Evidence has indicated that low doses of anti-tumor regimens can induce cell apoptosis in vitro, although different regimens induce apoptosis by different mechanism and pathway. In recent years, new tumor treatment strategy has been mainly focused on inducing tumor cell apoptosis. The present review discusses the advantages and disadvantages of inducing tumor cell apoptosis. The benefit of inducing apoptosis is not to cause inflammatory reaction, but as its disadvantage, it inhibits immune responses, and the phagocytosis of apopotic bodies may result in horizontal transfer of genes (including oncogenes and other oncogenic materials), which can be one of the causes of tumor relapse. This paper proposes that the tumor treatment strategy should be turn into promoting tumor cell necrosis and inducing anti-tumor immune responses.
Antineoplastic Agents ; therapeutic use ; Apoptosis ; drug effects ; Humans ; Necrosis ; chemically induced ; Neoplasms ; drug therapy ; immunology ; pathology

Actins ; analysis ; Animals ; Dimethylnitrosamine ; Immunohistochemistry ; Liver ; metabolism ; pathology ; Male ; Necrosis ; chemically induced ; pathology ; Rats ; Rats, Wistar ; Reticulin ; analysis ; Silver Staining

A 63-year-old woman was admitted due to right upper quadrant abdominal pain. She was going through hemodialysis due to end stage renal disease and taking calcium polystyrene sulfonate orally and rectally due to hyperkalemia. Colonoscopy showed a circular ulcerative mass on the proximal ascending colon. Biopsy specimen from the mass showed inflammation and necrotic debris. It also revealed basophilic angulated crystals which were adherent to the ulcer bed and normal mucosa. These crystals were morphologically consistent with calcium polystyrene sulfonate. She was diagnosed with calcium polystyrene phosphate induced colonic necrosis and improved with conservative treatment.
Colonic Diseases/chemically induced/complications/*pathology ; Colonoscopy ; Female ; Humans ; Kidney Failure, Chronic/complications/*diagnosis ; Middle Aged ; Necrosis ; Polystyrenes/*adverse effects

OBJECTIVETo observe the pathological changes in the blood vessels in rabbit femoral head with glucocorticoid-induced necrosis and investigate the pathogenesis of glucocorticoid-induced osteonecrosis.

METHODSTwenty New Zealand white rabbits were randomly divided into two groups, namely group A. which was injected with horse serum and prednisone and group B as the control group. Chinese ink was injected into the femoral cavity of the rabbits to observe the blood vessels in the femoral head under optical microscope and the femoral head was examined histopathologically.

RESULTSCompared with the normal control group, the rabbits in group A had significantly decreased number of perfused vessels, which was featured by defective perfusion, osteocytie pyknosis or necrosis, increase of empty ostoocyte lacunae and fat cells, decrease of hematopoietic tissue, and blood vessel occlusion.

CONCLUSIONVascular occlusion and vasculitis due to glucocorticoid treatment may cause avascular necrosis of the femoral head.

Animals ; Blood Vessels ; pathology ; Female ; Femur Head ; blood supply ; pathology ; Femur Head Necrosis ; chemically induced ; pathology ; Male ; Prednisolone ; Rabbits ; Random Allocation ; Vasculitis ; pathology

Colonic necrosis is known as a rare complication following the administration of Kayexalate (sodium polystryrene sulfonate) in sorbitol. We report a rare case of colonic mucosal necrosis following Kalimate (calcium polystryrene sulfonate), an analogue of Kayexalate without sorbitol in a 34-yr-old man. He had a history of hypertension and uremia. During the management of intracranial hemorrhage, hyperkalemia developed. Kalimate was administered orally and as an enema suspended in 20% dextrose water to treat hyperkalemia. Two days after administration of Kalimate enema, he had profuse hematochezia, and a sigmoidoscopy showed diffuse colonic mucosal necrosis in the rectum and sigmoid colon. Microscopic examination of random colonic biopsies by two consecutive sigmoidoscopies revealed angulated crystals with a characteristic crystalline mosaic pattern on the ulcerated mucosa, which were consistent with Kayexalate crystals. Hematochezia subsided with conservative treatment after a discontinuance of Kalimate administration.
Adult ; Colon/*pathology ; Gastrointestinal Hemorrhage/etiology ; Humans ; Hyperkalemia/drug therapy ; Intestinal Mucosa/*pathology ; Male ; Necrosis/*chemically induced/complications/pathology ; Polystyrenes/*adverse effects/therapeutic use ; Uremia/*physiopathology

