Disease relevance of Flogovital

• Nimesulide and neonatal renal failure [1].
• Neonatal end-stage renal failure associated with maternal ingestion of cyclo-oxygenase-type-1 selective inhibitor nimesulide as tocolytic [2].
• Nimesulide, thrombocytopenic purpura, and human immunodeficiency virus (HIV) infection [3].
• Indomethacin reduced the extent of atherosclerosis by 55 +/- 4%, whereas nimesulide failed to increase the rate of atherogenesis [4].
• Treatment with L-NAME (NG-mono-methyl-L-arginine ester) or nimesulide shortens the thrombosis time [5].

Psychiatry related information on Flogovital

• Randomized pilot study of nimesulide treatment in Alzheimer's disease [6].
• The causal relationship between nimesulide and liver injury was assessed, using a scoring system elaborated by the French and International consensus meeting group [7].
• In conclusion, the predictive model helps to indicate the risk of ADRs to nimesulide and provides clinicians with an alternative method for decision making when prescribing this drug [8].
• A significant decrease in articular index of joint tenderness (p < 0.05) at 8 weeks and in self assessment of handicap at 4 weeks (p < 0.05), in comparison to baseline, was observed only in patients receiving nimesulide [9].
• Pretreatment with COX-inhibitors rofecoxib (2 mg/kg, i.p.) or nimesulide (2.5 mg/kg, i.p.) displayed significant protection against ethanol-induced withdrawal symptoms, while naproxen (7 mg/kg, i.p.) was not effective in reversing alcohol-induced withdrawal symptoms [10].

High impact information on Flogovital

• Fetal COX-2 inhibition, due to maternal nimesulide assumption, can be responsible for neonatal chronic renal failure [2].
• The long bleeding times in BKB2R(-/-) mice also correct with L-NAME and nimesulide therapy [5].
• The COX-2 inhibitors, NS-398 and nimesulide, significantly suppressed bone metastases with decreased osteoclast number and increased apoptosis in MDA-MB-231 cells [11].
• In vivo, nimesulide increased VEGF production by cancer cells in COX-2-positive and COX-2-negative pancreatic tumors [12].
• CLX and NIME also inhibited cell proliferation, but only in MDR1 cells [13].

Chemical compound and disease context of Flogovital

• Increased expression of cyclooxygenase-2 protein in 4-nitroquinoline-1-oxide-induced rat tongue carcinomas and chemopreventive efficacy of a specific inhibitor, nimesulide [14].
• The chemopreventive potential of a selective cyclooxygenase-2 inhibitor, nimesulide (NIM), against the development of rat superficial urinary bladder carcinomas after initiation with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was examined [15].
• Evaluation of fever, pain, inflammation and nasal obstruction over the 8-day treatment period showed a significant improvement in these parameters for those patients treated with nimesulide when compared with naproxen from day 1, with remission of symptoms starting from day 3 [16].
• In a double-blind study, the efficacy and tolerability of nimesulide (100mg twice daily) were compared with those of diclofenac (50mg twice daily) when administered orally to 50 patients with acute superficial thrombophlebitis of the lower limbs [17].
• It is concluded that nimesulide is as active and safe as paracetamol for the treatment of pyrexia in the elderly [18].

Biological context of Flogovital

• Nimesulide, a preferential cyclooxygenase 2 inhibitor, suppresses peroxisome proliferator-activated receptor induction of cyclooxygenase 2 gene expression in human synovial fibroblasts: evidence for receptor antagonism [19].
• Enhancement of phosphorylation and transcriptional activity of the glucocorticoid receptor in human synovial fibroblasts by nimesulide, a preferential cyclooxygenase 2 inhibitor [20].
• Mutagenesis experiments suggest Ser-530 is also important in time-dependent inhibition by nimesulide and piroxicam [21].
• In contrast, nimesulide had no significant effect on platelet aggregation, although it reduced serum TXB(2) by 29% [22].
• Not only TNF-induced cell death but also apoptosis triggered by the CD95 and TRAIL receptors was enhanced by nimesulide [23].

