Area Of Necrotic Tissue Research Articles

Ischemia/Reperfusion Accelerates the Outgrowth of Hepatic Micrometastases in a Highly Standardized Murine Model *

Mortality in colorectal cancer is associated with the development of liver metastases. Surgical removal of these tumors is the only hope for cure, but recurrence is common. During liver surgery, ischemia/reperfusion (I/R) often occurs as a result of hemorrhage or vascular clamping. Although the adverse effects of I/R on postoperative liver function are well documented, the influence of I/R on the outgrowth of residual micrometastases is unknown. We used a highly standardized mouse model of partial hepatic I/R to study the effects of I/R on the outgrowth of preestablished colorectal micrometastases. Five days following intrasplenic injection of C26 colon carcinoma cells, the vascular structures of the left lobe were clamped for 45 minutes under hemodynamically stable conditions. Tissue glutathione, plasma liver enzymes, hepatocellular necrosis, and tumor growth were assessed over time. I/R caused oxidative stress and early liver tissue damage. The outgrowth of micrometastases in occluded liver lobes was accelerated five- to sixfold compared with nonoccluded lobes and was associated with areas of necrotic liver tissue surrounded by inflammatory cells and apoptotic hepatocytes. Accelerated tumor growth and tissue necrosis were completely prevented by occluding blood flow intermittently. In contrast, ischemic preconditioning or treatment with the antioxidants alpha-tocopherol or ascorbic acid failed to protect against late tissue necrosis and tumor growth, although early hepatocellular damage was largely prevented by these methods. In conclusion, I/R is a strong stimulus of recurrent intrahepatic tumor growth. Measures to prevent I/R-induced late tissue necrosis cross-protect against this phenomenon.

Acceleration of the healing process and myocardial regeneration may be important as a mechanism of improvement of cardiac function and remodeling by postinfarction granulocyte colony-stimulating factor treatment.

We investigated whether the improvement of cardiac function and remodeling after myocardial infarction (MI) by granulocyte colony-stimulating factor (G-CSF) relates to acceleration of the healing process, in addition to myocardial regeneration. In a 30-minute coronary occlusion and reperfusion rabbit model, saline (S) or 10 microg x kg(-1) x d(-1) of human recombinant G-CSF (G) was injected subcutaneously from 1 to 5 days after MI. Smaller left ventricular (LV) dimension, increased LV ejection fraction, and thicker infarct-LV wall were seen in G at 3 months after MI. At 2, 7, and 14 days and 3 months after MI, necrotic tissue areas were 14.2+/-1.5/13.4+/-1.1, 0.4+/-0.1/1.8+/-0.5*, 0/0, and 0/0 mm2 x slice(-1) x kg(-1), granulation areas 0/0, 4.0+/-0.7/8.5+/-1.0*, 3.9+/-0.8/5.7+/-0.7,* and 0/0 mm2 x slice(-1) x kg(-1), and scar areas 0/0, 0/0, 0/0, and 4.2+/-0.5/7.9+/-0.9* mm2 x slice(-1) x kg(-1) in G and S, respectively (*P<0.05, G versus S). Clear increases of macrophages and of matrix metalloproteinases (MMP) 1 and 9 were seen in G at 7 days after MI. This suggests that G accelerates absorption of necrotic tissues via increase of macrophages and reduces granulation and scar tissues via expression of MMPs. Meanwhile, surviving myocardial tissue areas within the risk areas were significantly increased in G despite there being no difference in LV weight, LV wall area, or cardiomyocyte size between G and S. Confocal microscopy revealed significant increases of cardiomyocytes with positive 3,3,3',3'-tetramethylindocarbocyanine perchlorate and positive troponin I in G, suggesting enhanced myocardial regeneration by G. The acceleration of the healing process and myocardial regeneration may play an important role for the beneficial effect of post-MI G-CSF treatment.

Changes in the periodontal ligament after experimental tooth movement using high and low continuous forces in beagle dogs.

