glycogen and Necrosis

Topics: Glycogen; Histocytochemistry; Humans; Lipid Metabolism; Microscopy, Electron; Mitochondria, Heart; Myocardial Infarction; Myocardium; Necrosis; Time Factors

Topics: Acidosis; Adenosine Triphosphate; Allosteric Site; Anaerobiosis; Animals; Arteries; Carbohydrate Metabolism; Cell Survival; Coronary Vessels; Creatine Kinase; Enzyme Activation; Fatty Acids; Glucose; Glycogen; Glycolysis; Heart; Hypoxia; Ischemia; Lactates; Mitochondria, Muscle; Myocardium; Necrosis; Oxidation-Reduction; Oxidative Phosphorylation; Phosphofructokinase-1; Phosphorylases; Veins

Topics: Acute Disease; Biopsy; Cholestasis; Cytoplasm; Feces; Glycogen; Hepatitis A; Hepatitis B; Hepatitis B Antigens; Humans; Inclusion Bodies, Viral; Inflammation; Jaundice; Kupffer Cells; Liver; Lysosomes; Microscopy, Electron; Mitochondria, Liver; Necrosis; Ribosomes

Topics: Animals; Chlordan; DDT; Endoplasmic Reticulum; Ethanol; Glycogen; Lipid Metabolism; Liver; Liver Diseases; Necrosis; Nikethamide; Phenobarbital; Protein Biosynthesis; Rats; Tolbutamide

Topics: Adolescent; Biopsy; Child; Child, Preschool; Cytoplasm; Diet Therapy; Electromyography; Female; Glycogen; Humans; Infant; Lipid Metabolism; Male; Mitochondria, Muscle; Motor Neurons; Muscles; Muscular Atrophy; Muscular Diseases; Muscular Dystrophies; Necrosis; Nervous System Diseases; Obesity; Obesity Hypoventilation Syndrome

Copper nanoparticles are widely utilized in a variety of applications, including metal catalysts, semiconductors, heat transfer fluids in machine tools, and even in antibacterial medications. Forty mature healthy Westar rats were utilized in the current investigation and grouped randomly into four groups (n = 10 rats/group). Group I (G1) was kept as a control group, but G2, G3, and G4 were intraperitoneally injected with CuO NPs with a dose (5 mg, 10 mg, 25 mg/kg body weight/day) respectively for 9 days. Rats were sacrificed; then, the livers and kidneys were dissected and subjected to histopathological and immunohistochemical examination. Our findings of G2 and G3 revealed mild to moderate degenerative changes within the hepatic parenchyma, moderate blood vessel congestions, glycogen depletion, hemosiderosis, and microvesicular steatosis (fatty changes within the hepatocytes). In addition, at the level of kidney, our examination clarified moderate degenerations of the renal corpuscles and renal tubules with moderate swelling and congestions of the glomerulus with moderate vacuolations in the renal tubules lining epithelium. On the other hand, increasing the dose of CuO NPs, the toxicity became more obvious, where the liver of G4 revealed severe necrosis of hepatocytes with completely disorganizations of the hepatic rays, loss of the hepatic architectures, severe steatosis, severe hemosiderosis, sinusoidal dilatations with congestions, as well as severe fibrous tissue proliferation with anti-inflammatory cell infiltrations specially around portal triad with hyperplasia of bile duct. Meanwhile in kidney, G4 clarified severe necrosis and atrophy of the renal corpuscles with severe damage of Bowman's capsule leading to completely disorganization and loss of normal renal cortex architectures, severe congestion of the glomerulus, severe necrosis of the renal tubules with damage and sloughing for its lining epithelium, and severe hemorrhage between renal tubules. In addition, severe and diffuse caspase 3 immunoreactivity were observed within the hepatic and renal tissues of G4. The present investigation was concluded that the CuO NPs have a potential toxicological effect on the hepatic and renal tissues that may affect their functions.-->.

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Caspase 3; Copper; Glycogen; Hemosiderosis; Liver; Male; Metal Nanoparticles; Nanoparticles; Necrosis; Oxides; Rats

Deltamethrin (DTM) is a synthetic pyrethroid widely used in the cultivation and management of several crops due to its insecticidal action. Application to crops of pyrethroids such as DTM can result in the exposure of water and fruit consumed by fruit bats having a high pyrethroid content which may be harmful. Therefore the objective of this study was to evaluate the effects of short-term oral exposure of the fruit-eating bats (Artibeus lituratus) to two concentrations of DTM (0.02 and 0.04 mg/kg of papaya) on histopathology of the intestine, liver and kidney. The intestine of the animals exposed to both concentrations showed inflammatory infiltrate, degeneration, necrosis and goblet cell hyperplasia as the most frequent pathologies. Besides, the acid mucins showed an increase in the frequency of non-viable cells. The liver showed hepatocyte vacuolizatio and nuclear enlargement, as well as inflammatory infiltrate and steatosis. The kidneys of the exposed animals showed and inflammatory infiltrate, benign nephrosclerosis, vacuolization and necrosis. Also, DTM reduced nitric oxide synthesis, decreased glomerular diameter and increased glycogen percentage in the proximal tubules. Our results suggest that acute exposure to DTM at low concentrations has the potential to induce pronounced histopathological changes in vital organs, such as intestine, liver and kidney of fruit-eating bats.

Topics: Animals; Chiroptera; Glycogen; Mucins; Necrosis; Nitric Oxide; Nitriles; Pyrethrins; Water

Non-alcoholic steatohepatitis (NASH) is a chronic disease characterized by inflammation, steatosis, and liver fibrosis. The liver is particularly affected by alterations in lipid metabolism. Our aim was to evaluate the effect of β-hydroxyphosphocarnitine (β-HPC) on NASH induced in rats.. NASH was characterized by elevated triglycerides, elevated liver damage enzymes, and the presence of necrosis, inflammation, steatosis, and fibrosis. Significant amounts of glycogen were found, along with α-SMA positive cells in fibrosis areas. The over-expression of SREBP-1 in cytoplasm and nuclei was evident. Animals with NASH treated with β-HPC showed a significant reduction in inflammation, necrosis, and glycogen content in the liver. A reduction in α-SMA and SREBP-1 immunopositive cells correlated with a significant reduction in the degree of fibrosis and steatosis found in liver tissue. β-HPC reduced the levels of ALP and GGT, and significantly reduced triglyceride levels. Animals treated with β-HPC did not show any alterations in liver enzyme function.. Our research shows that β-HPC can improve liver function and morphology in the case of NASH induced in rats, suggesting β-HPC could be potentially used in the treatment of NASH.

Topics: Animals; Carnitine; Cholesterol; Diet, High-Fat; Disease Models, Animal; Fructose; Glucose; Glycogen; Inflammation; Liver; Liver Cirrhosis; Necrosis; Non-alcoholic Fatty Liver Disease; Organophosphates; Rats; Rats, Wistar; Sterol Regulatory Element Binding Protein 1; Triglycerides

We investigated the role of secondhand smoke (SHS) exposure, independently of diet, in the development of chronic liver disease. Standard diet-fed mice were exposed to SHS (5 h/day, 5 days/week for 4 months). Genome-wide gene expression analysis, together with molecular pathways and gene network analyses, and histological examination for lipid accumulation, inflammation, fibrosis, and glycogen deposition were performed on the liver of SHS-exposed mice and controls, upon termination of exposure and after one-month recovery in clean air. Aberrantly expressed transcripts were found in the liver of SHS-exposed mice both pre- and post-recovery in clean air (

Topics: Animals; Apoptosis; Cluster Analysis; Collagen; Endoplasmic Reticulum; Glycogen; Lipid Metabolism; Liver; Male; Mice; Mice, Inbred C57BL; Necrosis; Non-alcoholic Fatty Liver Disease; Phenotype; Principal Component Analysis; Tobacco Smoke Pollution; Transcriptome

The purpose of this study was to determine the effects of single and combined administrations of deoxynivalenol (DON) and zearalenone (ZEN) on the histology and ultrastructure of pig liver. The study was performed on immature gilts, which were divided into four equal groups. Animals in the experimental groups received DON at a dose of 12 μg/kg body weight (BW) per day, ZEN at 40 μg/kg BW per day, or a mixture of DON (12 μg/kg BW per day) and ZEN (40 μg/kg BW). The control group received vehicle. The animals were killed after 1, 3, and 6 weeks of experiment. Treatment with mycotoxins resulted in several changes in liver histology and ultrastructure, including: (1) an increase in the thickness of the perilobular connective tissue and its penetration to the lobules in gilts receiving DON and DON + ZEN; (2) an increase in the total microscopic liver score (histology activity index (HAI)) in pigs receiving DON and DON + ZEN; (3) dilatation of hepatic sinusoids in pigs receiving ZEN, DON and DON + ZEN; (4) temporary changes in glycogen content in all experimental groups; (5) an increase in iron accumulation in the hepatocytes of gilts treated with ZEN and DON + ZEN; (6) changes in endoplasmic reticulum organization in the hepatocytes of pigs receiving toxins; (7) changes in morphology of Browicz-Kupffer cells after treatment with ZEN, DON, and DON + ZEN. The results show that low doses of mycotoxins used in the present study, even when applied for a short period, affected liver morphology.

Topics: Animals; Chemical and Drug Induced Liver Injury; Female; Glycogen; Iron; Liver; Necrosis; Sus scrofa; Trichothecenes; Zearalenone

There is an extensive literature establishing, validating, and quantifying a wide range of responses of fishes to fasting. Our study complements this work by comparing fed and unfed treatments of hatchery-raised Delta Smelt (Hypomesus transpacificus)-an imperiled fish that is endemic to the San Francisco Estuary and its tributaries in California, USA-across a diverse suite of endpoints over a two-month time series. The experiment was conducted at 15.9°C, and individuals were sampled at 12 time points as starvation became increasingly severe. We found that hepatosomatic index and condition factor were relatively sensitive to starvation, becoming significantly depressed at Day 4 and 7, respectively. Histological analysis of liver showed elevated cytoplasmic inclusion bodies at Day 7, followed by increased glycogen depletion, single cell necrosis, and hydropic vacuolar degeneration at Day 14, 21, and 28, respectively. Of four antioxidants measured, glutathione decreased at Day 4, superoxide dismutase increased at Day 14, catalase increased at Day 56, and glutathione peroxidase was not affected by starvation. The net result was a ~2-fold increase in lipid peroxidation (malondialdehyde) in fasted fish that was highly inconsistent through time. RNA to DNA ratio and triglycerides in muscle were relatively insensitive to starvation, only consistently decreasing with fasting after mortality began increasing in the 'No Feeding' treatment, at Day 21. Together, these results suggest that Delta Smelt mobilize hepatic energy stores far more rapidly than lipids in muscle when subjected to fasting, leading to rapid atrophy of liver and the development of cytoplasmic inclusion bodies-possibly autophagosomes-in hepatocytes.