To study the mechanism of endotoxin-induced hepatocellular injury in rats, a single dose of endotoxin, 15mg/kg, was injected intraperitoneally with or without dexamethasone pretreatment. Studies included light microscopic, histochemical, and electron microscopic observations with concomitant assay of free acid phosphatase activity of liver homogenateg. The results showed an increase of acid phosphatase activity as early as 30 minutes after the injection of endotoxin, and by light microscopy random focal necrosis of liver cells at 1 hour and fibrin thrombi formation in sinusoids especially within the area of necrosis at 3 hours. However, ultrastructural alteration was noted as early as 5 minutes after the injection of endotoxin characterized by marked dilatation of RER. The degree of necrosis, fibrin thrombus formation, and the elevation of free acid phosphatase activity in the liver homogenates seemed to parallel each other suggesting a possible interrelationship among these phenomena. However, the ultrastructnral changes of the hepatocytes were present far ahead of the appearance of fibrin thrombi formation. Therefore, the causal relationship of the fibrin thrombi to liver cell injury appeared unlikely. Despite the increase of free acid phosphatase activity in liver homogenates, no demonstrable structural disruption of lysosomal membrane was noted. In view of the prominent changes of RER 5 minutes after the endotoxin administration, the primary injurious effect of endotoxin affects the membrane system of all organelles including the lysosomal membrane, leading to the leakage of lysosomal enzymes into the cytoplasmic sap. Dexamethasone pretreatment alleviated necrosis and markedly inhibited fibrin thrombus formation, and the mechanism of this effect is considered to be a stabilizing effect of glucocorticoid upon membrane systems.
Acid Phosphatase/metabolism ; Animal ; Endotoxins* ; Injections, Intraperitoneal ; Liver/enzymology ; Liver/pathology* ; Liver Diseases/chemically induced ; Liver Diseases/metabolism ; Liver Diseases/pathology* ; Male ; Necrosis ; Rats

OBJECTIVETo study the role of tumor necrosis factor-alpha (TNFalpha) on enterocyte apoptosis in the experimental model of fulminant hepatic failure (FHF).

METHODSLiver damage was induced by lipopolysaccharide (LPS)/TNFalpha in D-galactosamine (GalN) sensitized BALB/c mice. Serum TNFalpha levels were determined by enzyme-linked immunosorbent assays (ELISA). The intestinal tissues were studied micro- and ultra-microscopically at 2 h, 6 h, 9 h, 12 h and 24 h time points in mice with fulminant hepatic failure. Enterocyte apoptosis was determined by TUNEL method. The TNFR I expression in the intestinal tissue was tested by immunohistochemistry.

RESULTS(1) Gut mucosa was morphologically normal at every time point in all groups, but typical apoptotic cells could be seen in the experimental groups under the electron microscope. Apoptosis rate of gut mucosal epithelial cells was significantly increased at 6 h (large intestine: 6.47e(-3)+/-2.91e(-4); small intestine: 6.64e(-3)+/-3.78e(-4)), 9 h (large intestine: 6.81e(+4)+/-7.41e(+3); small intestine: 2.58e(+4)+/-2.28e(+3)) and 12 h (large intestine: 4.92e(+4)+/-9.80e(+3); small intestine: 5.24e(+4)+/-3.01e(+3)), and peaked at 12 h in mice with FHF. (2) TNFalpha induced apoptosis of enterocytes in mice with FHF. Anti-TNFalpha inhibited this effect. (3) The integrated OD (IOD) levels of TNFalpha receptor I protein expressed differently in the intestine of mice with GalN/LPS and GalN/ TNFalpha-induced FHF at 9 h after GalN/LPS and GalN/ TNFalpha administration, in comparison with those of the control groups. IOD level of TNFRI changed significantly at 6 h (large intestine: 2.82e(+4)+/-4.60e(+3); small intestine: 1.14e(+4)+/-2.13e(+3)), 9 h (large intestine: 6.81e(+4)+/-7.41e(+3); small intestine: 2.58e(+4)+/-2.28e(+3)) and 12 (large intestine: 4.92e(+4)+/-9.80e(+3); small intestine: 5.24e(+4)+/-3.01e(+3)) hours after GalN/LPS and GalN/ TNFa administration. The expression of TNFR1 protein was significantly higher at 9 and 12 h after GalN/LPS and GalN/TNFa administration than other time points. Protein expression of TNFR1 was positively correlated with enterocyte apoptosis.

CONCLUSIONTNFa can induce enterocyte apoptosis in mice with FHF. Anti- TNFalpha IgG can inhibit this role. Excessive TNFRI expression of enterocyte in fulminant hepatic failure can be induced by TNFa, which suggests that TNFalpha can induce apoptosis of enterocyte by up-regulation of TNFRI protein expression.

