Tumor Necrosis Factor is one of the cell factors with much stronger anti-tumor activity. In this study, photoactive arylazide-4-azidobenzoic acid was modified to Tumor Necrosis Factor-alpha (TNF-alpha). The IR data (2127cm(-1)) was given to confirm the modification. By photo-immobilization, this modified TNF-a was immobilized on cell culture polystyrene. Both the relation between the amount of TNF-alpha in feed and immobilized TNF-alpha and the influence of different UV irradiation time on photo-immobilization are discussed. Microscopic observations of the photo-immobilization TNF-alpha were made by use of scanning electrom microscope and atomic force microscope.
Female ; Humans ; Photochemistry ; Tumor Necrosis Factor-alpha ; chemistry ; therapeutic use ; Ultraviolet Rays ; Uterine Cervical Neoplasms ; therapy

Graft vs Host Disease ; drug therapy ; Humans ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors ; therapeutic use

For decades, the gut has been thought to play an important role in sepsis pathogenesis. Sepsis is a serious life-threatening, chronic condition of an infection caused by dysregulated host immune response in most of the intensive care unit patients. Probiotics have dual roles in polymicrobial sepsis i.e. probiotics may induce sepsis in many cases and may prevent its prognosis in many cases. Experimental evidence from both pre-clinical and clinical studies have demonstrated that probiotic therapy ameliorates various inflammatory mediators such as tumor necrosis factor, interleukin-10 (IL-10), IL-6, etc., in septicemia. In addition, probiotic use was also found to reduce the severity of pathological conditions associated with irritable bowel disorder and prevent development of endocarditis in septicemia. On contrary, probiotic therapy in neonatal and athymic adult mice fail to provide any beneficial effects on mortality and sepsis-induced inflammation. Importantly, in few clinical trials probiotic use was found to aggravate sepsis by promoting inflammatory cascade rather than suppressing it. This review discusses various studies regarding the beneficial or harmful effects associated with probiotic therapy in sepsis.
Animals ; Humans ; Inflammation ; Mice ; Probiotics/therapeutic use* ; Sepsis/therapy* ; Tumor Necrosis Factor-alpha

A case of juvenile psoriatic arthritis in a 12 year-old boy was reported. The patient had a history of one and half a year of bilateral heel pain, followed by pain in the right knee and ankle and right hip joint. He developed psoriatic lesions affecting his nails and skin. He had increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) contents. Human leukocyte antigen (HLA) B27 was detected but serum rheumatoid factor was not in the patient. A skin biopsy revealed psoriasis and ultrasonography demonstrated synovitis in right knee and ankle. Juvenile psoriatic arthritis was diagnosed based on his physical, laboratory and skin biopsy findings. A treatment with nonsteroidal anti-inflammatory drugs and sulfasalazine produced no effect. Leflunomide in conjunction with anti-TNF biologic agents (Etanercept) was administered, followed by symptomatic improvement 2 weeks later.
Arthritis, Psoriatic ; diagnosis ; drug therapy ; etiology ; Child ; Diagnosis, Differential ; Etanercept ; Humans ; Immunoglobulin G ; therapeutic use ; Male ; Receptors, Tumor Necrosis Factor ; therapeutic use ; Tumor Necrosis Factor-alpha ; antagonists & inhibitors

Rheumatoid arthritis (RA) is a progressive inflammatory disease with severe symptoms of pain and stiffness. Chronic persistent inflammation of RA often leads to joint destruction, deformity and limitation of function, which ultimately results in significant deterioration of quality of life (QoL). RA is characterized pathogenetically by immunologically driven, chronic synovitis, and production of autoantibodies, such as rheumatoid factor and anti-cyclic citrullinated peptide antibodies. Although the cause of RA is yet unknown, advances in the molecular biology led to in-depth understanding of its pathogenesis, and have fostered the recent development of novel treatments. The last decade has seen the dramatic change in the landscape of RA treatment with more aggressive therapy early in the disease course and with treatment guided by a structured assessment of disease activity, with the ultimate goal of reaching remission. In addition, prevention and control of joint damage and improvement in QoL are important goals. To achieve these goals, a multidisciplinary approach to reduce disease activity with disease modifying antirheumatic drugs and biological therapy is needed. We also need to find ways to identify those patients who are at risk for more rapid disease progression who would benefit from intensive therapy early in the course of disease.
Antibodies, Monoclonal/therapeutic use ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/*diagnosis/etiology/*therapy ; Biological Products/therapeutic use ; Humans ; Tumor Necrosis Factor-alpha/antagonists & inhibitors

OBJECTIVESTo obtain high therapeutic effect and low toxicity single-chain immunotoxin against hepatocellular carcinoma (HCC).

METHODSHuman mutant tumor necrosis factor-alpha (mTNFalpha) was linked with the 3' end of humanized single-chain Fv against HCC (hscFv25) in pGEX4T-1 vector. The anti-HCC immunotoxin was expressed in Escherichia coli and identified by western blot. The primary tumor regression trial in nude mice bearing HCC was evaluated the targeting therapeutic value of hscFv25-mTNFalpha. The tumor tissues were stained by immunohistochemical with TNFalpha antibody.

RESULTSThe expression of single-chain immunotoxin hscFv25-mTNFalpha was 12% of total bacteria proteins. The tumor regression trials of hscFv25-mTNFalpha showed 5/5 effective. It had 2/5 completely remission and 3/5 partly remission. The therapeutic result of hscFv25-mTNFalpha was better than that of mTNFalpha (F=8.70, 0.05). The HCC tissue treated by hscFv25-mTNFalpha expressed TNFalpha positive reaction. The positive granule mainly existed in HCC cytoplasm.

CONCLUSIONThe single-chain immunotoxin hscFv25-mTNFalpha has high therapeutic effect and low toxicity. It has potentialities for clinical application.