Topics: Animals; Catalase; Glutathione; Glycogen; Inclusion Bodies; Liver; Malondialdehyde; Muscles; Necrosis; Osmeriformes; Starvation; Superoxide Dismutase; Time Factors

This study was designed to investigate whether the mice treated with triptolide (TP) could disrupt the liver immune homeostasis, resulting in the inability of the liver to eliminate the harmful response induced by lipopolysaccharide (LPS). In addition, we explored whether apoptosis and necroptosis played a critical role in the progression of the hepatotoxicity induced by TP-LPS co-treatment.. Female C57BL/6 mice were continuously administrated with two different doses of TP (250 μg/kg and 500 μg/kg) intragastrically for 7 days. Subsequently, a single dose of LPS (0.1 mg/kg) was injected intraperitoneally to testify whether the liver possesses the normal immune function to detoxicate the exogenous pathogen's stimulation. To prove the involvement of apoptosis and necroptosis in the liver damage induced by TP-LPS co-treatment, apoptosis inhibitor Z-VAD-FMK (FMK) and necroptosis inhibitor necrostatin (Nec-1) were applied before the stimulation of LPS to diminish the apoptosis and necroptosis respectively.. TP or LPS alone did not induce significant liver damage. However, compared with TP or LPS treated mice, TP-LPS co-treatment mice showed obvious hepatotoxicity with a remarkable elevation of serum ALT and AST accompanied by abnormal bile acid metabolism, a depletion of liver glycogen storage, aberrant glucose metabolism, an up-regulation of inflammatory cell infiltration, and an increase of apoptosis and necroptosis. Intraperitoneal injection of FMK or Nec-1 could counteract the toxic reactions induced by TP-LPS co-treatment.. TP could disrupt the immune response, resulting in hypersensitivity of the liver upon LPS stimulation, ultimately leading to abnormal liver function and cell death. Additionally, apoptosis and necroptosis played a vital role in the development of liver damage induced by TP-LPS co-treatment.

Topics: Alanine Transaminase; Amino Acid Chloromethyl Ketones; Animals; Apoptosis; Aspartate Aminotransferases; Bile Acids and Salts; Caspase Inhibitors; Chemical and Drug Induced Liver Injury; Diterpenes; Dose-Response Relationship, Drug; Epoxy Compounds; Female; Glucose; Glycogen; Imidazoles; Immunologic Factors; Indoles; Lipopolysaccharides; Liver; Mice, Inbred C57BL; Necrosis; Phenanthrenes; Signal Transduction

The failure to maintain the viability of ischemic myocardium is one of the mechanisms that causes ischemic heart dysfunction after revascularization. Hibernating myocardium is considered to be able to maintain long-term viability during chronic hypoperfusion. Pigment epithelium-derived factor (PEDF) decreases the contractility of hypoxic cardiomyocytes and protects cardiomyocytes against ischemic injury, which is strikingly similar to the pathophysiologic characteristics of hibernating myocardium. It was therefore postulated that PEDF may induce acute ischemic myocardium into a "hibernating-like" state to maintain its viability. Adult Sprague-Dawley rat models of acute myocardial infarction were surgically established. Lentiviral vectors carrying the

Topics: Animals; Biomarkers; Disease Models, Animal; Eye Proteins; Gene Expression; Genes, Reporter; Genetic Therapy; Genetic Vectors; Glycogen; Heart Function Tests; Hibernation; Lentivirus; Male; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Myocardium; Necrosis; Nerve Growth Factors; Positron-Emission Tomography; Rats; Rats, Sprague-Dawley; Serpins

Zinc oxide nanoparticles (ZnO NPs) are widely used in industry and cosmetic products with promising investment in medical diagnosis and treatment. However, these particles may reveal a high potential risk for human health with no information about hepatotoxicity that might be associated with their exposure. The present work was carried out to investigate the histological and histochemical alterations induced in the hepatic tissues by naked 35nm ZnO NPs. Male Wistar albino rats were exposed to ZnO NPs at a daily dose of 2mg/kg for 21days. Liver biopsies from all rats under study were subjected to histopathological examinations. In comparison with the control rats, the following histological and histochemical alterations were demonstrated in the hepatic tissues of rats exposed to ZnO NPs: sinusoidal dilatation, Kupffer cells hyperplasia, lobular and portal triads inflammatory cells infiltration, necrosis, hydropic degeneration, hepatocytes apoptosis, anisokaryosis, karyolysis, nuclear membrane irregularity, glycogen content depletion and hemosidrosis. The findings of the present work might indicate that ZnO NPs have potential oxidative stress in the hepatic tissues that may affect the function of the liver. More work is needed to elucidate the toxicity and pathogenesis of zinc oxide nanoparticles on the vital organs.

Topics: Animals; Apoptosis; Chemical and Drug Induced Liver Injury; Glycogen; Hemosiderosis; Hepatocytes; Kupffer Cells; Liver; Male; Nanoparticles; Necrosis; Particle Size; Rats, Wistar; Surface Properties; Zinc Oxide

McArdle disease is caused by a deficiency of myophosphorylase and currently a satisfactory treatment is not available. The injection of notexin into, or the layering of notexin onto, the muscles of affected sheep resulted in necrosis followed by regeneration of muscle fibres with the expression of both non-muscle isoforms of phosphorylase within the fibres and a reduction of the amount of glycogen in the muscle with an increase in the strength of contraction and a decrease in fatiguability in the muscle fibres. The sustained re-expression of both the brain and liver isoforms of phosphorylase within the muscle fibres provides further emphasis that strategies to enhance the re-expression of these isoforms should be investigated as a possible treatment for McArdle disease.

Topics: Animals; Blotting, Western; Elapid Venoms; Glycogen; Glycogen Phosphorylase; Glycogen Storage Disease Type V; Isoenzymes; Male; Muscle Fatigue; Muscle Strength; Muscle, Skeletal; Necrosis; Neurotoxins; Phosphorylases; Regeneration; Sheep; Time Factors

This study aimed to investigate the protective and regulatory effects of silymarin (SMN) and melatonin (MEL) on streptozotocin (STZ)-induced diabetic changes in cytochrome P450 3A2 (CYP 3A2) and glutathione peroxidase (GPX) expression and antioxidant status in the liver. Male Wistar rats were divided into five groups, including: control (C), untreated diabetic animals (D), SMN-treated diabetics (S, 50 mg/kg, orally), MEL-treated diabetics (M, 10 mg/kg, i.p.), and SMN plus MEL-treated diabetics (S+M). Diabetes was induced by a single intraperitoneal injection of STZ (50 mg/kg). The blood glucose level, daily urinary volume and body weight changes were measured. After the 28 days treatment period, antioxidant status was analyzed by means of the determination of malondialdehyde (MDA) content, nitric oxide (NO) and total thiol molecules (TTM) levels in the liver. The glycogen depletion in the liver was examined by histochemical staining. The CYP 3A2 and GPX expression at mRNA level was determined using RT-PCT technique. SMN and MEL both individually or in combination prevented from diabetes-induced weight loss and lowered daily urinary volume significantly (p<0.05). None of the test compounds could lower the blood glucose level significantly (p>0.05). Both SMN and MEL could convert the diabetes induced elevated levels of MDA and NO and the diabetes-reduced TTM content to the control level. Moreover, the diabetes-up regulated CYP 3A2 and down regulated GPX, returned to normal values after SMN treatment. Histochemical and histopathological examinations revealed that the diabetes-induced glycogen-depletion and single cell necrosis markedly improved with the SMN and SMN plus MEL treatment. Our data suggest that the STZ-induced diabetes in addition of disturbing the antioxidant status, alters the expression levels of CYP 3A2 and GPX. Moreover, the SMN and SMN plus MEL treatment was able to normalize both the antioxidant status and the expression of CYP 3A2 and GPX in the liver of diabetic rats.

Topics: Animals; Antioxidants; Blood Glucose; Cytochrome P-450 CYP3A; Diabetes Mellitus, Experimental; Drug Therapy, Combination; Glutathione Peroxidase; Glycogen; Liver; Male; Malondialdehyde; Melatonin; Necrosis; Nitric Oxide; Phytotherapy; Plant Extracts; Rats; Rats, Wistar; RNA, Messenger; Silybum marianum; Silymarin; Sulfhydryl Compounds; Urination; Weight Loss

We previously demonstrated that hexokinase (HK) II plays a key role in the pathophysiology of ischemia-reperfusion (I/R) injury of the heart (Smeele et al. Circ Res 108: 1165-1169, 2011; Wu et al. Circ Res 108: 60-69, 2011). However, it is unknown whether HKII also plays a key role in I/R injury and healing thereafter in skeletal muscle, and if so, through which mechanisms. We used male wild-type (WT) and heterozygous HKII knockout mice (HKII(+/-)) and performed in vivo unilateral skeletal muscle I/R, executed by 90 min hindlimb occlusion using orthodontic rubber bands followed by 1 h, 1 day, or 14 days reperfusion. The contralateral (CON) limb was used as internal control. No difference was observed in muscle glycogen turnover between genotypes at 1 h reperfusion. At 1 day reperfusion, the model resulted in 36% initial cell necrosis in WT gastrocnemius medialis (GM) muscle that was doubled (76% cell necrosis) in the HKII(+/-) mice. I/R-induced apoptosis (29%) was similar between genotypes. HKII reduction eliminated I/R-induced mitochondrial Bax translocation and oxidative stress at 1 day reperfusion. At 14 days recovery, the tetanic force deficit of the reperfused GM (relative to control GM) was 35% for WT, which was doubled (70%) in HKII(+/-) mice, mirroring the initial damage observed for these muscles. I/R increased muscle fatigue resistance equally in GM of both genotypes. The number of regenerating fibers in WT muscle (17%) was also approximately doubled in HKII(+/-) I/R muscle (44%), thus again mirroring the increased cell death in HKII(+/-) mice at day 1 and suggesting that HKII does not significantly affect muscle regeneration capacity. Reduced HKII was also associated with doubling of I/R-induced fibrosis. In conclusion, reduced muscle HKII protein content results in impaired muscle functionality during recovery from I/R. The impaired recovery seems to be mainly a result of a greater susceptibility of HKII(+/-) mice to the initial I/R-induced necrosis (not apoptosis), and not a HKII-related deficiency in muscle regeneration.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Disease Models, Animal; Down-Regulation; Fibrosis; Glycogen; Hexokinase; Hindlimb; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microcirculation; Mitochondria, Muscle; Muscle Fatigue; Muscle Strength; Muscle, Skeletal; Necrosis; Neovascularization, Physiologic; Oxidative Stress; Recovery of Function; Regeneration; Regional Blood Flow; Reperfusion Injury; Time Factors

We studied ultrastructural reorganization of the gingival mucosa in chronic gingivitis. It was found that chronic inflammation leads to significant intracellular reorganization of epitheliocytes in the basal and prickle cell layers of gingival epithelium and their pronounced structural and functional heterogeneity. The main ultrastructural alterations of epitheliocytes in the basal and prickle cell layers include pronounced vacuolization of the perinuclear zone (partial necrosis), formation of thick tonofilament bundles, focal lysis and sequestration of glycogen, and destruction and reduction of intracellular junctions in some cases accompanied by acantholytic alterations. Chronic inflammation in the gingival mucosa induced extensive remodeling of the lamina propria manifested in multiplication of the basement membrane and obturation of blood vessels with collagen fibrils.

Topics: Adult; Basement Membrane; Biopsy; Blood Vessels; Chronic Disease; Cytoplasm; Epithelial Cells; Gingiva; Gingivitis; Glycogen; Humans; Inflammation; Intercellular Junctions; Microscopy, Electron; Mucous Membrane; Necrosis

Increasing energy storage capacity by elevating creatine and phosphocreatine (PCr) levels to increase ATP availability is an attractive concept for protecting against ischaemia and heart failure. However, testing this hypothesis has not been possible since oral creatine supplementation is ineffectual at elevating myocardial creatine levels. We therefore used mice overexpressing creatine transporter in the heart (CrT-OE) to test for the first time whether elevated creatine is beneficial in clinically relevant disease models of heart failure and ischaemia/reperfusion (I/R) injury.. CrT-OE mice were selected for left ventricular (LV) creatine 20-100% above wild-type values and subjected to acute and chronic coronary artery ligation. Increasing myocardial creatine up to 100% was not detrimental even in ageing CrT-OE. In chronic heart failure, creatine elevation was neither beneficial nor detrimental, with no effect on survival, LV remodelling or dysfunction. However, CrT-OE hearts were protected against I/R injury in vivo in a dose-dependent manner (average 27% less myocardial necrosis) and exhibited greatly improved functional recovery following ex vivo I/R (59% of baseline vs. 29%). Mechanisms contributing to ischaemic protection in CrT-OE hearts include elevated PCr and glycogen levels and improved energy reserve. Furthermore, creatine loading in HL-1 cells did not alter antioxidant defences, but delayed mitochondrial permeability transition pore opening in response to oxidative stress, suggesting an additional mechanism to prevent reperfusion injury.. Elevation of myocardial creatine by 20-100% reduced myocardial stunning and I/R injury via pleiotropic mechanisms, suggesting CrT activation as a novel, potentially translatable target for cardiac protection from ischaemia.

