Initiation Of Necrosis Research Articles

Cardioprotective use of melatonin causes gender-specific changes of vegetative cardiac control in a setting of constant illumination

The aim of the work was to assess gender-specific differences in vegetative cardiac control with development of myocardial necrosis in a setting of constant illumination and use of melatonin. An experiment in mature laboratory breed albino rats of either sex simulated abnormal lighting regime. The simulation included keeping the animals for 10 days under constant illumination of 500 lux. On Day 11, myocardial necrosis (MN) was modeled by administering adrenaline (0.5 mg/kg intramuscularly); a follow-up electrocardiography was performed at 1 hour and 24 hours later to assess for heart rhythm variability. A half of animals was given melatonin 1 hour prior to MN modeling (5 mg/kg intraperitoneally). The animals kept under day/night balance were used as controls. The results have shown constant illumination to cause gender-specific changes in effects of vegetative nervous system on formation of heart rhythm in rats; the activity of the parasympathetic component increased in females and decreased in males. In females, the development of adrenaline-induced myocardial necrosis in a setting of constant illumination was accompanied by changes in cardiac interval (cardiointervalography) findings. The development of these changes with time was identical to that in day/night balance, with a more pronounced activity of the parasympathetic component and a synergetic enhancement of the sympathetic component. When exposed to constant illumination, males had a response different from that in day/night balance; their response to constant illumination was characterized by reduced activity of the parasympathetic component and by predominance of the sympathetic component. Cardioprotective use of melatonin was shown to increase parasympathetic tone compared to day/night balance; in males, this increase was evident at initiation of necrosis and in females, the increase was seen at the peak of necrotic foci formation in the myocardium.

Histopathological and Biochemical study of the effect of Citrullus colocynthis on the heart and liver of mature male rabbits: as a model for mammals

The aim of the present work is to found out if there are histopathological and enzymatic effects on the heart and liver after oral administration of Citrullus colocynthis (CC) fruit (bitter apple) for mature male rabbits, as a model for mammals. Two experiments were performed for sixty mature male rabbits that equally and randomly divided into six groups each containing five animals .In the two experiments ,independently, three groups in each one were considered as treated groups and represented as T1, T2 and T3 groups .These rabbits groups were orally administrated with low dosage of CC (4.8mg/kg/day,experiment No.1 ) and double dosage of CC extract (9.6mg /kg /day , experiment No2 ) for three intervals 2, 4 and 8 weeks ,respectively. The other three groups in each experiment were considered control and represented as C1, C2 and C3 groups, respectively. All the rabbits in control groups were given orally distilled water (DW) at the same periods of treated groups. Histopathological changes of the heart and liver with related enzymes namely; serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and creatinine kinase (SCK) were studied.The histopathological study revealed no changes in rabbit’s heart tissue particularly after treatment with 4.8mg/kg/day of CC for 2 and 4 weeks. While no histopathological changes were observed in the heart of rabbit groups treated with 9.6mg/kg/day of CC extract after 2 weeks. The results of the treatment with the two dosages of the CC for 8 weeks indicated a mild degenerative changes and mild necrosis of the myocardial cells. There was swelling of the hepatocytes and perivascular cuffing of mononuclear inflammatory cells after two weeks of daily treatment with 4.8mg/kg/day of CC exposure. After four weeks with the low dosage of the CC extract, caused initiation of necrosis, more inflammation picture of liver portal tract with sinusoid All rabbit groups showed statistically a significant gradual increase (P<0.05) in the value of serum enzyme GOT, GPT and CK levels after treatment with the two dosages of CC at the end of each different period compared with before treatment and control group. Concluded from this study that the dosage 4.8mg/Kg/day of CC plant resulted in simple histopathological effects on the heart and mild histopathological changes on the liver during the entire period of the study, instead of serum enzymatic elevation of SGOT ,SGPT and SCK. Further studies are recommended to found out the possibility to use and effects of CC on animal hygiene and reproduction

Endocytosis and intracellular trafficking contribute to necrotic neurodegeneration inC. elegans

Unlike apoptosis, necrotic cell death is characterized by marked loss of plasma membrane integrity. Leakage of cytoplasmic material to the extracellular space contributes to cell demise, and is the cause of acute inflammatory responses, which typically accompany necrosis. The mechanisms underlying plasma membrane damage during necrotic cell death are not well understood. We report that endocytosis is critically required for the execution of necrosis. Depletion of the key endocytic machinery components dynamin, synaptotagmin and endophilin suppresses necrotic neurodegeneration induced by diverse genetic and environmental insults in C. elegans. We used genetically encoded fluorescent markers to monitor the formation and fate of specific types of endosomes during cell death in vivo. Strikingly, we find that the number of early and recycling endosomes increases sharply and transiently upon initiation of necrosis. Endosomes subsequently coalesce around the nucleus and disintegrate during the final stage of necrosis. Interfering with kinesin-mediated endosome trafficking impedes cell death. Endocytosis synergizes with autophagy and lysosomal proteolytic mechanisms to facilitate necrotic neurodegeneration. These findings demonstrate a prominent role for endocytosis in cellular destruction during neurodegeneration, which is likely conserved in metazoans.