Animals ; Apoptosis ; physiology ; Enterocytes ; pathology ; Galactosamine ; Lipopolysaccharides ; Liver Failure, Acute ; chemically induced ; pathology ; Mice ; Mice, Inbred BALB C ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo evaluate and compare the histopathology effects and mechanisms of the methods of "invigorating spleen to remove phlem & promoting blood circulation to remove meridian obstruction" and "invigorate the kidney & promoting blood circulation to remove meridian obstruction" preventing hormone induced femoral head necrosis in hens.

METHODSSixty-four healthy hens were randomly divided into 4 groups: blank control group, model group, Jianpi group (with therapeutics of invigorating spleen to remove phlem), Bushen group (with the effect of warming kidney for duresis). All hens were injected intramuscularly with Medrat once a week for 16 weeks but normal saline in blank control group. Bilateral femoral heads were dissected on 8 weeks or 16 weeks. Paraffin tissue sections were prepared to detect histopathologic change with hematoxylin and eosin, or mason staining.

RESULTSHistological analysis showed that Huogu recipe I and Huogu recipe II can promote osteogenesis and repair osteonecrosis, increase blood circulation of bone marrow, and inhibit pimelosis of bone marrow. Compared with blank control group, the areas of adipose cells increased significantly (t = -12.9, P < 0.01), the area of immature collagen increased significantly (t = -2.0, P < 0.05) and the ratio of empty lacuna in medullary cavity (t = -3.7, P < 0.05). Compared with model group, both the area of adipose cells and the ratio of empty lacuna decreased in Jianpi group and Bushen group (F = 26.8, 13.5, P < 0.01), so it was with the Bushen group immature collagen (F = 4.6, P < 0.01).

CONCLUSIONBoth the methods of "invigorating spleen to remove phlem & promoting blood circulation to remove meridian obstruction" and "invigorate the kidney & promoting blood circulation to remove meridian obstruction" can prevent hormone induced femoral head necrosis. The time taking effect in the method of "invigorating spleen to remove phlem" was shorter.

Animals ; Chickens ; Drugs, Chinese Herbal ; Female ; Femur Head ; pathology ; Femur Head Necrosis ; chemically induced ; drug therapy ; pathology ; Glucocorticoids ; adverse effects ; Medicine, Chinese Traditional

OBJECTIVETo investigate the morphological changes and regeneration mechanism of sinusoidal endothelial cell.

METHODSSixty male Wistar rats (bought from SLC company limited of Japan) were divided into three groups. Fifty of them belonged to experiment group, five rats belonged to untreated group, and the rest five ones belonged to normal saline treated group. The experiment group was then divided into ten subgroups. All the rats of the experiment group were killed under anaesthesia using aether at 12, 24, 36 hrs, and 2, 3, 5, 7, 8, 10 and 14 days subsequently after an one-off injection of dimethylnitrosamine (DMN) (50 mg/kg). The liver tissues, bone marrows and peripheral blood of the rats were taken out rapidly. All the tissues received with HE staining, immunohistochemistry staining and double immunofluorescence labelings, and they were observed under a light microscope and electron microscope. The livers, bone marrows and peripheral blood from the rats at 24 hrs to 14 days after an injection of DMN were examined by light microscopic, immunohistochemical, and ultrastructural methods.

RESULTSSmall focal necrosis of the liver tissues was found at 12 hrs after the DMN injection, and gradually becomes more obvious from the 24 hrs. The most obvious necrosis, with lots of ED-1 (monocyte/phagocyte marker of rats) positive cells infiltration, was observed at 36 hrs. On the 2nd day and 3rd day after injection, the necrotic fragments and red cells were phagocyted by ED-1 positive macrophages. On the 5th day, some of the ED-1-positive cells were transformed from round to spindle in shape. On the 7th day, these cells contacted with residual reticulin fibers and became positive for SE-1, a marker of hepatic sinusoidal endothelial cells and Tie-1, an endothelial cell-specific surface receptor, associated with frequent occurrence of ED-1/SE-1 and ED-1/Tie-1 double positive spindle cells. On the 8th day, the histomorphology of liver tissue was similar with that on day 7, except that the range of the lesions had become smaller. On the 10th day, the regeneration of liver tissue increased, filling in the necrosis. On the 14th day, the necrotic tissues were almost replaced by regenerated liver tissues and thin bundles of central-to-central bridging fibrosis. 12 hrs after the DMN injection, bone marrow studies showed an increase in the number of ED-1 positive mononuclear cells, some of which were both BrdU/ED-1 positive. The number of ED-1 positive mononuclear cells reach their highest level at 36 hrs. These cells are morphologically similar to round mononuclear cells in bone marrows and could be found in the peripheral blood from 24 hrs to the 10 days. They reached their highest level in peripheral blood at the same time as in the bone marrow. These cells morphologically resembled ED-1 positive cells in necrotic tissues of the liver.