Topics: Animals; Cell Line; Creatine; Disease Models, Animal; Energy Metabolism; Glycogen; Heart Failure; Magnetic Resonance Imaging, Cine; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitochondria, Heart; Mitochondrial Membrane Transport Proteins; Mitochondrial Permeability Transition Pore; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardial Stunning; Myocardium; Necrosis; Oxidative Stress; Phosphocreatine; Time Factors; Up-Regulation; Ventricular Function, Left; Ventricular Remodeling

Several recent reports proposed that astrocyte death might precede neuronal demise after focal ischemia, contrary to the conventional view that astrocytes are more resistant to injury than neurons. Interestingly, there are findings supporting each of these opposing views. To clarify these controversies, we assessed astrocyte viability after 2-h middle cerebral artery occlusion in mice. In contrast to neighboring neurons, astrocytes were alive and contained glycogen across the ischemic area 6 h after reperfusion, and at the expanding outer border of the infarct at later time points. These glycogen-positive astrocytes had intact plasma membranes. Astrocytes lost plasmalemma integrity much later than neurons: 19 +/- 22 (mean +/- standard deviation), 58 +/- 14 and 69 +/- 3% of astrocytes in the perifocal region became permeable to propidium iodide (PI) at 6, 24, 72 h after ischemia, respectively, in contrast to 81 +/- 2, 96 +/- 3, 97 +/- 2% of neurons. Although more astrocytes in the cortical and subcortical core regions were PI-positive, their numbers were considerably less than those of neurons. Lysosomal rupture (monitored by deoxyribonuclease II immunoreactivity) followed a similar time course. Cytochrome-c immunohistochemistry showed that astrocytes maintained mitochondrial integrity longer than neurons. EM confirmed that astrocyte ultrastructure including mitochondria and lysosomes disintegrated much later than that of neurons. We also found that astrocytes died by a delayed necrosis without significantly activating apoptotic mechanisms although they rapidly swelled at the onset of ischemia.

Topics: Animals; Apoptosis; Astrocytes; Cell Count; Cerebral Cortex; Cytochromes c; Glycogen; Immunohistochemistry; Infarction, Middle Cerebral Artery; Mice; Microscopy, Electron; Mitochondria; Necrosis; Neurons; Time Factors

The neuropeptide vasoactive intestinal peptide (VIP) is anti-inflammatory and protective in the immune and nervous systems, respectively. This study demonstrated in corneal endothelial (CE) cells injured by severe oxidative stress (1.4 mM H(2)O(2)) in bovine corneal organ cultures that VIP pre-treatment (0, 10(-10), 10(-8), and 10(-6) M; 15 min), in a VIP concentration-dependent manner, switched the inflammation-causing necrosis to inflammation-neutral apoptosis (showing annexin V-binding, chromatin condensation, and DNA fragmentation) and upheld ATP levels in a VIP antagonist (SN)VIPhyb-sensitive manner, while up-regulated mRNA levels of the anti-apoptotic Bcl-2 and the differentiation marker N-cadherin in a kinase A inhibitor-sensitive manner. As a result, VIP, in a concentration-dependent and VIP antagonist-sensitive manners, promoted long-term CE cell survival. ATP levels, a determining factor in the choice of apoptosis versus necrosis, measured after VIP pre-treatment and 0.5 min post-H(2)O(2) were 39.6 +/- 3.3, 50.8 +/- 6.2, 60.1 +/- 4.8, and 53.6 +/- 5.3 pmoles/microg protein (mean +/- SEM), respectively (p < 0.05, anova). VIP treatment alone concentration-dependently increased levels of N-cadherin (Koh et al. 2008), the phosphorylated cAMP-responsive-element binding protein and Bcl-2, while 10(-8) M VIP, in a VIP antagonist (SN)VIPhyb-sensitive manner, increased ATP level by 38% (p < 0.02) and decreased glycogen level by 32% (p < 0.02). VPAC1 (not VPAC2) receptor was expressed in CE cells. Thus, CE cell VIP/VPAC1 signaling is both anti-inflammatory and protective in the corneal endothelium.

Topics: Adenosine Triphosphate; Animals; Annexin A5; Apoptosis; Cadherins; Cattle; Cell Survival; Dose-Response Relationship, Drug; Endothelial Cells; Epithelium, Corneal; Gene Expression Regulation; Glycogen; Hydrogen Peroxide; In Vitro Techniques; Necrosis; Oxidants; Oxidative Stress; Propidium; Proto-Oncogene Proteins; RNA, Messenger; Vasoactive Intestinal Peptide

The aim of this study was to investigate the effect of misoprostol, silymarin or the co-administration of misoprostol + silymarin on the carbon tetrachloride (CCl(4))-induced hepatic injury in rats. Misoprostol (10, 100, 1000 microg/kg), silymarin (25 mg/kg) or misoprostol (100 microg/kg) + silymarin (25 mg/kg) was given once daily orally simultaneously with CCl(4) and for 15 days thereafter. The results showed that misoprostol (10, 100 or 1000 microg/kg) conferred significant protection against the hepatotoxic actions of CCl(4) in rats, reducing serum alanine aminotransferase (ALT) levels by 24.7%, 42.6% and 49.4%, respectively compared with controls. Misoprostol, given at 100 or 1000 microg/kg, decreased aspartate aminotransferase (AST) by 28 and 43.6% and alkaline phosphatase (ALP) by 19.3% and 53.4% respectively. Meanwhile, silymarin reduced ALT, AST and ALP levels by 62.7%, 66.1% and 65.1% respectively. The co-administration of misoprostol (100 microg/kg) and silymarin (25 mg/kg) resulted in 61.4%, 66.1% and 57.5% reduction in ALT, AST and ALP levels respectively. Histopathological alterations and depletion of hepatocyte glycogen and DNA content by CCl(4) were markedly reduced after treatment with misoprostol, silymarin or misoprostol + silymarin. Image analysis of liver specimens revealed a marked reduction in liver necrosis; area of damage: 32.4%, 24% and 10.2% after misoprostol (10, 100 or 1000 microg/kg), 7.2% after silymarin and 10.9% after treatment with misoprostol 100 microg/kg + silymarin, compared with CCl(4) control group (46.7%). These results indicate that treatment with misoprostol protects against hepatocellular necrosis induced by CCl(4). This study suggests a potential therapeutic use for misoprostol in liver injury.

Topics: Animals; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; DNA; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Glycogen; Liver Diseases; Liver Function Tests; Male; Misoprostol; Necrosis; Protective Agents; Rats; Rats, Sprague-Dawley; Silymarin

Dexamethasone (DEXA) administration has been associated with serum alanine aminotransferase (ALT) elevations that may result from enhanced ALT expression. The aim of our current study was to compare liver vs. serum ALT activity and to examine the onset of any hepatocellular changes. Groups of 4 male Sprague-Dawley rats were administered a single dose of DEXA or corn oil at 12, 16, and 24 h prior to euthanasia or once-daily for 2, 3, or 4 days. All (nonfasted) rats were necropsied together on Day 5. While DEXA incrementally increased liver ALT activity in the 1-, 2-, 3-, and 4-day treatment groups (maximal, 3.7-fold), liver aspartate aminotransferase (AST) never exceeded 1.4-fold over control. Significant hepatic glycogen elevations were detected after DEXA treatment, which correlated with microscopic observations. Serum ALT, AST, sorbitol dehydrogenase, and glutamate dehydrogenase (GLDH) increased after 2, 3, and 4 days of DEXA dosing (1.3-10.3-fold). DEXA-related necropsy findings included pale livers consistent with glycogen deposition. The relative percent liver to body weight was elevated in all DEXA-treated rats. Hepatocellular necrosis was observed in 1/4 rats at 12 h, 2/4 rats at 2 days, 4/4 rats at 3 days, and 3/4 rats at 4 days. DEXA treatment <2 days failed to produce consistent evidence of hepatic injury, as detected by serum biomarkers and pathology assessment. However, early DEXA treatment did correlate with apparent ALT induction. Ultimately, this may explain some early asymptomatic serum ALT elevations seen clinically.

Topics: Alanine Transaminase; Animals; Biomarkers; Dexamethasone; Glucocorticoids; Glycogen; Liver; Male; Necrosis; Rats; Rats, Sprague-Dawley; Time Factors; Up-Regulation

Body temperature may critically affect mechanisms of liver injury in acetaminophen (APAP) hepatotoxicity. In addition, mild hypothermia is used to treat intracranial hypertension in human liver failure without detailed information on its effects on the injured liver itself. Therefore, we investigated the effects of body temperature on the progression of APAP-induced liver injury in mice.. Male C57BL6 mice treated with saline or APAP (300 mg/kg intraperitoneally) were maintained at normothermia (35.5-37.5 degrees C) by external warming or were allowed to develop mild hypothermia (32.0-35.0 degrees C) after 2 hours from APAP administration.. Mild hypothermia resulted in improved survival after APAP intoxication. Liver damage was reduced, as assessed histologically and by plasma alanine aminotransferase levels. Early effects of hypothermia included a reduction of hepatic congestion and improved recovery of glycogen stores. At later time points (8-12 hours), APAP-treated mice that were maintained at normothermia manifested increased hepatocyte apoptosis, as assessed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining and cleavage of poly(adenosine diphosphate-ribose) polymerase. Mild hypothermia did not affect the formation of APAP-protein adducts or the depletion of glutathione, nor did it abrogate hepatocyte DNA synthesis.. Mild hypothermia improved survival and attenuated liver injury and apoptosis in APAP-treated mice by reducing hepatic congestion and improving glycogen recovery without affecting hepatic regeneration. Results of the study underscore the need for a strict control of body temperature in animal models of liver failure and suggest that the benefits of mild hypothermia in liver failure may extend beyond those related to reduced cerebral complications.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Apoptosis; Body Temperature; Cell Count; Cell Division; Chemical and Drug Induced Liver Injury; DNA Adducts; Glutathione; Glycogen; Hemoglobins; Hepatocytes; Hypothermia, Induced; In Situ Nick-End Labeling; Liver; Male; Mice; Mice, Inbred C57BL; Necrosis; Severity of Illness Index; Survival Rate

Aqueous extract of the fruits of Solanum xanthocarpum Schrad. & Wendl. (Solanaceae) was investigated for hypoglycaemic activity in rats and mice. Screening for the hypoglycaemic activity was assessed on normoglycaemic, alloxan treated hyperglycaemic and glucose loaded rats along with in vitro study on glucose utilization by isolated rat hemidiaphragm. The various haematological and biochemical parameters were also studied. The extract was found to possess significant hypoglycaemic activity when compared with the reference standard glibenclamide. The in vitro study on glucose utilization by isolated rat hemidiaphragm suggests that the aqueous extract may have direct insulin like activity which enhances the peripheral utilization of glucose and have extra pancreatic effect. The toxicity studies report safety usage of the plant extract.

