Disease relevance of TAUROLIDINE

• The effects of taurolidine, a novel antineoplastic agent, on human malignant mesothelioma [1].
• Study 2: CD-1 mice were randomized to receive taurolidine (200 mg/kg body weight/i.p.) or saline control [2].
• Taurolidine was not effective in experimental endocarditis [3].
• Nebulised taurolidine and B cepacia bronchiectasis [4].
• In vitro, the antimicrobial agent taurolidine inhibited virtually all of the bacteria tested, including vancomycin-resistant enterococci, oxacillin-resistant staphylococci, and Stenotrophomonas maltophilia, at concentrations between 250 and 2,000 microg/ml [3].

High impact information on TAUROLIDINE

• These studies revealed that a 48-h exposure to taurolidine had little effect on cell cycle distribution in PA-1 and SKOV-3 cells but significantly increased the appearance of DNA debris in the sub-G(0)/G(1) region, an effect consistent with an induction of apoptosis [5].
• A 3-day exposure to Taurolidine inhibited the growth of all of the cell lines evaluated with IC(50)s ranging from 9.6-34.2 microM [5].
• Additional studies assessed phosphotidylserine externalization after a 24-h exposure to taurolidine using annexin-V binding as a cell surface marker [5].
• Bis-(1,1-dioxoperhydro-1,2,4-thiadiazinyl-4)methane (taurolidine) is a synthetic broad-spectrum antibiotic that reacts with bacterial cell membrane components to prevent adhesion to epithelial cell surfaces [5].
• In contrast, in NIH-3T3 cells, taurolidine exposure did not increase DNA debris in the sub-G(0)/G(1) region [5].

Chemical compound and disease context of TAUROLIDINE

• CONCLUSIONS: Taurolidine and taurolidine with heparin significantly inhibit intraperitoneal tumor growth, with different gases used for pneumoperitoneum [6].
• A case is described in which bis (1, 1 dioxoperhydro-1, 2, 4-thiadiazinyl-4-) methane (Taurolin) has saferly been administered on a long term basis to prevent recurrent sepsis in a patient receiving parenteral nutrition [7].
• Animals were randomized into three groups: Control, with measurements taken at baseline and half hourly up to 90 min; Endotoxin, receiving 5microg/Kg E. coli endotoxin intravenously after baseline measurements; and Endotoxin + Taurolidine, receiving 5g of taurolidine via intraperitoneal infusion 1 h before endotoxin administration [8].
• Port site metastases were found in 36.8% after saline, in 37.5% after octreotide and in 0% after taurolidine irrigation (P < 0.05) [9].
• Staphylococcus epidermidis was the most common microorganism isolated before therapy, and the number of its colonies was significantly reduced in taurolidine-treated (p < 0.001) and gentamicin-treated (p < 0.01) subjects [10].

Biological context of TAUROLIDINE

• CONCLUSIONS: Taurolidine has significant antineoplastic activity against MM in vitro and in vivo, in part, due to tumor cell apoptosis [1].
• RESULTS: A 72-h exposure of MM cells to taurolidine showed IC50 of 28-42.7 microm and 50% viability at 49.8-135 microm [1].
• EXPERIMENTAL DESIGN: Cell growth inhibition and viability assays were performed on REN, LRK, and H28 cell lines after 24-72-h exposure to 0-200 microm taurolidine [1].
• O2-, TNF-alpha, CD11b expression, and phagocytosis were significantly increased in the taurolidine group [2].
• The aim of this study was to investigate the immunological effects of taurolidine and correlate findings with survival after a septic challenge in a murine model [2].

Anatomical context of TAUROLIDINE

• Parallel studies revealed that exposure to taurolidine also resulted in poly(ADP-ribose) polymerase cleavage in both ovarian tumor cell lines but not in NIH-3T3 cells [5].
• In this study we have extended this observation and assessed the ability of Taurolidine to purge tumor cells from chimeric mixtures of bone marrow (BM) and neoplastic cells [11].
• The changes of leukocyte counts were not affected by taurolidine [12].
• Neuronal and glial brain cells were obtained from rat fetuses at day 15 of gestation and incubated with taurolidine to investigate its effect on normal brain cells [13].
• After randomization in two groups, the cecum suture line and the parietal peritoneal defect were either lavaged with 1 mL of 0.5% taurolidine/10 IU heparin or with equal amounts of 0.9% normal saline solution [14].

Associations of TAUROLIDINE with other chemical compounds

• Study 3: PM luminal diameters were cultured in vitro +/- 0.5 mg/ml taurolidine and PM luminal diameter antimicrobial function assessed (O2-, NO, TNF-alpha, and phagocytosis) [2].
• The effect of the combination of cefuroxime plus tobramycin, and the effect of taurolidine, an endotoxin-binding agent, on TNF production was also tested [15].
• After incubation of the cells with heparin or taurolidine or both substances, cell kinetics were determined [16].
• In vitro activity of taurolidine, chlorophenol-camphor-menthol and chlorhexidine against oral pathogenic microorganisms [17].
• These include application of an antimicrobial ointment (mupirocin or polysporin [Pfizer, New York, NY]) to the catheter exit site or instillation of an antimicrobial solution (gentamicin or taurolidine) into the catheter lumen [18].

Gene context of TAUROLIDINE

• Although no significant difference was detected concerning the beta1-integrin and CD44 expression, a slightly reduced expression level with 26.7% of negative staining in metastases of the taurolidine/heparin group was observed [14].
• Moreover, taurolidine also induced suppression of VEGF production on the protein and messenger RNA level, as shown by an enzyme-linked immunosorbent assay and by reverse transcription-polymerase chain reaction [19].
• Taurolidine also reduced IL-1 and TNF synthesis induced by the Staphylococcus aureus-derived toxic shock syndrome toxin-1 as well as that induced by nontoxic heat-killed Staphylococcus epidermidis organisms.(ABSTRACT TRUNCATED AT 250 WORDS)[20]
• There was a 80 to 90% reduction in total IL-1 and TNF synthesis induced by LPS at concentrations of taurolidine of 40 to 100 micrograms/mL; the vehicle was without effect [20].
• These consist of anti-LPS monoclonal antibodies (mAbs), naturally occurring proteins and their derivatives (e.g., bactericidal/permeability-increasing protein [BPI], Limulus anti-LPS factor [LALF]), and certain antibiotics (polymyxin B, taurolidine) [21].

Analytical, diagnostic and therapeutic context of TAUROLIDINE

• MM cells exposed to 50-150 microm taurolidine for 24-72 h showed terminal deoxynucleotidyl transferase-mediated nick end labeling staining consistent with apoptosis, as well as structural evidence of apoptosis via electron microscopy [1].
• Study 1: CD-1 mice underwent cecal ligation and puncture, were randomized to receive taurolidine (200 mg/kg body weight/i.p.) or saline control, and studied for end point survival [2].
• RESULTS: In trial 1 lavage with taurolin was not superior to that with saline (five of 18 versus eight of 18 animals survived; P = 0.32) [22].
• However, there was no difference in the incidence of postoperative infection between groups, suggesting that taurolidine intraoperative peritoneal lavage confers no clinical benefit over that with saline [23].
• In the in vivo study, local Taurolidine administration resulted in significant decreases in tumor burden (3+/-1 nodules in Group B animals vs. 649+/-101 nodules in Group A animals) [24].

References