Serum withdrawal induces a redistribution of intracellular gelsolin towards F-actin in NIH 3T3 fibroblasts preceding apoptotic cell death

The intracellular distribution of gelsolin in NIH 3T3 cells was examined by immunostaining using affinity-purified polyclonal gelsolin antibodies before and after induction of apoptosis by serum withdrawal. Serum deprivation induced detachment of an increasing number of NIH 3T3 cells, but also apoptosis in attached cells as verified morphologically by chromatin condensation, nuclear fragmentation and labelling of their periphery by FITC-annexin V. Ongoing apoptosis was also demonstrated by activation of caspase-3 activity and chromatin cleavage into high-molecular-mass fragments, although no internucleosomal chromatin degradation (DNA-ladder formation) was detected. When cells were maintained in the presence of 10% foetal calf serum, gelsolin immunoreactivity was evenly distributed in the cytoplasm. No obvious co-localisation of gelsolin and the actin-containing stress fibres was detected under these conditions. At day one after serum withdrawal, a redistribution of gelsolin to actin filaments was detected within a few attached cells by double fluorescence staining. The number of cells exhibiting this redistribution increased at days two to four. In addition, the stress fibres increased in thickness and their length was continuously reduced. At day four, many cells contained shortened stress fibres, which had lost their longitudinal orientation. Additionally, the cytoplasm of a number of attached cells was highly condensed around their nuclei and a homogenous distribution of both gelsolin and actin was detected in the remaining cytoplasmic rim. Up to day two, these effects were reversible after re-addition of serum to attached cells. A similar redistribution of gelsolin immunore-activity was observed after induction of apoptosis by cycloheximide, but not after initiation of necrosis by hydrogen peroxide. In NIH 3T3 cells no alteration in the expression of gelsolin at the level of protein (Western blot) or specific mRNA (Northern blot) was observed after serum withdrawal. Using Western blotting, no proteolysis of gelsolin was detected up to day 4, although caspase-3 activity was found to have increased fivefold after serum withdrawal. These results suggested that in these cells F-actin severing might occur in the absence or advance of gelsolin cleavage by caspases. Intact gelsolin on its own may be sufficient for the dissolution of the microfilaments, since micro-injection of gelsolin into primary bovine lens cells led to a transient disappearance of the stress fibres and to a reduction of their attachment area to the substratum. In NIH 3T3 cells similar effects of micro-injected gelsolin were only observed at day one after serum withdrawal.

Cytological expression of early response to infection by Heterodera glycines Ichinohe in resistant PI 437654 soybean

The soybean PI 437654 is resistant to all known races of the soybean cyst nematode (SCN) in the U.S.A. and became a new source of resistance genes in cultivar development. Race 3, a wide-ranging nematode pathotype, was used to examine root cells of PI 437654 and susceptible 'Essex', 2, 3, and 5 days after inoculation (DAI). In initial response to SCN, both genotypes formed syncytia by cell wall dissolutions. Hypertrophy of syncytium component cells and hyperplasia of cells near syncytia were observed. At 2 DAI, incompatible response of PI 437654 to SCN was exhibited: limited cell hypertrophy, inhibition of syncytium growth, initiation of necrosis, and wall appositions. At 3 DAI, cellular events appeared to be a sum of the operative mechanisms for SCN resistance: irregular wall thickening, pronounced wall appositions, necrosis, and nuclear breakdown followed by cytoplasmic collapse. The cells surrounding the syncytia showed necrosis, wall apposition, and accumulation of electron-dense bodies. By 5 DAI, syncytia and neighboring cells were totally devoid of ground plasma and the degeneration process was completed. The normal route for early syncytium development in 'Essex' (increased number of organelles, intense vacuolization, accumulation of dense deposits in vacuoles, and wall ingrowths) suggests the involvement of portions of the developmental pathway of differentiating tissues in organogenesis. Early onset of SCN resistance 2 DAI in PI 437654 suggests rapid activation of genes in a cascade reaction leading to cell death. Key words : soybean, nematode, syncytium, cell death.

Immunochemotherapy in human hepatocellular carcinoma using the streptococcal agent OK-432.

Twenty-one patients with nonresectable hepatocellular carcinoma (HCC) received intraarterial infusion chemotherapy of Adriamycin (Adria Laboratories, Columbus, Ohio) via an indwelling catheter in the hepatic artery. Additional intratumoral injection therapy of OK-432 (50 KE) was administered to ten of these 21 patients. Nine of the ten patients showed a remarkable decrease in lymphocyte count on the first day after therapy. In all of the patients with a decreased lymphocyte count, computed tomograms (CTs) demonstrated evidence of necrosis associated with a rapid decrease in alpha fetoprotein (alpha-FP). Blastogenesis of lymphocytes in peripheral blood induced by phytohemagglutinin (PHA) increased by 3.99 +/- 1.9 (mean +/- SE) times 4 weeks after therapy. On the basis of these results, we concluded that intratumoral injection therapy of OK-432 apparently produced initiation of necrosis in HCC by cell-damaging activity as well as by improvement of cell-mediated immunity.

An electron microscopic study of liver cell necrosis due to albitocin

Liver cell necrosis produced in rats by injection of the triterpenoid glycoside albitocin was studied with the electron microscope. Coagulative necrosis was of two distinct types. The first was characterized by the presence of clumps of calcium-associated, electron-opaque granules in the matrix of mitochondria, the changes closely resembling those described in necrosis due to various other toxins. However, in the second, clumps of matrix granules were absent and the appearances were like those seen in ischaemic necrosis and in in vitro autolysis. It is probable that this second type of necrosis resulted from sinusoidal obstruction, which followed the development of the first type of necrosis in the peripheral parts of the lobules. Mitochondria1 abnormalities provided the best indication of the development of coagulative necrosis, but the findings cast doubt on the importance of calcium accumulation within mitochondria as a causative factor in the initiation of necrosis. Shrinkage necrosis involved cellular condensation followed by fission into multiple, membrane-bounded cytoplasmic fragments. Some of these were ingested by parenchymal cells and histiocytes. Others probably underwent a process akin to coagulative necrosis.