Topics: Alloxan; Animals; Blood Glucose; Cholesterol, VLDL; Diabetes Mellitus, Experimental; Diaphragm; Fatty Liver; Fruit; Glyburide; Glycogen; Hypoglycemic Agents; India; Kidney; Lipoproteins, HDL; Liver; Medicine, Traditional; Mice; Necrosis; Plant Extracts; Rats; Rats, Wistar; Solanaceae; Triglycerides; Water; Weight Loss

We studied tissue and intracellular reorganization of the liver during total body hypothermia and evaluated regeneration strategies at different levels of structural organization. Hypothermia results in morphofunctional changes in the liver (degeneration, lysis, necrobiosis, and focal necrosis of hepatocytes developing against the background of disorders in blood and lymph circulation). Decreased sinusoid/hepatocyte volume ratio is the key factor in tissue reorganization of the liver. Intracellular reorganization of hepatocytes is characterized by dysproportional changes in the volume and surface densities of the main cytoplasmic organelles involved in biosynthesis and energy production.

Topics: Animals; Cell Nucleus; Endoplasmic Reticulum, Rough; Endoplasmic Reticulum, Smooth; Glycogen; Hepatocytes; Hypothermia, Induced; Liver; Lysosomes; Male; Mitochondria, Liver; Necrosis; Organ Size; Rats; Rats, Wistar; Time Factors

Topics: Animals; Cell Transformation, Neoplastic; DNA; Female; Fibroblasts; Glycogen; Lipids; Necrosis; Neoplasms, Experimental; Proteins; Rats; RNA; Spectrum Analysis, Raman; Uterine Cervical Neoplasms

Dichloroacetic acid (DCA) is carcinogenic to the B6C3F(1) mouse and the F344 rat. Given the carcinogenic potential of DCA in rodent liver and the known concentrations of this compound in drinking water, reliable biologically based models to reduce the uncertainty of risk assessment for human exposure to DCA are needed. Development of such models requires identification and quantification of premalignant hepatic lesions, identification of the doses at which these lesions occur, and determination of the likelihood that these lesions will progress to cancer. In this study we determined the dose response of histopathologic changes occurring in the livers of mice exposed to DCA (0.05-3.5 g/L) for 26-100 weeks. Lesions were classified as foci of cellular alteration smaller than one liver lobule (altered hepatic foci; AHF), foci of cellular alteration larger than one liver lobule (large foci of cellular alteration; LFCA), adenomas (ADs), or carcinomas (CAs). Histopathologic analysis of 598 premalignant lesions revealed that (a)) each lesion class had a predominant phenotype; (b)) AHF, LFCA, and AD demonstrated neoplastic progression with time; and (c)) independent of DCA dose and length of exposure effects, some toxic/adaptive changes in non-involved liver were related to this neoplastic progression. A lesion sequence for carcinogenesis in male B6C3F(1) mouse liver has been proposed that will enable development of a biologically based mathematical model for DCA. Because all classes of premalignant lesions and CAs were found at both lower and higher doses, these data are consistent with the conclusion that nongenotoxic mechanisms, such as negative selection, are relevant to DCA carcinogenesis at lower doses where DCA genotoxicity has not been observed.

Topics: Adenoma, Acidophil; Adenoma, Basophil; Adenoma, Liver Cell; Animals; Carcinogenicity Tests; Dichloroacetic Acid; Dose-Response Relationship, Drug; Glycogen; Linear Models; Liver Neoplasms, Experimental; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Necrosis; Rats; Rats, Inbred F344; Water Pollutants

Kupffer cells are the tissue macrophages in the liver and play an important role in the defense mechanisms of the body. However, their role in liver function and hepatocellular activity remains unclear. This study was therefore undertaken to investigate the effect of gadolinium chloride-induced Kupffer cell dysfunction on liver function and hepatocellular signaling activity in mice and to establish an animal model for studying the role of Kupffer cells in vivo. Kunming mice were intraperitoneally injected with different doses of gadolinium chloride (GdCl3), a selective inhibitor of Kupffer cells, and the mice were sacrificed at different time periods following the drug administration. Hepatotoxicity and Kupffer cell function, as well as the levels of signaling molecules and inflammatory mediators in liver tissue, were measured. We demonstrated that the administration of 10-20 mg/kg GdCl3 caused apoptosis of Kupffer cells and blocked the Kupffer cell effector function, as shown by a decrease in CD68 expression and phagocytic activity. In addition, the NO, PGE2 and cAMP levels in the liver were also reduced significantly. Furthermore, 20 mg/kg GdCl3 decreased the levels of cNOS, PKC and NF-kappaB p65 expression by 26.6, 68 and 64%, respectively. In contrast, hepatotoxicity was not observed when the same doses of GdCl3 were used. Moreover, we found that Kupffer cell function and the NO, PGE2 and cAMP contents, as well as PKC and NF-kappaB p65 levels in the liver were only partially, but not fully recovered in up to six days following 20 mg/kg GdCl3 injection. However, the administration of higher doses of GdCl3 (40 mg/kg) caused both hepatotoxicity and Kupffer cell necrosis, as well as an increased release of TNF, NO, and PGE2 in the liver. These results indicate that administration of suitable doses of GdCl3 blocked the effector function of Kupffer cells selectively, but did not cause liver parenchymal cell toxicity, and provide a frame-work for the establishment of an animal model for studying the role of Kupffer cells in signaling in the liver. Lastly, the present study also provides evidence that shows there is a positive association between the expression of cAMP, PKC, or NF-kappaB and the levels of NO, PGE2 and TNF in the liver of Kupffer-cell-blocked mice, and suggests that Kupffer cells may play a part in mediating liver function and hepatocellular activity.

Topics: Adenosine Triphosphatases; Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Apoptosis; Cell Line; Cyclic AMP; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Gadolinium; Glycogen; Image Processing, Computer-Assisted; Immunohistochemistry; In Situ Hybridization; Kupffer Cells; Liver; Mice; Microscopy, Electron; Necrosis; NF-kappa B; Phagocytosis; Signal Transduction; Time Factors

Topics: Analysis of Variance; Animals; Body Weight; Diabetes Mellitus, Experimental; Disease Models, Animal; Glycogen; Heart; Hemodynamics; Humans; Isoproterenol; L-Lactate Dehydrogenase; Lactates; Male; Myocardial Infarction; Myocardial Ischemia; Myocardium; Necrosis; Organ Size; Rats; Rats, Wistar

The growth-stimulatory actions of tumor necrosis factor alpha (TNF-alpha) after partial hepatectomy (PH) are difficult to reconcile with its well-established role in the genesis of liver injury. The lethal actions of TNF are thought to involve the induction of oxidant production by mitochondria. It is not known if TNF initiates mitochondrial oxidant production after PH. Furthermore, if this potentially toxic response follows PH, it is not clear how hepatocytes defend themselves sufficiently so that replication, rather than death, occurs. These studies test the hypothesis that TNF does increase mitochondrial oxidant production after PH but that these oxidants primarily promote the induction of antioxidant defenses in regenerating hepatocytes. Consistent with this concept, H2O2 production by liver mitochondria increases from 5 minutes to 3 hours after PH, beginning before the transient inductions of hepatic NF kB activity (which peaks at 30 minutes post-PH) and uncoupling protein-2 (UCP-2) (which begins around 30 minutes and peaks from 6-24 hours post-PH). Pretreatment with neutralizing anti-TNF antibodies, which inhibits hepatocyte DNA synthesis after PH, also reduces post-PH hepatic mitochondrial oxidant production by 80% and inhibits NF kappaB activation and UCP-2 induction by 50% and 80%, respectively. In contrast, pretreatment with D609, an agent that inhibits phosphatidylcholine-specific phospholipase C, neither inhibits regenerative induction of mitochondrial oxidant production, UCP-2 expression, nor hepatocyte DNA synthesis, although it inhibits NF kappaB activation by 50%. Given published evidence that NF kappaB is antiapoptotic and that UCP-2 may decrease mitochondrial oxidant production in some cells, these results suggest that TNF-dependent increases in oxidant production by liver mitochondria promote the induction of antioxidant defenses in the regenerating liver.

Topics: Animals; Antibodies; Bridged-Ring Compounds; DNA; Glycogen; Hydrogen Peroxide; Ion Channels; Liver; Liver Regeneration; Male; Membrane Transport Proteins; Mice; Mice, Inbred C57BL; Mitochondria, Liver; Mitochondrial Proteins; Necrosis; Norbornanes; Oxidants; Phosphodiesterase Inhibitors; Proteins; Thiocarbamates; Thiones; Tumor Necrosis Factor-alpha; Uncoupling Protein 2

To study the histochemical alterations of hookworm L3 administered in a challenge dose to mice vaccinated previously with the larvae. Male Kunming strain mice vaccinated subcutaneously with 500 living Ancylostoma caninum L3 once every 2 weeks for a total of three immunizations before a final challenge with 500 L3 one week after the final immunization. The abdominal skin with underlying subcutaneous tissue and muscle were removed from the site of percutaneous challenge entry (from 2-3 mice), and fixed in absolute alcohol, cold acetone and 10% neutralized formalin. The tissue sections containing the L3 from the challenge dose were then stained histochemically of glycogen, RNA, DNA alkaline protein, acid mucopolysaccharide, collagen, reticulin, alkaline phosphatase (AKP) and adenosine triphosphatase (ATPase). Skin samples from non-immunized mice that were also subcutaneously inoculated with the L3 served as negative control. The L3 identified in cutaneous sections from vaccinated mice at 6-72 hours post-challenge exhibited reductions in parasite glycogen, alkaline protein, RNA and DNA, as well as reductions in acid mucopolysaccharide, collagen and reticulin contents in the parasite cuticle. There were also reduced enzyme AKP and ATPase activities. In contrast L3, identified in sections from non-immunized mice exhibited a normal histochemical appearance, as did some L3 who survived in vaccinated mice at 7-14 days post-challenge. Vaccination results in hookworm L3 damage which is manifested by reduced histochemical staining for the challenge inoculum of parasites. There is also reduced hydrolytic enzyme activity. The observed changes could reflect either host-mediated parasite structural damage and disintegration or possibly anti-metabolic properties of the host immune response.

Topics: Ancylostoma; Ancylostomiasis; Animals; DNA, Helminth; Glycogen; Helminth Proteins; Larva; Male; Mice; Necrosis; RNA, Helminth; Vaccines

Few results, and those controversial, have been published on ischemic preconditioning followed by low-flow ischemia. The aim of this study was to assess whether ischemic preconditioning: (1) confers protection against severe underperfusion; and (2) is mediated by mobilization of proglycogen, resulting in increased anaerobic glycolysis and reduced myocardial injury. Isolated rat hearts were retrogradely perfused and subjected to either 25 min low-flow ischemia (0.6 ml/min) followed by 30 min reperfusion (IC; n=5), or the same protocol preceded by two cycles of 5 min no-flow ischemia and 5 min reperfusion (PC; n=7). Additionally, hearts (n=52) were freeze-clamped at different time points throughout the protocol. Preconditioning improved functional recovery (developed force X heart rate in PC hearts: 54 v 21% in IC hearts; P<0.01) and reduced ischemic damage (cumulative release of creatine kinase during reperfusion: 93 v 215 micro/g dry weight; P<0.05). During ischemia and reperfusion, release of adenosine and the sum of purines was smaller in PC hearts (P<0.05), while lactate release was similar in the two groups. PC reduced both macroglycogen and proglycogen by c. 60% (P<0.01) resulting in constant glycogen levels during low-flow ischemia. In contrast, in IC hearts, both fractions decreased by c. 60% during underperfusion (P<0.01). These results demonstrate that: (1) ischemic preconditioning reduces injury due to severe flow reduction; and (2) preconditioning reduced glycogenolysis without affecting anaerobic glycolysis, suggesting increased glucose uptake.