The aim of this study was to evaluate histological changes in the periodontal structures of beagle dogs after using high and low continuous forces during experimental tooth movement. An orthodontic appliance was placed on the second premolar and the first molar by exerting a continuous and constant reciprocal force of 25 cN on one side and 300 cN on the other side of the mandible. Tooth movement was recorded weekly. Dogs were sacrificed after one, four, 20, 40, and 80 days for histological evaluation. Hematoxylin and eosin (HE) staining was used for tissue survey, staining for alkaline phosphatase as a marker was used for active osteoblasts, and tartrate-resistant acid phosphatase staining was used for osteoclasts. After 24 hours, the remodeling process had already started at the pressure and tension side, and in some samples hyalinization was found. In contrast to earlier studies, hyalinization was found throughout the entire experimental period, both in molars and in premolars. In the periodontal ligament of some teeth, small patches of hyalinization were found at the pressure side, mostly located buccally or lingually of the mesiodistal plane, whereas others showed large areas of necrotic tissue. It is concluded that hyalinization limits tooth movement, but there is no relationship with the force level.

The interaction between epiphytic algae, a parasitic fungus and Sphagnum as affected by N and P

We report the effects of fertilisation with N and P on the infection of Sphagnum by its fungal parasite Lyophyllum palustre, the expansion of epiphytic algae and the interaction between the latter two from 1998 to 2001. We added 40 kg N ha−1 yr−1 or 3 kg P ha−1 yr−1 in a full factorial design at 4 field sites. In a greenhouse experiment we reinoculated Sphagnum to verify the identity of the fungus and its necrotic effect on Sphagnum. Lyophyllum palustre was responsible for the necrosis of Sphagnum in our experiments. Adding N induced complete necrosis of Sphagnum cuspidatum by L. palustre, whereas adding P decreased the area of necrotic tissue. Disease severity was related to the N concentration in the Sphagnum capitula. In Sphagnum magellanicum and S. papillosum, infection with L. palustre resulted in defoliation of stem sections. Adding N stimulated the expansion of algae at all sites, reducing the volume of photosynthetic tissue in Sphagnum. The density of the film of algae in the treatments receiving N was a function of the frequency of defoliated Sphagnum stems.We conclude that infection with parasitic fungi and, in humid environments, the expansion of epiphytic algae, may aggravate the impact of increased N deposition or of other ecosystem disturbances that affect nutrient availability.

Neutrophils do not contribute to local tissue damage, but play a key role in skeletal muscle regeneration, in mice injected with Bothrops asper snake venom.

Local tissue damage induced by crotaline snake venoms includes edema, myonecrosis, hemorrhage, and an inflammatory response associated with a prominent cellular infiltrate. The role of neutrophils in the local tissue damage induced by Bothrops asper snake venom and by myotoxin I, a phospholipase A2 isolated from this venom, was investigated. Male Swiss mice were pretreated with either an antimouse granulocyte rat monoclonal immunoglobulin G (IgG) antibody or with isotype-matched control antibody. No significant differences in these local effects were observed between mice pretreated with antigranulocyte antibodies and those receiving control IgG. Moreover, myotoxicity induced by B. asper myotoxin I was similar in neutrophil-depleted and control mice. The role of neutrophils in the process of skeletal muscle regeneration was also assessed. Muscle regeneration was assessed by quantifying the muscle levels of creatine kinase and by morphometric histological analysis of the area comprised by regenerating cells in damaged regions of skeletal muscle. Mice depleted of neutrophils and then injected with B. asper venom showed a more deficient regenerative response than mice pretreated with control IgG. Moreover, a drastic difference in the regenerative response was observed in mice injected with myotoxin I, because animals pretreated with control IgG showed a successful regeneration, whereas those depleted of neutrophils had abundant areas of necrotic tissue that had not been removed 7 days after injection, associated with reduced contents of creatine kinase. It is concluded that (1) neutrophils do not play a significant role in the acute local pathological alterations induced by the venom of B. asper, and (2) neutrophils play a prominent role in the process of skeletal muscle regeneration after injection of B. asper venom and myotoxin I, probably related to the phagocytosis of necrotic material and the recruitment of other inflammatory cells, two events directly associated with a successful muscle regenerative response.