Anatomical context of Flogovital

• The exposure to lipopolysaccharide (LPS) or epidermal growth factor (EGF) determined an increase of PG and NO production in both cell lines and this increase was strongly reduced by COX-2 inhibitors such as celecoxib (CLX) and nimesulide (NIME) [13].
• We show here that the expression of cyclooxygenase 2 is increased in LNM35 and that a specific cyclooxygenase 2 inhibitor, nimesulide, can inhibit the invasion of LNM35 in vitro through Matrigel containing basement membrane components [24].
• RESULTS: Nimesulide caused significantly less gastric injury using the modified Lanza score (p<0.001) as well as reduced duodenum injury (p=0.039) [22].
• Finally, nimesulide in vitro caused a concentration-dependent net increase in superoxide anion in mitochondria from Sod2(+/-), but not Sod2(+/+) mice [25].
• Furthermore, the nimesulide-treated mutant mice exhibited increased hepatic cytosolic levels of cytochrome c and caspase-3 activity, as well as increased numbers of apoptotic hepatocytes [25].

Associations of Flogovital with other chemical compounds

• By contrast, nimesulide had no effect on both A beta peptides and NF-kappa B. Consistently, mice receiving indomethacin, but no nimesulide, showed a significant reduction in the amyloid burden compared with placebo [26].
• These NSAIDs markedly reduced the levels of the cellular APP holoprotein, further accelerating non-amyloidogenic processes. sAPP alpha release, induced by nimesulide and Thal, was modulated by inhibitors of protein kinase C and Erk mitogen-activated protein (MAP) kinase [27].
• Selective inhibition of COX-2 in humans is associated with less gastrointestinal injury: a comparison of nimesulide and naproxen [22].
• Production of prostaglandin E(2) and prostacyclin by gastric biopsies, also COX-1 dependent, was inhibited by naproxen, but not by nimesulide [22].
• METHODS: Twenty-one patients undergoing PTCA while receiving aspirin 300 mg daily or aspirin plus the selective COX-2 inhibitor nimesulide were compared with 13 patients treated only with fradafiban, a glycoprotein IIb/IIIa antagonist [28].

Gene context of Flogovital

• In COX-2-positive pancreatic cancer, the nimesulide-induced increase of VEGF production by the cancer cells was offset by a decrease in VEGF production by the nonmalignant cell types leading to reduced tumor angiogenesis and growth [12].
• Nimesulide-induced hepatic mitochondrial injury in heterozygous Sod2(+/-) mice [25].
• Our previous study demonstrated that COX-2 selective inhibitor nimesulide decreased aromatase activity from the transcriptional level in breast cancer cells [29].
• Conversely, chronic treatment of the hCOX-2 transgenics with the preferential COX-2 inhibitor nimesulide reversed the hCOX-2-mediated decrease of cortical p18(INK4) mRNA expression in the brain [30].
• Molecular models of the complex between the selective COX-2 inhibitor nimesulide and the cyclooxygenase active site of human prostaglandin-endoperoxide synthase-2 have been built using a combination of homology modelling, conformational searching and automated docking techniques [31].

Analytical, diagnostic and therapeutic context of Flogovital

• CONCLUSIONS: Our data show that nimesulide prevents H. pylori-associated gastric carcinogenesis, and suggest that COX-2 may be a target for chemoprevention of gastric cancer [32].
• Western blotting experiments showed similar expression of COX-2 in both control and nimesulide (250-1500 ppm)-treated mice tumor tissues [33].
• After oral administration of nimesulide 100mg in tablet, granule or suspension to healthy volunteers, the drug was rapidly and extensively absorbed [34].
• Double-blind study of nimesulide in divers with inflammatory disorders of the ear, nose and throat [35].
• Thus factors other than local inhibition of prostaglandins may explain the rapid onset of analgesia that is associated with nimesulide, including a possible central mechanism of pain relief [36].

References