Splanchnic Ischemia Shock in Cats

Characterization of a myocardial depressant factor present in hemorrhagic shock.

Presence of a myocardial depressant factor in patients in circulatory shock.

Brief Reviews: Blood-Borne Humoral Factors in the Pathophysiology of Circulatory Shock