Local Delivery of IL-1α Polymeric Microspheres for the Immunotherapy of an Experimental Fibrosarcoma

The immunotherapeutic effects of interleukin-1α (IL-1α) encapsulated within 1–5 μm-diameter poly (D, L-lactide) microspheres and delivered intratumorally into fibrosarcoma-bearing mice were investigated. Such microspheres are avidly taken up by macrophages, and directing IL-1α into these cells may activate them to participate in antitumor responses in vivo. Treating of tumor-bearing mice with IL-1α microspheres has increased their survival rate, as compared with control mice, untreated or treated with microspheres containing bovine serum albumin (BSA). In 20% of the IL-1α-treated mice, a complete tumor regression was observed. The timing of treatment with IL-1α microspheres was crucial; optimal survival and regression rates were observed in mice treated 24 hr postinjection of the tumor cells. Administration of three doses of IL-1α microspheres on days 1, 8, and 15 postinjection of tumor cells resulted in longer survival rates. Histopathology studies on regressed tumors revealed extensive areas of tumor cell degeneration and necrotic tissue surrounded by a large number of inflammatory cells. A similar picture was observed when IL-1α microspheres were administered into the footpad of control mice, whereas the tissue reaction to BSA microspheres was much milder. Thus, it appears that tumor regression is mainly due to the antitumor effects of IL-1α. Further studies are being aimed at increasing the immunotherapeutic efficiency of microspheric IL-1α, used as a single treatment or in combination with other treatment modalities.

Allixin accumulation with long-term storage of garlic.

Extremely high accumulation of allxiin, a phytoalexin derived from garlic, was observed in necrotic tissue areas after long-term storage. The allixin produced recrystallized on the surface of the garlic clove. The amount of allixin produced in raw garlic with necrotic tissue areas was 1400 ng/mg wet garlic, which exceeds the minimum exhibitory concentration of allixin. After approximately 2 years of storage, amount of allixin accumulated reached slightly less than 1% of the dry weight of garlic cloves.

Pulpal and periapical reaction to formocresol and depulpin® in the rat teeth

One fifth dilution of formocresol is usually used for pulpotomy of the primary teeth and emergency pulpotomy of the permanent teeth. However the use of formaldehyde has been subjected to criticism because it may be absorbed into the blood stream and become distributed systemically, it nay also alter the pulp tissue rendering it immunologically active, and have carcinogenic potential. Recently Depulpin(VoCo., Germany) gains popularity as a devitalizing agent during root canal therapy in spite of high concentration of 49 % paraformaldehyde because it facilitate devitalization of pulp and make root canal therapy easier But there have been not enough publications about the reaction of pulp and periapical tissue caused by Depulpin. This study was performed to evaluate the histological changes in pulp and periapical tissue of rats after pulpotomy using formocresol and Depulpin and to elucidate the toxic effects of these agents. Thirty six Sprague-Dawley rats were anesthetized by intraperitoneal injection of ketamine Maxillary first molar teeth were used for pulpotomy with formocresol and Depulpin. Rats were sacrificed after 2 days, 4 days, 1 week, 2 weeks, 3 weeks and 4 weeks respectively. Specimens were histologically observed by light microscope changes in pulp and periapical tissue. The obtained results were as follows. 1. Formocresol group A zone of fixed tissue. in which odontoblasts could clearly be defined, was present directly underneath the pulpotomy dressing in almost all teeth of this group. This was followed by an area of necrotic tissue which resembled dried out fibrous tissue with no cellular detail except some pyknotic nuclei. In the specimens of after 2 days, 4 days, 1 week, 2 weeks in which vital tissue was present, it was separated from the fibrous area by a zone of inflammation. In the specimens of after 3 weeks and after 4 weeks, inflammatory infiltrate was in the periodontal ligament adjacent to the apical foramina of the teeth. 2. Depulpin group The area of necrotic tissue which had no cells and fibers, was present adjacent to the dressing. This was followed by dried out fibrous tissue with no cellular details except some pyknotic nuclei, A short stump of vital pulp with odontoblasts was present at the end of the canal after 2 days. Inflammatory infiltrate was in the periodontal ligament after 4 days and after 1week. Severe root resolution and necrosis of periapical tissue opposite the root resorption site were defined after 2 weeks and after 3 weeks. Periapical lesion which consist of necrotic tissue surrounded by a fibrous connective wall, was found after 4 weeks. The results indicated that Depulpin can cause more adverse reaction to the dental pulp and periapical tissue than formocresol, and further studies are needed for its clinical use with safety.