Animals ; Immunoglobulin Fragments ; therapeutic use ; Immunohistochemistry ; Immunotoxins ; therapeutic use ; Liver Neoplasms, Experimental ; therapy ; Mice ; Mice, Inbred BALB C ; Tumor Necrosis Factor-alpha ; therapeutic use

Humans ; Arthritis, Psoriatic/drug therapy* ; Interleukin-17 ; Interleukin Inhibitors ; Antirheumatic Agents/therapeutic use* ; Tumor Necrosis Factor-alpha/therapeutic use* ; Interleukin-23/therapeutic use*

OBJECTIVETo evaluate the therapeutic effect of vascular endothelial growth factor (VEGF) and tumor necrosis factor receptor (TNFR) on avascular necrosis of the femoral head in rabbits.

METHODSAvascular necrosis of the femoral head was induced in 26 New Zealand white rabbits by injections of horse serum and prednisolone. The rabbits were then divided into VEGF/TNFR treatment group, VEGF treatment group, and untreated model group, with another 4 normal rabbits as the normal control group. In the two treatment groups, the therapeutic agents were injected percutaneously into the femoral head. Enzyme-linked immunosorbent assay was performed to determine the concentration of TNF-alpha in rabbit serum followed by pathological examination of the changes in the bone tissues, bone marrow hematopoietic tissue and the blood vessels in the femoral head.

RESULTSCompared with the model group, the rabbits with both VEGF and TNFR treatment showed decreased serum concentration of TNF-alpha with obvious new vessel formation, decreased empty bone lacunae in the femoral head and hematopoietic tissue proliferation in the bone marrow cavity.

CONCLUSIONPercutaneous injection of VEGF and TNFR into the femoral head can significantly enhance bone tissue angiogenesis and ameliorate osteonecrosis in rabbits with experimental femoral head necrosis.

Animals ; Drug Therapy, Combination ; Female ; Femur Head Necrosis ; chemically induced ; drug therapy ; Male ; Rabbits ; Random Allocation ; Receptors, Tumor Necrosis Factor ; therapeutic use ; Tumor Necrosis Factor-alpha ; blood ; Vascular Endothelial Growth Factor A ; therapeutic use

OBJECTIVEClinical studies have shown decreased levels of sexual hormones, particularly testosterone deficiency, in men with chronic heart failure (CHF). The authors aimed to investigate the effect of testosterone on cardiac function and the possible mechanism of androgen protecting the heart in male rats.

METHODSForty-three male SD rats were randomly divided into 3 groups: right heart failure (RHF, n = 15), physiologic testosterone treatment (TT, n = 15) and control (n = 13). The RHF group was given intraperitoneal injection of monocrotaline at 60 mg/kg to make RHF models; the TT group was injected with testosterone at 5 mg/kg 3 days after monocrotaline administration; and the control group received equal volume of saline. The CD34+ cells in the peripheral blood of each rat were counted by flow cytometry. The levels of serum testosterone and tumor necrosis factor alpha (TNF-alpha) were measured by chemiluminescence immunoassay and enzyme linked immunosorbent assay, respectively. The hearts, lungs and livers of all the surviving rats were excised at 6 weeks for pathological and immunohistochemical examinations.

RESULTSThe level of serum testosterone was gradually decreased, while that of TNF-alpha obviously increased in the RHF group. After testosterone treatment, the TT group showed a remarkable improvement of cardiac performance and a significant decrease in the level of serum TNF-alpha as compared with the RHF group. Statistically significant differences were observed neither in the CD34+ cell count in the peripheral blood nor in the CD34+ expression of the myocardial cells between the TT and RHF groups.

CONCLUSIONPhysiological supplementation of testosterone can improve the cardiac function of RHF male rats, probably through its inhibition of TNF-alpha rather than by autologous mobilization of bone marrow stem cells.

Animals ; Heart Failure ; drug therapy ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Testosterone ; blood ; therapeutic use ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the protective effect of mannitol therapy on the vital organs and explore the underlying mechanisms in New Zealand rabbits with severe burn injury.

METHODSTwelve New Zealand rabbits with severe burn injury (30% of TBSA) were randomized to receive fluid resuscitation with saline (control) or mannitol therapy starting at 1 h after the injury. Serum and urine samples were collected before and at 1, 4, 8, 24, and 48 h after the injury for detection of TNF-α, IL-6, ALT, AST, GGT, CK, CK-MB, BUN and Cr levels using sandwich ELISA.

RESULTSOne hour after sever burn injury, the serum levels of TNF-&alpha; and IL-6 began to increase along with ALT, AST, GGT, CK, CK-MB, BUN and Cr levels. Compared with control group, the rabbits in mannitol group showed significantly higher 48 h urine excretion of TNF-&alpha; (145 ± 8 vs 78 ± 1 0 pg/ml, P<0.05) and IL-6 (93 ± 6 vs 40 ± 8 pg/ml, P<0.05) but with lowered serum levels of TNF-&alpha; (0.62 ± 0.02 vs 0.83 ± 0.02 pg/ml, P<0.05) and IL-6 (0.45 ± 0.03 vs 0.56 ± 0.03 pg/ml, P<0.05) as well as lowered serum ALT, AST, GGT, CK, CK-MB, BUN and Cr levels (P<0.05).

CONCLUSIONIn rabbits with severe burn injury, mannitol therapy can decrease serum TNF-&alpha; and IL-6 levels early after the injury to ameliorate potential functional impairment of the heart, liver and kidneys.

Animals ; Burns ; blood ; drug therapy ; Fluid Therapy ; Interleukin-6 ; blood ; Male ; Mannitol ; therapeutic use ; Rabbits ; Tumor Necrosis Factor-alpha ; blood