Topics: Adenosine Triphosphate; Animals; Carbohydrate Metabolism; Glucose; Glycogen; In Vitro Techniques; Ischemic Preconditioning, Myocardial; Lactic Acid; Male; Myocardial Contraction; Myocardial Reperfusion Injury; Myocardium; Necrosis; Perfusion; Phosphocreatine; Purines; Rats; Rats, Wistar

A severe myopathy leading to death or euthanasia was identified in 4 Belgian and 4 Percheron draught horses age 2-21 years. Clinical signs ranged from overt weakness and muscle atrophy in 2 horses age 2 and 3 years, to recumbency with inability to rise in 6 horses age 4-21 years. In 5 horses there was mild to severe increases in muscle enzyme levels. Clinical diagnoses included equine motor neuron disease (2 horses), post anaesthetic myopathy (2 horses), exertional myopathy (2 horses), myopathy due to unknown (one horse), and equine protozoal myelitis (one horse). Characteristic histopathology of muscle from affected horses was the presence of excessive complex polysaccharide and/or glycogen, revealed by periodic acid-Schiff staining in all cases and by electron microscopy in one case. Evaluation of frozen section histochemistry performed on 2 cases indicated that affected fibres were Type 2 glycolytic fibres. Subsarcolemmal and intracytoplasmic vacuoles were most prominent in 3 horses age 2-4 years, and excessive glycogen, with little or no complex polysaccharide, was the primary compound stored in affected muscle in these young horses. Myopathic changes, including fibre size variation, fibre hypertrophy, internal nuclei, and interstitial fat infiltration, were most prominent in 5 horses age 6-21 years, and the accumulation of complex polysaccharide appeared to increase with age. Mild to moderate segmental myofibre necrosis was present in all cases.

Topics: Animals; Atrophy; Female; Glycogen; Glycogen Storage Disease; Histocytochemistry; Horse Diseases; Horses; Hypertrophy; Male; Microscopy, Electron, Scanning Transmission; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Diseases; Necrosis; Polysaccharides

1. The effects of fasting for 48 h were investigated in C57BL/10 (wild type) and age-matched C57BL/10 dystrophin-deficient (mdx) mice. 2. Fasting resulted in an increased percentage of necrotic fibres in muscles from the hindlimb and lumbar regions of mdx mice. The percentage of necrotic fibres of forelimb and chest muscles of mdx mice was unaltered by fasting. In wild-type mice, very few necrotic fibres were observed after fasting. 3. The necrotic changes in fasted mdx muscle were not accompanied by altered energy status as evaluated by muscle ATP and phosphocreatine concentrations. 4. A significantly decreased rectal temperature was observed in mdx but not in wild-type mice after fasting. 5. Fasting would normally be expected to cause a reduction in muscle fibre size. The high prevalence of necrosis in fasted mdx mice is therefore an unusual response that may be related to disturbance of the mechanisms which, in the fed state, compensate for the dystrophin deficiency in these animals.

Topics: Animals; Body Temperature; Body Weight; Dystrophin; Fasting; Glycogen; Mice; Mice, Inbred mdx; Muscle Proteins; Muscle, Skeletal; Necrosis

Short-term myocardial hibernation of 3 hours resulting from a moderate resting coronary flow reduction has been reproduced in pigs. This study was designed to determine whether any structural changes accompany short-term hibernation caused by a moderate flow reduction maintained for 24 hours and whether any such structural alterations are reversible after reperfusion.. A severe left anterior descending coronary artery (LAD) stenosis was created with a reduction of resting flow to approximately 60% of baseline and maintained for 24 hours. Regional coronary flow was measured by a flowmeter; wall thickening was determined by echocardiography, and local metabolic changes were measured. Of 17 pigs, 11 completed the study protocol of 24 hours. The LAD flow was reduced from 0.91 +/- 0.11 to 0.52 +/- 0.13 mL.min-1.g-1, a 43% mean decrease, at 15 minutes after the LAD stenosis and was maintained at 0.56 +/- 0.11 mL.min-1.g-1 at 24 hours. The reduction of regional coronary flow initially produced acute myocardial ischemia, as evidenced by reduced regional wall thickening (from 37.2 +/- 6.9% at baseline to 11.5 +/- 6.8%), regional lactate production (-0.34 +/- 0.28 mumol.g-1.min-1), and a decrease in regional coronary venous pH (from 7.41 +/- 0.035 at baseline to 7.30 +/- 0.030). At 24 hours, the reductions in coronary flow and wall thickening were maintained relatively constant and the rate-pressure product was relatively unchanged, but lactate production ceased and regional H+ concentration normalized, with a tendency toward a further reduction in regional oxygen consumption, from 3.10 +/- 0.90 mL.min-1.100 g-1 at 15 minutes after stenosis to 2.52 +/- 0.95 mL.min-1.100 g-1 at 24 hours (P = .06), indicating metabolic adaptation of the hypoperfused regions. Of 11 pigs, 6 were free of myocardial infarction; 3 had patchy necrosis involving 4%, 5%, and 6% of the area at risk; and 2 other pigs had a few scattered myocytes with necrosis, detected only by light and electron microscopy. Ultrastructural changes consisted of a partial loss of myofibrils and an increase in mitochondria and glycogen deposition. Regional wall thickening recovered 1 week after reperfusion in most pigs, and the ultrastructural changes reverted to normal.. In this pig model, moderately ischemic myocardium undergoes metabolic and structural adaptations but preserves the capacity to recover both functionally and ultrastructurally after reperfusion.

Topics: Actin Cytoskeleton; Animals; Coronary Circulation; Coronary Disease; Glycogen; Mitochondria, Heart; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Necrosis; Oxygen Consumption; Swine

An original model of auxiliary heterotopic liver graft perfused by splenopancreatic venous blood flow is studied in pig. Separate portal inflow is performed for each liver and permits efficient function in both graft and native liver. Ten pigs were evaluated 90 days after transplantation, five without portal graft reperfusion (group 1) and five with portal graft reperfusion by splenopancreatic venous blood flow (group 2). Mean biliary output was 4.8 +/- 3.3 ml/hr in group 1, 9.6 +/- 2.3 ml/hr in group 2; biliary conjugated bilirubin level was 0 in group 1, 145 +/- 117 mumol/liter in group 2; intrahepatic glycogen level was 0.9 +/- 1.1 g% in group 1, 4.25 +/- 1.56 g% in group 2. Livers and grafts were weighed to evaluate hepatic mass on the 90th day. A histological examination was performed for each graft and native liver. It was shown that an auxiliary liver graft perfused by splenopancreatic venous blood flow presents satisfying metabolic function for 3 months, without atrophying and without functional impairment of native liver. This original model could be indicated in acute hepatic failure if regeneration of native liver is expected or in metabolic disease when total hepatectomy of the native liver may be unnecessary.

Topics: Animals; Fibrosis; Glycogen; Liver; Liver Circulation; Liver Transplantation; Necrosis; Organ Size; Pancreas; Regional Blood Flow; Spleen; Swine; Transplantation, Heterologous; Veins

Topics: Glycogen; Graft Rejection; Graft Survival; Humans; Liver; Liver Transplantation; Necrosis; Predictive Value of Tests; Transaminases; Transplantation, Homologous

An Arab female child presented with rapidly progressive liver disease, with apparent onset in late infancy and death at 15 months. Microscopy showed panacinar hepatitis, portal and pericellular fibrosis, and diffuse Mallory bodies in the absence of steatosis or significant cholestasis. Hepatic copper concentration was moderately elevated. Known causes of early childhood cirrhosis were excluded. This case meets most of the established criteria of Indian childhood cirrhosis, yet is unusual in its occurrence in a child of Arab ancestry and in having a moderate degree of hepatocellular copper overload.

Topics: Copper; Fatal Outcome; Female; Glycogen; Humans; India; Infant; Kuwait; Liver; Liver Cirrhosis; Lymphocytes; Microscopy, Electron; Necrosis; Neutrophils

We studied eight clear cell tumors of the lung (CCTL) to better define their clinical, immunohistochemical, and ultrastructural features, and to clarify their distinction from other neoplasms, particularly metastatic renal cell carcinoma. Patients ranged in age from 31 to 67 years (mean, 51 years). Seven patients had clinically benign, asymptomatic lesions measuring less than 2 cm in diameter that were devoid of necrosis. The eighth patient had a symptomatic, partially necrotic CCTL 4.5 cm in diameter that metastasized to the liver and peritoneum; the patient died of tumor 17 years after diagnosis. Ultrastructural study of seven CCTL showed interdigitating cell processes (all cases), primitive cell junctions (five of seven cases), intracytoplasmic glycogen (all cases), and rare dense core granules (two of seven cases). Immunohistochemically, paraffin-embedded sections from all eight CCTL were negative for cytokeratin (CK), epithelial membrane antigen (EMA), chromogranin, and vimentin. Focal staining was seen for S-100 protein (three of eight cases), neuron-specific enolase (three cases), synaptophysin (one case), and Leu 7 (one case). Although these findings suggest that at least some CCTL exhibit neuroendocrine differentiation, the tumor's histogenesis remains uncertain. Of more practical importance, the combined absence of CK, EMA, and vimentin in formalin-fixed, paraffin-embedded CCTL virtually precludes confusion with renal cell carcinoma. Although traditionally considered benign, CCTL larger than 2 cm that are symptomatic, and focally necrotic should be regarded as potentially malignant neoplasms.

Topics: Adenocarcinoma; Adult; Aged; Antigens, Differentiation; CD57 Antigens; Cell Nucleus; Cytoplasm; Cytoplasmic Granules; Female; Glycogen; Histocytochemistry; Humans; Immunoenzyme Techniques; Lung Neoplasms; Male; Membrane Proteins; Microscopy, Electron; Middle Aged; Necrosis; Organelles; Phosphopyruvate Hydratase; S100 Proteins; Synaptophysin

Light and electron microscopic observations were made on eosinophilic globule (EG) cells found in 27 subcutaneous malignant fibrous histiocytoma (MFH)-like sarcomas in aged ICR mice. These tumors, which were composed of fibroblast-like cells as the major component, with small numbers of histiocyte-like cells and undifferentiated cells, showed one or more of five growth patterns: storiform, pleomorphic, fascicular, myxoid, and hemangiopericytoma-like. EG cells were interspersed among the tumor cells and were also present in metastatic lesions. They were pleomorphic in shape and contained various numbers of cytoplasmic globules, which were positive with the periodic acid-Schiff reaction and resistant to diastase digestion. Electron microscopic observation revealed that these cells had small finger-like and pseudopodia-like projections, and contained varied numbers of characteristic osmiophilic globules and glycogen particles in the cytoplasm which seemed to become more abundant as the cells differentiated. The osmiophilic globules consisted of a dense homogeneous core and a marginal area rich in small vesicular membranous structures. A small population of EG cells exhibited features suggesting differentiation to fibroblasts; these were characterized by an increased amount of rough endoplasmic reticulum. It is suggested that the EG cell is a neoplastic cell, perhaps derived from a primitive mesenchymal cell, although an inflammatory cell origin is also possible.

Topics: Animals; Cell Differentiation; Cytoplasm; Endoplasmic Reticulum; Female; Fibroblasts; Glycogen; Histiocytes; Histiocytoma, Benign Fibrous; Histocytochemistry; Male; Mice; Mice, Inbred ICR; Microscopy, Electron; Necrosis; Periodic Acid-Schiff Reaction; Sarcoma, Experimental

Topics: Glycogen; Humans; Microscopy, Electron; Muscles; Necrosis; Neuroleptic Malignant Syndrome

Morphologic, histochemical and fluorescent microscopic studies of leiomyomas with necrosis and degenerative changes have been done in 100 patients. Morphologic and functional features of the endometrium and myometrium were examined at tumor-adjacent and remote sites. The study showed no relation between the ischemic changes of uterine leiomyomas and morphological/functional status of the myometrium and endometrium. In the presence of leiomyoma, the endometrium undergoes primarily histophysiological and aging-related changes. The study findings suggest that surgery for necrotic leiomyoma should be organ-sparing.