Tissue Effects of Bronchoscopic Electrocautery

To study tissue effects of bronchoscopic electrocautery (BE). In six patients with non-small cell lung cancer, a BE procedure was performed immediately before surgery. After patients were placed on ventilation, normal mucosa on different carinae was treated with a cautery probe (2-mm(2) surface area) at a power setting of 30 W with a variable time of application of 1 to 5 s. Bronchoscopic appearance of the treated area was documented photographically, and histologic changes of the bronchial wall were examined. Bronchoscopy unit of a university hospital. BE resulted bronchoscopically in whitening of the bronchial mucosa with crater-shaped lesions. After longer duration of BE application, deeper craters with more profound charring were seen. Histologic changes of the lesions showed craters containing a variable amount of necrotic tissue. In one case, thin subsegmental carinae were coagulated and measurements could not be performed. In the remaining five cases, microscopic findings revealed 0.2 +/- 0.1-mm necrosis after 1 s; 0.4 +/- 0.2-mm necrosis after 2 s; 0.9 +/- 0.5-mm necrosis after 3 s; and 1.9 +/- 0.8-mm necrosis after 5 s. A variable degree of tissue damage surrounding the necrotic tissue area was found. In one case, cartilage damage appeared after 3 s of coagulation, and extensive damage of the underlying cartilage was seen in four cases after 5 s of application. Superficial damage was obtained by short duration of BE (< or = 2 s), and longer duration of coagulation (3 s or 5 s) caused damage to the underlying cartilage. Bronchoscopic appearance after endobronchial electrocautery corresponded with the histologic changes.

The Cell Death Regulatory Protein Bak Is Expressed in Endothelial Cells in Inflamed Tissues and Is Induced by IFN-γ in Vitro

In the present report, we examined the endothelial expression of the anti- and pro-apoptotic proteins Bcl-2 and Bak in situ and in vitro. Endothelial cells (EC) in regular tissue of the bowel and the skin were essentially negative for both Bcl-2 and Bak. In contrast, EC within the walls of fistulas and abscesses in these organs stained distinctly for Bak, but remained Bcl-2-negative. In tissue culture both unstimulated human dermal microvascular endothelial cells (HDMEC) and human umbilical vein endothelial cells (HUVEC) expressed Bcl-2 and Bak constitutively. Exposure of EC to 200–1000 IU IFN-γ downregulated Bcl-2 but upregulated Bak. This opposing regulation of Bcl-2 and Bak in vitro and the expression of Bak in EC adjacent to necrotic tissue areas suggests that this pro-apoptotic protein may play a decisive role in regulation of EC survival in vivo.

Antitumor Effects of .BETA.-Subunit from Egg White Ovomucin on Xenografted Sarcoma-180 Cells in Mice.

The intraperioneal administration of β-subunit prepared from egg white ovomucin was found to suppress the growth of subcutaneously xenografted sarcoma-180 cells in mice and cure the tumor. In the present system, β-subunit (5 mg/kg of body weight) was injected to mice daily for 19 days after the 10th day when tumors had grown to 7 mm in diameter. The light and electron microscopic appearances of tumor portions on day 28 showed that β-subunit-treated tumor cells were in the states of degenerated and necrotic cells, and massive accumulations of neutrophils, macrophages and lymphocytes were found at the margin of the degenerated and necrotic tumor tissue area. These findings suggested that β-subunit brought about the regression of tumor, probably by activating the immune system.