CONCLUSIONSThese findings suggest that round mononuclear ED-1-positive cells proliferate first in the bone marrow after DMN treatment, reach necrotic areas of livers through circulation, and differentiate to sinusoidal endothelial cells. Namely, hepatic sinusoids in DMN-induced necrotic areas may partly be reorganized possibly by vasculogenesis.

Animals ; Chemical and Drug Induced Liver Injury ; pathology ; Dimethylnitrosamine ; Endothelial Cells ; pathology ; ultrastructure ; Liver ; blood supply ; metabolism ; pathology ; ultrastructure ; Liver Regeneration ; Male ; Necrosis ; chemically induced ; pathology ; Neovascularization, Physiologic ; Rats ; Rats, Wistar

OBJECTIVETo evaluate the therapeutic effect of Compound Xuanju Capsule (CXC) on autoimmune prostatitis in rat models.

METHODSSixty healthy male Wistar rats were randomly divided into five groups of equal number: blank control, low-concentration purified prostate protein (low-conc PPP), low-conc PPP + CXC treatment, high-concentration PPP (hi-con PPP), and hi-conc PPP + CXC treatment. Autoimmune prostatitis models were established by intragastric administration of PPP solution at 15 mg/ml (low concentration) and 80 mg/ml, respectively. At 30 days after modeling, the rats in the blank control and low-conc and hi-conc PPP model groups were treated with normal saline, and those in the other two groups with CXC at a daily dose of 0.068 g/ml. At 30, 45, and 60 days, all the animals were sacrificed for observation of pathological changes in the prostate tissue and determination of the levels of IL-8, IL-10, and TNF-alpha in the serum.

RESULTSCompared with the PPP models, the hi-conc PPP + CXC group showed significantly reduced levels of IL-8 and TNF-alpha in the serum at 45 days ([148.54 +/- 17.23] and [62.14 +/- 5.59] pg/ml vs [100.77 +/- 11.08] and [32.63 +/- 2.91] pg/ml, P < 0.05) and at 60 days ([143.69 +/- 17.28] and [59.38 +/- 5.50] pg/mlvs [95.77 +/-10.53] and [29.63 +/- 2.66] pg/ml, P < 0.05), and so did the low-cone PPP + CXC group at 45 days ([128.47 +/- 12.21] and [40.43 +/- 3.64] pg/ml vs [111.76 +/- 10.07] and [35.44 +/- 3.17] pg/ml, P < 0.05) and at 60 days ([131.07 +/- 10.93] and [43.34 +/- 3.91] pg/ml vs [97.46 +/- 8.75] and [30.44 +/- 2.75] pg/ml, P < 0.05). The serum level of IL-10 was remarkably elevated in the hi-cone PPP + CXC group as compared with that of the PPP models at 45 and 60 days ([189.14 +/- 16.78] and [184.14 +/- 15.89] pg/ml vs [230.48 +/- 29.96] and [248.48 +/- 31.03] pg/ml, P < 0.05), and so was it in low-cone PPP + CXC group ([223.14 +/- 17.87] and [224.14 +/- 17.93] pg/ml vs [231.42 +/- 23.18] and [249.42 +/- 24.97] pg/ml, P < 0.05). Pathological examination revealed morphological damages to the prostate tissue and infiltration of inflammatory cells in the model rats, but no obvious changes in the normal controls. At 15 days of treatment, the rats in the PPP + CXC group showed enlarged prostate glandular cavity, mild proliferation of epithelial cells, no obvious infiltration of inflammatory cells in the interstitial tissue, and a few visible fibrous tissues under the light microscope.

CONCLUSIONCompound Xuanju Capsule is efficacious on autoimmune prostatis in rats by reducing inflammatory changes in the prostate tissue and improving the expression of inflammatory factors.

Animals ; Autoimmune Diseases ; blood ; chemically induced ; drug therapy ; Capsules ; Interleukin-10 ; blood ; Interleukin-8 ; blood ; Male ; Prostatic Hyperplasia ; pathology ; Prostatic Secretory Proteins ; Prostatitis ; blood ; chemically induced ; drug therapy ; Random Allocation ; Rats ; Rats, Wistar ; Tumor Necrosis Factor-alpha ; blood