Topics: Adult; Atrophy; Endometrium; Female; Glycogen; Glycosaminoglycans; Humans; Leiomyoma; Middle Aged; Myometrium; Necrosis; Uterine Neoplasms

Topics: Acid Phosphatase; Adenosine Triphosphatases; Animals; Furosemide; Glycogen; Liver; Male; Necrosis; Rats; Rats, Wistar

The substantia nigra pars reticulata (SNPR) has previously been shown to undergo tissue necrosis following status epilepticus induced by flurothyl in the rat. Even if the rat is ventilated, the SNPR develops necrosis if the epileptic period lasts more than 30 min. Rat brains were frozen in situ after 20 and 60 min of seizure activity and after 60 min of seizure activity followed by 60 min recovery. Labile energy metabolites were then analyzed in the SNPR and in the periaqueductal grey matter (PAG, control region). In the PAG, the metabolite changes during status epilepticus were similar to those reported for cerebral cortex and hippocampus. Measurements showed an unchanged ATP content and energy charge (97% and 98% of control, respectively) and an accumulation of lactate to 9.2 +/- 0.6 mumol/g in the 60-min group. In the PAG, all metabolites measured had returned to control values after 60 min of recovery. In the SNPR, the perturbation of the energy metabolites was much more pronounced during status epilepticus. The concentration of ATP decreased to 75 +/- 3%, the energy charge to 91% +/- 12% and the adenylate pool to 86.7 +/- 5.7% of control. Lactate accumulated to concentrations of 16.1 +/- 1.8 mumol/g and 24.9 +/- 2.3 mumol/g in the 20-min and 60-min groups, respectively. The concentration of lactate was still increased above control after 60 min recovery, whereas the concentration of ATP and the energy charge were lower than control. The findings demonstrate that sustained and intense neuronal activation can cause metabolic disturbance and thereby lead to necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Animals; Glucose; Glycogen; Lactates; Lactic Acid; Necrosis; Periaqueductal Gray; Phosphocreatine; Rats; Status Epilepticus; Substantia Nigra

This study addresses the question of whether the cyclooxygenase inhibitors indomethacin and diclofenac and the glucocorticosteroid dexamethasone ameliorate neuronal necrosis following cerebral ischemia. In addition, since these drugs inhibit the production of prostaglandins and depress phospholipase A2 activity, respectively, the importance of free fatty acids (FFAs) on the development of ischemic neuronal damage was assessed. Neuronal damage was determined in the rat brain at 1 week following 10 min of forebrain ischemia. The cyclooxygenase inhibitors, whether given before or after ischemia, failed to alter the brain damage incurred. Animals given dexamethasone were divided into three groups and the drug was administered at a constant dosage of 2 mg/kg: (a) 2 days, 1 day, and 3 h intraperitoneally before (chronic pretreatment), (b) 3 h intraperitoneally before (acute pretreatment), and (c) 5 min intravenously and 6 h and 1 day intraperitoneally after (chronic posttreatment) induction of ischemia. Acute pretreatment did not affect the histopathological outcome. Chronic posttreatment of animals with dexamethasone ameliorated the damage inflicted on the caudate nucleus, but had no effect on other brain areas investigated. Unexpectedly, the chronic pretreatment aggravated the brain damage and caused seizures following ischemia. Histopathological data showed massive neuronal damage in these brains. The accumulation of FFA levels during ischemia was markedly suppressed, and the decrease in the energy charge was curtailed by chronic pretreatment with dexamethasone. However, brain glucose levels in control animals and lactic acid concentrations following 10 min of ischemia were significantly higher both in the cerebral cortex and in the hippocampus of dexamethasone-treated animals. These results suggest that aggravation of neuronal necrosis by chronic dexamethasone pretreatment could be ascribed to lactic acidosis due to hyperglycemia in combination with an action of dexamethasone on glucocorticoid receptors in the brain.

Topics: Animals; Blood Glucose; Brain Chemistry; Brain Ischemia; Cyclooxygenase Inhibitors; Dexamethasone; Diclofenac; Electroencephalography; Energy Metabolism; Fatty Acids, Nonesterified; Glycogen; Indomethacin; Male; Necrosis; Neurons; Rats; Rats, Inbred Strains

Acute or chronic intoxication of rats with ethanol (intragastric administration at a dose of 8 g/kg or free-choice drinking of 10% ethanol for 3 months) produced no significant changes in contractile function, glycogen content, glucose uptake and lactate release in isolated hearts. Withdrawal syndrome simulated in rats following a short period of severe intoxication with ethanol at a dose of 4-5 g/kg twice daily has demonstrated a 15 and 28% decrease in peak systolic pressure and tension time index, respectively. In this case glucose uptake and lactate release were 2 times higher. Changes in glycogen level were observed three days after the last ethanol administration. The rats, survived after the abstinence period, revealed areas of perivascular myocardial necrosis. It is concluded that withdrawal syndrome plays an important role in pathogenesis of alcoholic cardiomyopathy.

Topics: Alcoholic Intoxication; Alcoholism; Animals; Ethanol; Glucose; Glycogen; Lactates; Lactic Acid; Myocardial Contraction; Myocardium; Necrosis; Rats; Substance Withdrawal Syndrome

An aqueous extract of a poisonous mushroom, Amanita abrupta was injected intraperitoneally into male ICR mice and the acute effects on the liver were studied. Contents of serum glucose and liver glycogen decreased to 60% and 10% of the control levels, respectively, 6 h after injection. Activities of serum glutamic oxaloacetic transaminase and serum glutamic pyruvic transaminase increased to 3- and 8-fold, respectively, 12 h after injection, and the elevated activities were maintained up to 24 h. Activities of the hepatic drug metabolizing enzymes were also reduced 15 h after injection. Histological examination demonstrated massive liver cell necrosis and disappearance of glycogen granules in the liver of the treated animals. Two amino acids, L-2-amino-4-pentynoic acid and L-2-amino-4,5-hexadienoic acid were identified in the mushroom extract. The former caused similar biochemical effects to those of the mushroom extract.

Topics: 5-Aminolevulinate Synthetase; Agaricales; Alanine Transaminase; Alkynes; Amanita; Animals; Aspartate Aminotransferases; Blood Glucose; Glycine; Glycogen; Liver; Male; Mice; Necrosis; Plant Extracts; Sorbic Acid

Topics: Adult; Alcoholism; Female; Glycogen; Humans; Lipids; Male; Middle Aged; Mitochondria; Muscles; Necrosis; Sarcoplasmic Reticulum

Using the indirect immunofluorescence technique, we studied the distribution of myoglobin in normal and ischemic human myocardium obtained at autopsy and at surgery. Glycogen, diastase-PAS staining of the sarcoplasm, and IgG were also studied and compared with the structure of the lesions and the distribution of myoglobin. The surgical material we used was largely free of autolysis and was the most satisfactory. Prolonged fixation of tissues in formaldehyde solution or perfusion fixation of autopsy specimens both proved to be unsatisfactory as myoglobin was absent from the myocardium. This loss presumably represents diffusion of myoglobin due to autolysis and the method of fixation. Another group of autopsy specimens that was briefly fixed by immersion in formaldehyde solution prior to processing was more satisfactory. Although they showed some extracellular diffusion of myoglobin, the autolyzed normal areas could still be clearly differentiated from the autolyzed ischemic areas.

Topics: Amylases; Animals; Coronary Disease; Dogs; Eosinophilia; Fluorescent Antibody Technique; Glycogen; Heart; Humans; Immunoglobulin G; Myocardium; Myoglobin; Necrosis; Periodic Acid-Schiff Reaction

Topics: Animals; Female; Glycogen; Heart; Isoproterenol; Male; Myocardium; Necrosis; Propranolol; Rats; Rats, Inbred Strains

Topics: Adenosine Triphosphate; Adult; Coronary Artery Bypass; Coronary Disease; Creatine Kinase; Glycogen; Hemodynamics; Humans; Hypothermia, Induced; Isoenzymes; Mitochondria, Heart; Myocardium; Necrosis; Phosphocreatine

Myocardium of the children dying suddenly of respiratory infection complicated by pneumonia was studied histologically and histochemically. The observed morphological changes consisted in hemodynamic disorders and degenerative lesions of various intensities associated mostly with the disturbed protein metabolism in the cytoplasm of myocardial cells, especially in microfibrillae.

Topics: Cell Nucleus; Child, Preschool; Death, Sudden; Glycogen; Histocytochemistry; Humans; Infant; Infant, Newborn; Myocardium; Myofibrils; Necrosis; Pneumonia; Respiratory Tract Infections

A malignant fibrous histiocytoma (MFH) arising in the lungs of a 51-year-old man was studied by light and electron microscopy. Features observed were identical to those of MFHs which occur in the skin and subcutaneous tissue and less commonly in other deep locations. By light microscopy, a storiform pattern with admixture of fibroblasts and histiocytes, as well as xanthomatous and giant cells, was noted. Undifferentiated tumor cells along with fibroblasts and histiocytes in different degrees of differentiation were identified ultrastructurally. These findings lend support to the concept that MFH is a sarcoma of primitive mesenchymal cell origin. The addition of the lung as another primary site for the development of this tumor is consistent with the view that MFHs may potentially arise in any part of the body.

Topics: Cytoplasm; Endoplasmic Reticulum; Fibroblasts; Glycogen; Histiocytes; Histiocytoma, Benign Fibrous; Humans; Lung Neoplasms; Lysosomes; Male; Microscopy, Electron; Middle Aged; Necrosis

Two adult brothers became ill within 48 hours of each other, and both had severe myoglobinuria. One brother died of oliguric renal failure. The other did not have renal failure and survived. Acute influenza A infection was documented serologically and from throat washings in the surviving brother, and by isolation of the influenza A virus from throat cultures and lung tissue of the brother who died. It is not certain whether a genetic myopathy made these brothers susceptible to viral-induced myoglobinuria, but a normal response of venous lactate to ischemic work excluded lack of phosphorylase or phosphofructokinase as a cause of the myoglobinuria in the surviving brother. Neither brother had a history of recurrent episodes of myoglobinuria precipitated by exercise, cold, or fasting, thus making carnitine palmityl transferase deficiency unlikely.

Topics: Acute Kidney Injury; Adult; Age Factors; Glycogen; Humans; Influenza, Human; Male; Muscles; Myoglobinuria; Myositis; Necrosis

Explants of long-term cultures of nervous tissue of the rat cerebral cortex were placed for 30 min in a pure nitrogen atmosphere and then for 3--5 days transferred to the conventional cultivation co conditions. Electron microscope examinations showed that most severe changes occurred in the elements of oligodendroglia in the cytoplasm of which numerous lysosomes, large vacuoles, deposits of glycogen accumulated and myelin figures were formed. The damage of these cells appears to result in the degeneration of myelin sheaths. Edematous changes and glycogen accumulation were prevalent in astrocytes. Alongside with this, neurons had no such severe changes under these treatments. Its is emphasized that the intensity of reproducible oxygen deficiency must be taken into consideration in the evaluation of the sensitivity to anoxia of various nervous tissue elements.

Topics: Animals; Animals, Newborn; Cerebral Cortex; Culture Techniques; Glycogen; Histocytochemistry; Hypoxia, Brain; Microscopy, Electron; Myelin Sheath; Necrosis; Oligodendroglia; Rats; Time Factors

In mice poisoned by alpha-amanitin nuclear changes typical of this toxin were observed in beta-cells of pancreatic islets. The lesions became progressively more severe and at 48 h after toxin injection some cells were necrotic. The damage to these cells could have implications in the changes in glycogen metabolism which occur after alpha-aminitin poisoning.