The plasminogen activator/plasmin system is up-regulated after acute necrotizing pancreatitis in human beings

Background: Proteolysis and formation of new extracellular matrix components are important mechanisms in tissue remodeling and repair. In this study we analyzed the expression and distribution of the urokinase plasminogen activator (uPA), its membrane receptor (urokinase plasminogen activator receptor [uPAR]), and its inhibitor (plasminogen activator inhibitor-1 [PAI-1]) in acute necrotizing pancreatitis in human beings. In addition, we studied the concomitant expression of transforming growth factor–beta-1 (TGF-β 1), which is activated by uPA from its precursor and is a potent regulator and stimulator of formation of extracellular matrix. Methods: With immunohistochemistry and Northern blot analysis, the expression and cellular distribution of uPA, uPAR, PAI-1, and TGF-β 1 were determined in 12 normal pancreata obtained from organ donors and 12 pancreatic tissues obtained from patients undergoing operation because of complications of acute necrotizing pancreatitis. Results: Northern blot analysis showed enhanced expression of uPA, uPAR, and PAI-1 in eight of 12, seven of 12, and nine of 12 necrotizing pancreatitis samples, respectively, compared with normal control samples. In addition, increased TGF-β 1 mRNA expression was present in eight of 12 necrotizing pancreatitis samples. In contrast, amylase mRNA expression was markedly decreased in the samples of acute necrotizing pancreatitis. Immunohistochemistry revealed elevated uPA, uPAR, and PAI-1 immunoreactivity in the remaining acinar and ductal cells adjacent to the necrotic tissue areas. In contrast, acinar and ductal cells that were located farther from pancreatic necrosis exhibited less uPA and uPAR immunoreactivity. A similar staining pattern in samples of necrotizing pancreatitis was found for TGF-β 1. Conclusions: Up-regulation of uPA and uPAR, which activate proteolysis, might create a milieu that enhances lysis and removal of pancreatic necrosis. The increase in TGF-β 1 might result from the enhanced catalytic conversion of its precursors by uPA, which subsequently might stimulate formation of extracellular matrix, formation of granulation tissue, and fibrosis. (Surgery 1998;124:79-86.)

Are Breast Implants Anticarcinogenic? A 14-Year Follow-Up of the Los Angeles Study

Endothelins are well-known vasoconstrictor peptides produced by vascular endothelial cells that have been reported to have a fundamental role in regulation of the systemic blood circulation. Plasma levels of endothelins are increased by burn injury, which also causes thrombosis and occlusion of vessels in the dermis as well as a vascular response in the adjacent uninjured dermis. Diminished blood flow leads to progressive ischemia and necrosis of the dermis beneath and around the burn (zone of stasis). If blood flow could be restored in this zone, secondary tissue damage would be minimized. In this study we examined the effects of a new nonselective endothelin receptor antagonist, TAK-044 (Takeda Chemical Industries, Ltd., Osaka, Japan), on burn trauma in rats. Fifty male Sprague-Dawley rats weighing an average of 450 gm were burned with a brass probe that produced a row of three burns 10 x 30 mm in size and two intervening unburned areas 5 x 30 mm in size. Rats were divided into five groups of 10 animals. Four groups received 0.01, 0.1, 1 or 10 mg/kg of TAK-044 via the dorsal vein of the penis immediately after burn trauma, while the control group received the same volume of saline. Skin blood flow was measured with a laser-Doppler flowmeter, and the development of edema and the area of necrotic tissue also were determined. Inhibition of endothelin activity by TAK-044 after burn injury improved microvascular perfusion in the zone of stasis and prevented the progression of tissue damage in this zone. This supports the role of endothelins in the progression of burn injury in the zone of stasis. TAK-044 was most effective in preventing progressive burn damage at a dose of 1 mg/kg. The extent of necrosis and edema was reduced significantly, and blood flow in the zone of stasis was increased in the treated rats.

