BACKGROUND: Although cardiac hypertrophy contributes to cardiac failure, the underlying mechanism has not yet been precisely determined. This study was planned in order to determine the pathogenesis of heart failure following cardiac hypertrophy induced by -adrenergic stimulation. METHODS: The extent of cardiac hypertrophy was assessed after administrating isoproterenol (ISO, 5 mg/kg) intraperitoneally for 6 hours, 1, 3, 5, 7 and 10 days. The hematoxylin-eosin, Masson's trichrome and phosphotungstic acid hematoxylin stains along with immunohistochemical stainings for proliferating cell nuclear antigen and Ki-67 were performed in the paraffin-embedded left ventricle sections. Apoptosis was assessed by DNA laddering and terminal deoxynucleotidyl transferase TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay. TUNEL positive myocytes and some nonmyocytes appeared in the subepicardium at 6 hours after ISO administration. The localization of these cells was shifted to the subendocardium within 24 hours, and the TUNEL positive cells were seen throughout the myocardium on the 5th day after ISO treatment. Necrotic myocyte death occurred on the 3rd day of ISO administration in the subendocardium, and initial pericellular fibrosis was followed and increased thereafter, with replacement fibrosis accompanied by further necrotic myocyte cell death. CONCLUSIONS: Our data showed that ISO treatment induced apoptotic myocyte death and superimposed necrotic myocyte death with subsequent fibrosis. The observed cardiac myocyte death may reflect myocardial dysfunction.
Animals ; Apoptosis ; Cardiomegaly* ; Cell Death* ; Coloring Agents ; DNA ; DNA Nucleotidylexotransferase ; Fibrosis ; Heart Failure ; Heart Ventricles ; Hematoxylin ; Hypertrophy ; In Situ Nick-End Labeling ; Isoproterenol ; Muscle Cells ; Myocardium ; Myocytes, Cardiac* ; Phosphotungstic Acid ; Proliferating Cell Nuclear Antigen ; Rats*

Brain ischemia leads to overstimulation of N-methyl-D-aspartate (NMDA) receptors, referred as excitotoxicity, which mediates neuronal cell death. However, less attention has been paid to changes in synaptic activity and morphology that could have an important impact on cell function and survival following ischemic insult. In this study, we investigated the effects of reperfusion after oxygen/glucose deprivation (OGD) not only upon neuronal cell death, but also on ultrastructural and biochemical characteristics of postsynaptic density (PSD) protein, in the stratum lucidum of the CA3 area in organotypic hippocampal slice cultures. After OGD/reperfusion, neurons were found to be damaged; the organelles such as mitochondria, endoplasmic reticulum, dendrites, and synaptic terminals were swollen; and the PSD became thicker and irregular. Ethanolic phosphotungstic acid staining showed that the density of PSD was significantly decreased, and the thickness and length of the PSD were significantly increased in the OGD/reperfusion group compared to the control. The levels of PSD proteins, including PSD-95, NMDA receptor 1, NMDA receptor 2B, and calcium/calmodulin-dependent protein kinase II, were significantly decreased following OGD/reperfusion. These results suggest that OGD/reperfusion induces significant modifications to PSDs in the CA3 area of organotypic hippocampal slice cultures, both morphologically and biochemically, and this may contribute to neuronal cell death and synaptic dysfunction after OGD/reperfusion.
Brain Ischemia ; Cell Death ; Dendrites ; Endoplasmic Reticulum ; Ethanol ; Mitochondria ; N-Methylaspartate ; Neurons ; Organelles ; Phosphotungstic Acid ; Post-Synaptic Density ; Presynaptic Terminals ; Protein Kinases ; Proteins ; Receptors, N-Methyl-D-Aspartate ; Reperfusion

Eighteen cases of osteonecrosis of the femoral head associated with macromolecular polyvinylpyrrolidone (PVP) deposition were analysed on the basis of clinical, radiologic and pathologic features. The cases were observed during 8 years period from January, 1974 to December, 1981. The pathogenesis of the osteonecrosis of the femoral head due to PVP storage in reticuloendothelial system were discussed in detail. Parenteral administration of high-molecular PVP in repeated, long duration led to osteonecrosis of the femoral head. Storage of PVP in the histiocytes of the bone marrow resulted in osteonecrosis of the femoral head followed by microciculation disturbance. PVP-induced osteonecrosis were manifested as multiple foci of necrosis involving not only the femoral head, other long bones around joints, but also the visceral reticuloendo-thelial system characterized by infiltrates of histiocytes laden with PVP. The patients with PVP induced osteonecrosis complianed multiple joint pain in their early course of the disease. On roentgenogram, osteonecrosis were often noted in the hip, shoulder, knee, and ankle in order or frequency. Foamy histiocytes laden with PVP were characteristic on hematoxylin-eosin stain diagnostic on Weigert's elastica, phosphotungstic acid hematoxylin, and Congo red stains. As far as rationale of the treatment concerning a number of staging systems for Osteonecrosis, the choice of surgical procedures were similar to those given by W.F. Enneking et al. In the series, we have performed two hips in total surface replacement, 26 hips in total hip replacement mostly for 3rd generation-configuration of Charnley prosthesis. In addition, one case for free vascularized fibula graft and trans-trochanteric rotational osteotomy after Sugioka were also included for this study. The result of treatment was rather optimistic. However, complications have occured in 4 hips of 3 patients which required removal of whole prosthetic components. Therefore, we underwent revisional surgery in three out of four hips subsequently during the short post-poerative follow-up. These will be published in the future.
Ankle ; Arthralgia ; Arthroplasty, Replacement, Hip ; Bone Marrow ; Coloring Agents ; Congo Red ; Fibula ; Follow-Up Studies ; Head ; Hematoxylin ; Hip ; Histiocytes ; Humans ; Joints ; Knee ; Mononuclear Phagocyte System ; Necrosis ; Osteonecrosis ; Osteotomy ; Phosphotungstic Acid ; Povidone ; Prostheses and Implants ; Rubber ; Shoulder ; Transplants