Topics: Amanitins; Animals; Cell Nucleus; Glycogen; Islets of Langerhans; Male; Mice; Microscopy, Electron; Necrosis

Topics: Adenylyl Cyclases; Adolescent; Carnitine; Carnitine O-Palmitoyltransferase; Enflurane; Glycogen; Humans; Methyl Ethers; Muscles; Muscular Diseases; Myoglobinuria; Necrosis; Syndrome

Liver dysfunction following whole-body Co-60 irradiation has been studied in domestic and desert rat species. A significant elevation in the serum transaminases activity was noticed both in gerbil and house rat. Alkaline phosphatase and plasma cholesterol levels were also increased indicating an early radiation impairment of the liver tissue, which was later confirmed by histological studies. A steady fall in liver glycogen in irradiated gerbils was strikingly in contrast to an increase in irradiated house rat. Drastic depletion in liver glycogen, changes in the serum enzyme levels and the severity of the hepatic necrosis in gerbils point out that desert mammalian species are much more sensitive to radiation hazard as compared with domestic ones.

Topics: Alanine Transaminase; Alkaline Phosphatase; Animals; Aspartate Aminotransferases; Cholesterol; Gerbillinae; Glycogen; Liver; Liver Diseases; Necrosis; Radiation Effects; Radiation Injuries; Rats

The lethal dose of diphtheria toxin (IDLM per 1 kg of body weight) was injected to Chinchilla line adult rabbits. Histological and electron-microscopy investigations were carried out in time periods from 3 to 24 hours following the administration of the toxin. Degenerative and necrotic changes in the myocardial cells under conditions of the given experiment were not observed. In many muscular cells dilatation of the perinuclear spaces due to the thinning of the myofibrila layer moved to the periphery of the cell was noted. Electron-microscopy investigation of the perinuclear spaces showed a decrease in the number of mitochondria, reduction of the elements of sarcoplasmatic reticulum and disappearance of ribosomes. Cytochemically, in the opened cytoplasmatic matrix there were revealed numerous beta-granules of glycogen. In nuclei fragmentation of nucleoli with reduction of their granular component was observed. The changes described justify the conclusion that acute diphtheria intoxication at early stages of exposure to the toxin brings about impairment of the protein synthesis not only at the level of translation on cytoplasmatic ribosomes, as was suggested before, but at the level of ribosome formation in the nucleus as well.

Topics: Acute Disease; Animals; Diphtheria; Glycogen; Histocytochemistry; Male; Microscopy, Electron; Mitochondria, Muscle; Muscle Proteins; Myocardium; Myofibrils; Necrosis; Rabbits; Sarcoplasmic Reticulum

A case of benign clear cell tumor ("sugar tumor") of the lund with extensive necrosis is reported. Electron microscopic study established the diagnosis by virtue of the characteristic cytoplasmic membrane-bound glycogen. Ultrastructural study may be necessary in cases containing necrosis to differentiate this lesion decisively from metastatic renal cell carcinoma.

Topics: Adenocarcinoma; Aged; Cytoplasm; Diagnosis, Differential; Female; Glycogen; Humans; Lung Neoplasms; Necrosis; Neoplasm Metastasis

Facial nerve neurectomy were performed in the baboon (Papio papio). Histochemical investigations showed usual criteria of such lesions. Therefore a loose of glycogene within the Type I muscular fibers was observed in animals with a former facial spasm.

Topics: Adenosine Triphosphatases; Animals; Atrophy; Facial Muscles; Facial Nerve; Glycogen; Haplorhini; Necrosis; Nerve Degeneration; Papio; Photic Stimulation; Spasm

The inter-relationships of 32 pathologic and 7 clinical parameters encountered in the study of 1000 examples of invasive breast carcinoma have been presented. In some instances the biological significance of these associations is at present unclear. In others it is to be noted that there is no information provided as to the rank of their significance. Nevertheless, the associations that were encountered not only help further characterize the various forms of breast cancer but also provide information regarding the possible biological significance of some of their features. Although it is not our intention to minimize the possible significance of the inter-relationships of pathologic parameters, most emphasis in the summarizing statements which follow has been placed upon those correlations which may relate to prognosis. In this regard reference has been made to short-term treatment failure, vis a vis local recurrence and/or metastases, which may not necessarily accurately reflect patient survival, although generally such a relationship exists. Information in this regard as well as to the rank of the significance of these pathologic features shall be forthcoming when sufficient time has elapsed since the inception of this study to allow for such conclusions, i.e. survival or long-term treatment failure rates. Lastly, it becomes evident that the guidelines followed in the examination of these specimens appear to represent at least the minimum requirements necessary for a meaningful pathologic evaluation of breast carcinoma.

Topics: Adenocarcinoma, Mucinous; Adult; Blood Vessels; Breast Neoplasms; Calcium; Carcinoma; Carcinoma, Adenoid Cystic; Carcinoma, Intraductal, Noninfiltrating; Carcinoma, Papillary; Carcinosarcoma; Cell Nucleus; Connective Tissue; Elastic Tissue; Female; Glycogen; Histiocytes; Humans; Lymphatic Metastasis; Lymphocytes; Middle Aged; Mucins; Necrosis; Neoplasms, Multiple Primary; Paget's Disease, Mammary; Papilloma; Sweat Glands

Calcium antagonistic compounds including physiological ions of K and Mg are supposed to protect the heart against the deleterious effect of calcium overload. Pretreatment with K,Mg-aspartate in a single i.v. dose of 100 mg/kg was performed in dogs 5--10 min prior to isoproterenol chloride injection in a single dose of 7 mg/kh s.c. Administration of K,Mg-aspartate alone in the above-mentioned dose produced reversible changes of mitochondria after 2--6 hr. K,Mg-aspartate pretreatment applied prior to isoproterenol application revealed summarization of both K,Mg-aspartate and isoproterenol-produced changes after 2--6 h without significantly preventing hypoxic-like alterations. However, the final result after 24 h was good improvement of ultrastructure generally resembling metabolic regeneration and/or enhanced metabolic activity.

Topics: Animals; Aspartic Acid; Calcium; Dogs; Extracellular Space; Glycogen; Histocytochemistry; Isoproterenol; Lipids; Magnesium; Male; Mitochondria, Muscle; Myocardial Infarction; Necrosis; Potassium; Sarcoplasmic Reticulum

Although the effect of cold and heat stress on myocardial metabolisms has been widely studied, this parameter has not been investigated over a wide range of environmental temperatures after myocardial infarction. Since high as well as low temperatures are known to adversely affect the myocardium, changes in enviromental temperature are likely to be of great importance to patients suffering from acute coronary insult. Therefore, the myocardial metabolism was studied at different environmental temperatures in albino rats with isoproterenol-induced infarct-like myocardial necrosis. Male albino rats weighing 100 to 150 g were selected for the study. The investigations included ECG (lead II), histology, serum free fatty acids (FFA), serum triglycerides (TGS), cardiac noradrenaline, cardiac glycogen, and adrenal ascorbic acid, after the induction of myocardial necrosis. The biochemical changes were minimum between 10 and 15 degrees C while, at 4 degrees C, marked changes were observed. No significant change was seen in the serum triglycerides.

Topics: Adrenal Glands; Alanine Transaminase; Animals; Ascorbic Acid; Aspartate Aminotransferases; Cardiomyopathies; Fatty Acids, Nonesterified; Glycogen; Heart; Isoproterenol; Male; Myocardial Infarction; Myocardium; Necrosis; Norepinephrine; Organ Size; Rats; Temperature

In 23 healthy crossbred pigs of Yorkshire and Swedish Landrace (body weight 85 to 90 kg), stress was produced by pharmacological restraint. Cardiac lesions were observed in all the experimental animals, but no alterations were seen in the 9 controls. The lesions consisted of focal myocardial necrosis with infiltration of mononuclear inflammatory cells. Histochemical stains for two dehydrogenases, cytochrome oxidase and unspecific esterase, were applied to fresh-frozen sections of heart muscle. The damaged muscle fibers exhibited initially an increase in formazan deposits, and then a decrease and total loss of enzymatic activity. A reduction or total loss of glycogen and accumulation of lipids were demonstrated in the damaged myocardium ultrastructurally. The mitochondria were swollen with focal loss of the cristae. They often exhibited electron-dense of diverse appearance. In degenerating cells, the myofilaments usually lacked the normal cross-striations whereas, in necrotic foci, the changes ranged from clumping to complete lysis of the myofilaments. The sarcoplasmic reticulum and the T system contained numerous dilated vesicles in cells with mitochondrial and myofibrillar damage. It was concluded that the myocardial alterations, following restraint stress, were caused by a reflex liberation of cardiotoxic catecholamines.

Topics: Animals; Dihydrolipoamide Dehydrogenase; Female; Glycogen; L-Lactate Dehydrogenase; Male; Myocardium; Myofibrils; Necrosis; Stress, Physiological; Succinate Dehydrogenase; Swine

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Capillary Permeability; Cell Membrane; Cytoplasm; Dogs; Endoplasmic Reticulum; Extracorporeal Circulation; Glucose-6-Phosphatase; Glycogen; Hematocrit; Histocytochemistry; Humans; Hypoxia; Liver; Liver Circulation; Lysosomes; Mitochondria, Liver; Necrosis; Succinate Dehydrogenase

Topics: Animals; Cardiomyopathies; Catecholamines; Electron Transport Complex IV; Esterases; Glycogen; Heart; Lipid Metabolism; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Necrosis; Oxidoreductases; Sarcoplasmic Reticulum; Stress, Physiological; Swine

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Cold Temperature; Creatine; Fatty Liver; Fructose-Bisphosphate Aldolase; Glycogen; Hair; Hematocrit; Hemorrhage; Hypothermia; Isoenzymes; Kidney; L-Lactate Dehydrogenase; Leukocyte Count; Lipids; Liver; Liver Glycogen; Lung Diseases; Male; Muscles; Myocardium; Necrosis; Phosphotransferases; Rabbits; Time Factors

Topics: Adenosine Triphosphate; Animals; Glucose; Glycogen; Heart; Heart Diseases; Hypoxia; Isoproterenol; Lactates; Male; Myocardium; Necrosis; Perfusion; Phosphocreatine; Rats; Time Factors

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Anaerobiosis; Animals; Energy Metabolism; Gastric Mucosa; Glucosephosphates; Glycogen; Glycolysis; Ischemia; Lactates; Liver; Male; Muscles; Necrosis; Pyruvates; Rats; Shock, Hemorrhagic; Stomach Ulcer; Stress, Physiological

Topics: Animals; Anura; Endoplasmic Reticulum; Fasting; Fatty Liver; Glycogen; Inclusion Bodies; Lipids; Liver; Lysosomes; Microscopy, Electron; Mitochondria; Necrosis; Seasons; Starvation

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Blood Glucose; Blood Pressure; Creatine; Glycogen; Hindlimb; Ischemia; Lactates; Male; Muscles; Necrosis; Phosphocreatine; Rats; Time Factors; Tourniquets

Topics: Cataract; Cytoplasmic Granules; Endoplasmic Reticulum; Epithelial Cells; Glaucoma; Glycogen; Histocytochemistry; Humans; Lens, Crystalline; Male; Microscopy, Electron; Middle Aged; Necrosis

Topics: Animals; Anura; Biometry; Cilia; Epithelial Cells; Extraembryonic Membranes; Female; Glycogen; Histocytochemistry; Macrophages; Mucous Membrane; Necrosis; Oviducts; Ovulation; Periodicity; Pregnancy; Regeneration; Time Factors; Uterus

Topics: Cell Count; Cell Differentiation; Chromatin; Female; Gestational Age; Glycogen; Golgi Apparatus; Histocytochemistry; Humans; Ischemia; Microscopy, Electron; Mitochondria; Necrosis; Placenta; Placenta Diseases; Pregnancy; Regeneration; Rh-Hr Blood-Group System; Staining and Labeling