Laser ablation-induced changes in the prostate: findings at endorectal MR imaging with histologic correlation.

To correlate laser ablation-induced changes in the prostate as depicted at endorectal magnetic resonance (MR) imaging with results at histologic examination. In eight patients with prostate carcinoma, visually guided laser ablation was performed during lymphadenectomy. Radical prostate resection was performed 4-9 days (mean, 6.9 days) after ablation in seven patients and at 70 days in one patient. The study protocol consisted of (a) endorectal T2-weighted fast spin-echo imaging, (b) dynamic T1-weighted spoiled gradient-echo imaging prior to and after injection of contrast material, and (c) gadolinium-enhanced T1-weighted spin-echo imaging. Imaging findings were correlated with macroscopic and histologic findings. Histologic examination revealed periurethral necrosis with a marginal zone that consisted of partially necrotic tissue, dilated vessels, and hemorrhagic areas. Considerable interindividual difference was observed in the extent of morphologic alterations (area, 0-18.0 cm3). Gadolinium-enhanced images were best suited for assessment of laser ablation-induced changes. The correlation between the volume of altered tissue measured on MR images and in macroscopic specimens was excellent (r2 = .96). MR imaging helped monitor changes induced with laser ablation (which differed greatly among individuals). MR monitoring may thus be useful in patients with obstructive benign prostatic hyperplasia after laser ablation.

Reduction of progressive burn injury by a stable prostaglandin I 2 analogue, beraprost sodium (Procylin): an experimental study in rats

Beraprost sodium is a chemically stable prostaglandin I 2 analogue with antiplatelet and vasodilator actions. Burn injury causes thrombosis and vessel occlusion by increasing the blood viscosity and by thermal damage to the vascular network in the dermis. A vascular response also occurs in the uninjured dermis surrounding the site of injury. Diminished blood flow and spreading tissue oedema lead to progressive ischaemia and necrosis around the burn site (zone of stasis), with the final necrotic tissue area being larger than the initial one. If blood flow could be restored in the zone of stasis, secondary tissue damage would be minimized. In this study, we examined the effects of a prostaglandin I 2 analogue, beraprost sodium (Procylin, Kaken Pharmaceutical Company, Tokyo, Japan) on burn injury in rats. Twenty male Sprague-Dawley rats weighing an average of 450 g were burned with a comb-shaped brass probe that produced a row of three burns measuring 10 × 30 mm each and two intervening unburned areas measuring 5 × 30 mm each. The rats were divided into two groups of 10 animals. One group received 0.015 mg of beraprost sodium intraperitoneally immediately after burn injury, while the control group received the same volume of saline. Skin blood flow was measured with a laser Doppler flowmeter, and the development of oedema as well as the area of necrotic tissue were also determined. The extent of skin necrosis and oedema were significantly reduced in the beraprost sodium-treated rats, and blood flow in the zone of stasis was increased. These findings demonstrate that prostaglandin I 2 plays an important role in burn injury and that beraprost sodium can reduce secondary necrosis in the zone of stasis.

Skin and extremity loss in meningococcal septicaemia treated in a burn unit

Meningococcal septicaemia is a severe systemic illness which has an overall mortality of 15 per cent. It differs from meningoccocal meningitis in clinical presentation, treatment, complications and prognosis. Skin and extremity loss are particular problems seen in meningococcal septicaemia. As critical care improves more patients are being seen with these complications. We report two patients in which these complications are demonstrated. Both patients underwent multiple autogenic and allogenic skin grafting procedures for skin loss. Apparently necrotic extremities were initially treated conservatively, with good results. The total area of necrotic tissue reduced dramatically with this treatment. Despite this, however, one patient required a Syme amputation, in the other, two toes on the affected foot separated painlessly at the metatarsophalangeal joint. We also discuss some of the pathophsyiology behind skin necrosis. A popular view at present is that endotoxin from the cell wall of Neisseria meningiditis initiates the release of vasoactive cytokines by the host. High levels of interleukin-1 and interleukin-6 have been associated with a greater likelihood of fatality.

