Adult ; Femur Head Necrosis ; chemically induced ; drug therapy ; Glucocorticoids ; therapeutic use ; Humans ; Male ; Paraquat ; poisoning

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

OBJECTIVE: To investigate the effects of Tongxinluo (TXL) on thromboangiitis obliterans (TAO) and the underlying mechanisms. METHODS: Ninety male C57/BL6J mice were randomly divided into 6 groups according to a random number table: the sham group, TAO model group, Compound Danshen Tablet (CDT) group, and the high-, medium-, and low-dose TXL groups. All mice except the sham group were injected with sodium laurate (0.1 mL, 5 mg/mL) in the femoral artery to establish TAO mouse model. After modeling, mice in the sham and TAO model groups were intragastrically administered 0.5% (w/v) sodium carboxymethylcellulose, mice in the CDT group were intragastrically administered 0.52 g/kg CDT, and mice in the TXL-H, TXL-M, and TXL-L groups were intragastrically administered 1.5, 0.75, and 0.38 g/kg TXL, respectively. After 4 weeks of gavage, the recovery of blood flow in the lower limbs of mice was detected by Laser Doppler Imaging. The pathological changes and thrombosis of the femoral artery were observed by morphological examination. The expressions of tumor necrosis factor α (TNF-α) and inducible nitric oxide synthase (iNOS) in the femoral artery wall were detected by HE staining. Levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α), endothelin-1 (ET-1), interleukin (IL)-1β and IL-6 were measured using enzyme-linked immunosorbent assay (ELISA). Levels of activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB) were detected by a fully automated biochemical analyzer. RESULTS: TXL promoted the restoration of blood flow in the lower limbs, reduced the area of thrombosis in the femoral artery, and alleviated the pathological changes in the femoral artery wall. Moreover, the levels of TXB2, ET-1, IL-6, IL-1β, TNF-α and iNOS were significantly lower in the TXL groups compared with the model group (P<0.05 or P<0.01), while the level of 6-keto-PGF1α was significantly higher (P<0.01). In addition, APTT, PT, and TT were significantly prolonged in TXL groups compared with the model group (P<0.05 or P<0.01), and FIB levels were significantly decreased compared with the model group (P<0.01). CONCLUSIONS TXL had a protective effect on TAO mice, and the mechanism may involve inhibition of thrombosis and inflammatory responses. TXL may be a potential drug for the treatment of TAO.
Mice ; Male ; Animals ; Thromboangiitis Obliterans/chemically induced* ; Interleukin-6/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Thrombosis

We investigated the pathobiological course of uranyl nitrate (UN) induced polyuric acute tubular necrosis (ATN) in male Sprague Dawley rats. UN (5mg/kg 15mg/kg and 3Omg/kg) in 5% NaHCO3 induced weight loss, polydipsia, and polyuria 24 hrs after injection when compared to the controls which were treated with 5% NaHCO3 only. Twenty four hours following the injection of UN, serum creatinine and blood urea nitrogen levels had increased. These changes continued for at least 72 hours, although the concentration of uranium had decreased. Light microscopic studies conducted 24 hours after injection, revealed partial degeneration and necrosis of the proximal tubules and many casts m the distal convoluted tubules. These changes progressed for 72 hours. Despite this tubular damage, the glomeruli were relatively intact. 5 days after injection, the epithelial cells lining the proximal tubules displayed regenerative activities; these findings were more prominent after 10 days. Through electron microscopic examination, we observed the destruction of mitochondria in the proximal tubular cells, a possible cause of polyuria. Ten days post injection regenerative activities in the proximal tubular cells showed that the maturation of intracellular organelles followed the proliferation of the premature cells.
Animal ; Kidney Failure, Acute/chemically induced* ; Kidney Function Tests ; Kidney Tubular Necrosis, Acute/chemically induced* ; Male ; Rats ; Rats, Inbred Strains ; Uranium/pharmacology* ; Uranyl Nitrate/pharmacology*

Drug-induced nephrotoxicity is very common in both new drug development and clinic practice. Various drugs can induce kidney injuries, including tubulointerstitial, glomerular and renal vascular disease. To investigate the mechanism of drug induced nephrotoxicity is important for risk reduction of new drug development, reasonable drug usage, early discovery and effective prevention/treatment of adverse effects in clinics.
Acute Kidney Injury ; chemically induced ; Animals ; Anti-Infective Agents ; adverse effects ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; Antineoplastic Agents ; adverse effects ; Humans ; Immunosuppressive Agents ; adverse effects ; Kidney Diseases ; chemically induced ; Kidney Tubular Necrosis, Acute ; chemically induced ; Nephritis, Interstitial ; chemically induced ; Renal Insufficiency ; chemically induced

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

Aristolochic Acids ; adverse effects ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Kidney Tubular Necrosis, Acute ; chemically induced ; prevention & control

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

Acute Disease ; Adult ; Female ; Humans ; Male ; Middle Aged ; Organophosphate Poisoning ; Respiratory Insufficiency ; blood ; chemically induced ; Tumor Necrosis Factor-alpha ; metabolism

To investigate the effect of prophylactic aucubin (AU) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. 
 Methods: Male BABL/c mice were randomly divided into a control group, an ALI group, and an AU treatment group, 16 mice in each group. ALI mice were injected with LPS (5 mg/kg, intratracheal injection), and AU (10 mg/kg) was injected intraperitoneally 30 min ahead. After LPS injection for 6 hours mice were sacrificed, the morphological changes of lung tissues were detected by HE staining and the lung injury score was obtained. The mRNA expression of tumor necrosis factor-α (TNF-α) and interleukin 10 (IL-10) in lung tissue was detected by real-time PCR. The total protein and lactate dehydrogenase (LDH) activity, the cell count, and the protein content of TNF-α and IL-10 in the mouse bronchoalveolar lavage fluid (BALF) were detected.
 Results: Compared with ALI mice, the pathological damage score of lung tissue was significantly reduced in the AU group, the total number of BALF cells, neutrophils, and macrophages were significantly decreased, LDH activity and the total protein content were also significantly decreased (all P<0.01). In addition, AU can reduce the mRNA and protein expression of TNF-α in lung of ALI mice, and increase the mRNA and protein expression of IL-10 (all P<0.01).
 Conclusion: AU can reduce LPS-induced ALI in mice.
Acute Lung Injury ; chemically induced ; Animals ; Bronchoalveolar Lavage Fluid ; Iridoid Glucosides ; Lipopolysaccharides ; Lung ; Male ; Mice ; Tumor Necrosis Factor-alpha