Topics: Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; Chemical and Drug Induced Liver Injury; Cold Temperature; Drug Tolerance; Glutamate Dehydrogenase; Glycogen; Histocytochemistry; Lipid Metabolism; Liver; Liver Diseases; Mice; Necrosis; Staining and Labeling; Time Factors

Topics: Abnormalities, Drug-Induced; Alkaline Phosphatase; Animals; Bone Matrix; Calcification, Physiologic; Calcium; Cartilage; Chick Embryo; Epiphyses; Glycogen; Glycosaminoglycans; Insulin; Minerals; Necrosis; Osteogenesis; Tarsal Bones; Tibia

Topics: Animals; Autoradiography; Cardiomegaly; Cell Nucleus; Chromatin; DNA; Edema; Glycogen; Histocytochemistry; Hypertrophy; Injections, Intraperitoneal; Isoproterenol; Male; Microscopy; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Necrosis; Rats; Ribosomes; RNA; Sarcoplasmic Reticulum; Time Factors

Topics: Animals; Carbon Dioxide; Cell Membrane; Cell Nucleus; Cytoplasmic Granules; Gases; Glycogen; Guinea Pigs; Heart Atria; Male; Methods; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Necrosis; Nitrogen; Nitrous Oxide; Oxygen; Ribosomes; Time Factors; Tissue Preservation; Xenon

Topics: Adolescent; Biopsy; Brain Chemistry; Cerebral Cortex; Frontal Lobe; Glycogen; Humans; Male; Microscopy, Electron; Necrosis; Neuroglia; Neurons; Synapses; Tuberous Sclerosis

Topics: Acute Disease; Animals; Brain; Cerebellum; Cerebral Cortex; Choroid Plexus; Glycogen; Hypertrophy; Inflammation; Macaca; Necrosis; Neuroglia; Protons; Radiation Dosage; Radiation Injuries, Experimental; Spinal Cord

Topics: Animals; Arterial Occlusive Diseases; Coronary Disease; Creatine Kinase; Dogs; Electrocardiography; Glycogen; Hyaluronoglucosaminidase; Myocardial Infarction; Myocardium; Necrosis; Spectrophotometry; Time Factors

Topics: Carcinoma, Squamous Cell; Cytodiagnosis; Diagnosis, Differential; Gingivitis, Necrotizing Ulcerative; Glycogen; Histocytochemistry; Humans; Mouth Mucosa; Mouth Neoplasms; Necrosis; Polysaccharides

Topics: Acid Phosphatase; Adrenal Glands; Animals; Chromaffin System; Cytoplasm; Depression, Chemical; Dogs; Fats; Femoral Artery; Glycogen; Glycosaminoglycans; Heart; Heparin; Histocytochemistry; Injections, Intra-Arterial; Intestine, Small; Kidney; Kidney Diseases; Leukocytes; Liver; Liver Glycogen; Lung; Mononuclear Phagocyte System; Muscles; Necrosis; Penicillins; Peritoneum; RNA; Spleen; Stimulation, Chemical; Stomach; Succinate Dehydrogenase

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Basement Membrane; Blood Vessels; Blood-Brain Barrier; Brain; Brain Edema; Capillaries; Cats; Cell Membrane; Cerebral Cortex; Extracellular Space; Gliosis; Glycogen; Histocytochemistry; Microscopy, Electron; Models, Neurological; Necrosis; Neuroglia; Oxidoreductases; Pinocytosis; Radiation Effects; Tetrazolium Salts; Time Factors; Ultraviolet Rays

Topics: Animals; Brain Edema; Brain Injuries; Cerebral Cortex; Cold Temperature; Endoplasmic Reticulum; Extracellular Space; Female; Glycogen; Inclusion Bodies; Male; Microscopy, Electron; Mitochondria; Necrosis; Neuroglia; Rats; Ribosomes

Topics: Animals; Cardiomyopathies; Collagen; Glycogen; Glycolysis; Hydroxyproline; Male; Myocardium; Necrosis; Norepinephrine; Phosphorus; Proline; Rabbits

Topics: Animals; Anterior Chamber; Aqueous Humor; Ciliary Body; Cornea; Electrocoagulation; Eye; Eye Diseases; Glucose; Glycogen; Iris; Ischemia; Lactates; Lens, Crystalline; Necrosis; Rabbits; Water

Topics: Animals; Glycogen; Heart; Hypotension, Orthostatic; Methods; Mitosis; Myocardial Infarction; Myocardium; Necrosis; Rabbits; Regeneration; Shock; Time Factors

Topics: Adult; Alcoholism; Aspartate Aminotransferases; Chronic Disease; Creatine Kinase; Fructose-Bisphosphate Aldolase; Glycogen; Humans; Hypokalemia; Male; Middle Aged; Muscles; Muscular Diseases; Necrosis; Potassium; Sodium

Topics: Adenosine Triphosphatases; Alcohol Oxidoreductases; Alkaline Phosphatase; Animals; Arginase; Aspartate Aminotransferases; Basophils; Bile Ducts, Intrahepatic; Chemical and Drug Induced Liver Injury; Connective Tissue; Cytoplasm; Esterases; Glutamate Dehydrogenase; Glutamates; Glycogen; Halothane; Horse Diseases; Horses; Liver; Necrosis; Staining and Labeling; Succinate Dehydrogenase

Topics: Anemia; Animals; Bile Ducts; Cell Division; Edema; Endoplasmic Reticulum; Female; Glycogen; Graft vs Host Reaction; Hepatic Veins; Histocompatibility; Infarction; Liver; Liver Transplantation; Methods; Mitochondrial Swelling; Necrosis; Phlebitis; Plasma Cells; Rats; Transplantation Immunology; Transplantation, Homologous

Topics: Animals; Cardiomyopathies; Dihydrolipoamide Dehydrogenase; Electron Transport Complex IV; Endoplasmic Reticulum; Epinephrine; Glycogen; Heart; Histocytochemistry; Lipids; Male; Microscopy, Electron; Mitochondria, Muscle; Myocardial Infarction; Myocardium; Myofibrils; NAD; NADP; Necrosis; Rats; Succinate Dehydrogenase; Transferases

Topics: Animals; Calcinosis; Cardiomyopathies; Disease Models, Animal; Endoplasmic Reticulum; Female; Glycogen; Histocytochemistry; L-Lactate Dehydrogenase; Microscopy, Electron; Mitochondria; Myocardium; Myofibrils; Necrosis; Nephrectomy; Parathyroid Glands; Rats; Succinate Dehydrogenase; Transferases; Uremia

Topics: Adrenal Cortex Hormones; Adrenalectomy; Animals; Atrophy; Blood Glucose; Diabetes Mellitus; Glycogen; Hyperglycemia; Hypoglycemia; Hypophysectomy; Insulin; Insulin Secretion; Islets of Langerhans; Liver Glycogen; Muscles; Myocardium; Necrosis; Rats; Staining and Labeling; Thyroidectomy; Thyroxine

Topics: Alkaline Phosphatase; Animals; Calcium; Cardiomyopathies; Digitoxin; Electron Transport Complex IV; Female; Glucosyltransferases; Glycogen; Histocytochemistry; Hypoxia; Lipid Metabolism; Necrosis; Oils; Papillary Muscles; Phosphates; Rats; Succinate Dehydrogenase; Water-Electrolyte Balance

Topics: Animals; Carbohydrates; Epinephrine; Glycogen; Heart Diseases; Histocytochemistry; Isoproterenol; Lysosomes; Male; Microscopy, Electron; Mitochondria; Myocardium; Myofibrils; Necrosis; Norepinephrine; Oxidoreductases; Phospholipids; Rats; Sarcoplasmic Reticulum

Topics: Acclimatization; Alanine Transaminase; Animals; Blood Glucose; Cold Temperature; Corticosterone; Glycerolphosphate Dehydrogenase; Glycogen; L-Lactate Dehydrogenase; Liver; Malate Dehydrogenase; Male; Muscular Diseases; Necrosis; Physical Exertion; Rats

Topics: Aflatoxins; Animals; Body Weight; Chemical and Drug Induced Liver Injury; Glycogen; Liver Diseases; Male; Necrosis; Rabbits; Skin Absorption; Time Factors

Topics: Animals; Brain Diseases; Cerebral Cortex; Cobalt; Dendrites; Glycogen; Histocytochemistry; Microscopy, Electron; Necrosis; Nerve Degeneration; Neuroglia; Rats

Topics: Aflatoxins; Animals; Aspergillus; Cytoplasm; Female; Glucosyltransferases; Glycogen; Kidney Tubules; Liver; Male; Mitochondria, Liver; Necrosis; Rats; Toxins, Biological

Topics: Animals; Calcium; Cats; Drug Synergism; Epinephrine; Female; Fluorine; Glycogen; Heart; Histocytochemistry; Hydrocortisone; Injections; Magnesium; Myocardium; Necrosis; Potassium; Rats; Sodium; Water-Electrolyte Balance

Topics: Animals; Cerebral Ventricles; Choroid Plexus; Cytoplasmic Granules; Fetus; Glycogen; Macrophages; Microscopy, Electron; Necrosis; Phagocytosis; Rats; Telencephalon

Topics: Adult; Conjunctiva; Cornea; Corneal Dystrophies, Hereditary; Cysts; Epithelium; Glycogen; Histological Techniques; Humans; Membranes; Microscopy, Electron; Necrosis; Staining and Labeling

Topics: Animals; Coronary Disease; Coronary Vessels; Dogs; Glycogen; Glycosaminoglycans; Histocytochemistry; Myocardium; Necrosis; Thoracic Arteries

Topics: Cell Division; Cytoplasm; Eye Neoplasms; Glioma; Glycogen; Humans; Melanoma; Necrosis

Topics: Adenine Nucleotides; Animals; Body Weight; Cholesterol; Creatine; Glycogen; Heart; Isoproterenol; Lactates; Myocardium; Necrosis; Organ Size; Phosphocreatine; Phospholipids; Propranolol; Rats; Triglycerides

Topics: Adolescent; Blood Chemical Analysis; Electromyography; Glycogen; Glycogen Storage Disease Type V; Histocytochemistry; Humans; Muscles; Muscular Diseases; Myoglobinuria; Necrosis; Pathology; Phosphotransferases; Physical Exertion; Regeneration; Rhabdomyolysis; Seizures

Topics: Artifacts; Carbohydrate Metabolism; Coloring Agents; Glycogen; Myocardium; Necrosis; Pathology; Rats; Research; Staining and Labeling

Topics: Coronary Disease; Electron Transport Complex IV; Electrons; Fluorescence; Glycogen; Heart Diseases; Histocytochemistry; Humans; Hypoxia; Isoproterenol; Lipids; Microscopy; Microscopy, Electron; Microscopy, Fluorescence; Mitochondria; Myocardial Infarction; Myocardium; Necrosis; Pathology; Rats; Research; Succinate Dehydrogenase

Topics: Coronary Circulation; Coronary Vessels; Electron Transport Complex IV; Glycogen; Histocytochemistry; L-Lactate Dehydrogenase; Leucyl Aminopeptidase; Monoamine Oxidase; Myocardial Infarction; Myocardium; Necrosis; Nucleotidases; Pathology; Phosphotransferases; Rats; Research; Succinate Dehydrogenase

Topics: Amidohydrolases; Antimalarials; Coronary Vessels; Electron Transport Complex II; Electron Transport Complex IV; Glycogen; Histocytochemistry; Methoxamine; Monoamine Oxidase; Morphogenesis; Myocardial Infarction; Myocardium; Necrosis; Nucleotidases; Phosphotransferases; Rats; Research; Succinate Dehydrogenase; Toxicology