Circulatory models in assessment of cardiac enzyme release in dogs.

Cardiac ischemia causes interstitial leakage of cellular enzymes followed by release of these enzymes into plasma. Quantitative interpretation of these data requires a specific circulatory model, and the performance of such models was investigated. Plasma activities of cardiac enzymes were measured for increasingly abrupt forms of ischemic heart injury in the dog: 1) permanent ligation of the left anterior descending coronary artery (LAD); 2) reperfusion after 2 h of ligation of the LAD; and 3) calcium-free perfusion of the LAD during 10 min (calcium-paradox injury). Release into plasma of a rapidly (41%/h) and a slowly (2.2%/h) catabolized enzyme was calculated from the plasma activities, using a detailed circulatory model with compartments for heart, plasma, muscle, skin, and viscera. The time course of cellular enzyme leakage into interstitial space in the heart was calculated from release into plasma and a range of reported values for transendothelial permeability. Simplification to one- and two-compartment models introduced, respectively, 10 and 2% error in calculated cumulative release. Considering the other sources of error, this implies adequate performance of the two-compartment model. Protein washout from the heart is strongly influenced by expansion of interstitial protein space with dead myocyte volume and depends on the microheterogeneity of necrotic tissue areas. Accelerated release of enzymes into plasma after reperfusion reflects accelerated cellular leakage rather than enhanced washout.

Phagocytosis of ?/A4 amyloid fibrils of the neuritic neocortical plaques

Immunocytochemistry using monoclonal antibodies to beta/A4 protein was applied to study the macrophages involved in the removal of amyloid deposits. The material examined included necrotic brain tissue areas with abundant amyloid deposits collected from 32 autopsy cases. The beta/A4-immunoreactive products were found in numerous macrophages, appearing as early as 24 h after the onset of stroke. Immunogold electron microscope studies allowed us to localize the reaction product to the secondary lysosomes. Our study clearly demonstrates the differences between macrophages engaged in amyloid removal and microglial cells associated with amyloid deposits, which according to previous observations contain beta/A4 material within endoplasmic reticular channels.

Muscle Toxicity of Diatrizoate and Iohexol in Rabbits

The potential tissue irritating effect of diatrizoate and iohexol was studied by injecting the contrast media into the right longissimus dorsi muscle of rabbits. The left muscle served as control. The animals were sacrificed 3 days after the injection, at which time muscle tissue was examined for macroscopic changes and loss of the muscle enzyme creatine kinase (CK) from the injection site was determined. An irregular area of necrotic muscle tissue and a hemorrhage was found at the injection site in rabbits given diatrizoate, whereas iohexol only caused hemorrhage. The local loss of CK activity following diatrizoate (0.64 g muscle tissue) was statistically significantly greater than following iohexol (0.18 g muscle tissue). It is concluded that this model seems to be useful for identification of the irritating potential of contrast media. It is also concluded that diatrizoate caused more damage to the local muscle tissue than iohexol.

Social stress induces structural and functional alterations of phagocytes in rainbow trout ( Oncorhynchus mykiss)

Stress induced by social conflict in rainbow trout is known to result in physiological and haematological alterations as well as immune suppression. Based on these findings we sought to determine whether structure and function of the phagocytes in subordinate fish respond to the stressful situation. Phagocytes are essentially involved in the immune defence of teleosts. Histological and ultrastructural studies of haemopoietic pronephros tissue have shown that under stress, potential phagocytes (histiocytes, reticulum cells, endothelial cells, and neutrophils) become activated. They show marked hypertrophy, increased pseudopod formation and enhanced autophagocytosis. Erythrophagocytosis is particularly conspicuous suggesting some impairment of the red blood cell vitality. In vivo and in vitro tests using yeast cells also indicate an average increase in the phagocytosis rate in the subordinate fish. However, a considerable percentage of the phagocytes show signs of degeneration. They disintegrate, thereby forming necrotic tissue areas.