Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma.

Background: Osteosarcoma is the most common malignant primary bone tumor. The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy. Moreover, current treatment regimens bear a significant risk of serious side effects. Thus, there is an unmet clinical need for effective therapies with improved safety profiles. Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines. Methods: In this study, we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma. K7M2 murine osteosarcoma cells were injected, both intramuscular and intraperitoneal, into 60 BALB/c mice on day zero. Animals were then randomized to receive treatment with taurolidine 2% (800 mg/kg), taurolidine 1% (400 mg/kg), or NaCl 0.9% control for seven days by intravenous or intraperitoneal administration. Results: After 35 days, mice were euthanized, and the tumors were harvested for analysis. Eighteen mice were excluded from the analysis due to complications. Body weight was significantly lower in the 2% taurolidine intraperitoneal treatment group from day 9 to 21, consistent with elevated mortality in this group. Intraperitoneal tumor weight was significantly lower in the 1% (p = 0.003) and 2% (p = 0.006) intraperitoneal taurolidine treatment groups compared to the control. No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine. There were no significant differences in microvessel density or mitotic rate between treatment groups. Reduced body weight and elevated mortality in the 2% taurolidine intraperitoneal group suggest that the lower 1% dose is preferable. Conclusions: In conclusion, there is no evidence of antiangiogenic activity, and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited. Moreover, its toxic profile grants further evaluation. Given these observations, further research is necessary to refine the use of taurolidine in osteosarcoma treatment.

Discovery of novel 6-p-tolyl-3-(3,4,5-trimethoxybenzyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine derivative as a potent tubulin inhibitor with promising in vivo antitumor activity.

Building on our prior research, a novel series of trimethoxyphenoxymethyl- and trimethoxybenzyl-substituted triazolothiadiazine compounds has been designed and achieved successfully via a direct ring-closing strategy. Initial biological evaluation illustrated that the most active derivative B5 exhibited significant cell growth inhibitory activity toward HeLa, HT-29, and A549 giving the IC50 values of 0.046, 0.57, and 0.96 µM, respectively, which are greater or similar with CA-4. The mechanism study revealed that B5 caused the G2/M phase arrest, induced cell apoptosis in HeLa cells in a concentration-dependent manner, and also showed potent tubulin polymerization inhibitory effect. Meanwhile, B5 exerted significant antivascular activity in the wound-healing and tube formation assays. Most importantly, B5 remarkably inhibited tumor growth without obvious signs of toxicity in A549-xenograft mice model. These observations indicate that 6-p-tolyl-3-(3,4,5-trimethoxybenzyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine might be considered as the potential lead compound to develop highly efficient anticancer agents with potent selectivity over normal human cells.

The efficacy of taurolidine containing lock solutions for the prevention of central-venous-catheter-related bloodstream infections: a systematic review and meta-analysis.

The incidence of central venous catheter (CVC)-related bloodstream infections is high in patients requiring a long-term CVC. Therefore, infection prevention is of the utmost importance. The aim of this study was to provide an updated overview of randomized controlled trials (RCTs) comparing the efficacy of taurolidine containing lock solutions (TL) to other lock solutions for the prevention of CVC-related bloodstream infections in all patient populations. On 15th February 2021, PubMed, Embase and The Cochrane Library were searched for RCTs comparing the efficacy of TLs for the prevention of CVC-related bloodstream infections with other lock solutions. Exclusion criteria were non-RCTs, studies describing <10 patients and studies using TLs as treatment. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. A random effects model was used to pool individual study incidence rate ratios (IRRs). Subgroup analyses were performed based on the following factors: CVC indication, comparator lock and bacterial isolates cultured. A total of 14 articles were included in the qualitative synthesis describing 1219 haemodialysis, total parenteral nutrition and oncology patients. The pooled IRR estimated for all patient groups together (nine studies; 918 patients) was 0.30 (95% confidence interval 0.19-0.46), favouring the TLs. Adverse events (10 studies; 867 patients) were mild and scarce. The quality of the evidence was limited due to a high risk of bias and indirectness of evidence. The use of TLs might be promising for the prevention of CVC-related bloodstream infections. Large-scale RCTs are needed to draw firm conclusions on the efficacy of TLs.

Synthesis and evaluation of multi-target-directed ligands with BACE-1 inhibitory and Nrf2 agonist activities as potential agents against Alzheimer's disease.

Cumulative evidence suggests that ß-amyloid and oxidative stress are closely related with each other and play key roles in the process of Alzheimer's disease (AD). Multitarget regulation of both pathways might represent a promising therapeutic strategy. Here, a series of selenium-containing compounds based on ebselen and verubecestat were designed and synthesized. Biological evaluation showed that 13f exhibited good BACE-1 inhibitory activity (IC50 = 1.06 µΜ) and potent GPx-like activity (ν0 = 183.0 µM min-1). Aß production experiment indicated that 13f could reduce the secretion of Aß1-40 in HEK APPswe 293T cells. Moreover, 13f exerted a cytoprotective effect against the H2O2 or 6-OHDA caused cell damage via alleviation of intracellular ROS, mitochondrial dysfunction, Ca2+ overload and cell apoptosis. The mechanism studies indicated that 13f exhibited cytoprotective effect by activating the Keap1-Nrf2-ARE pathway and stimulating downstream anti-oxidant protein including HO-1, NQO1, TrxR1, GCLC, and GCLM. In addition, 13f significantly reduced the production of NO and IL-6 induced by LPS in BV2 cells, which confirmed its anti-inflammatory activity as a Nrf2 activator. The BBB permeation assay predicted that 13f was able to cross the BBB. In summary, 13f might be a promising multi-target-directed ligand for the treatment of AD.

Taurolidina para prevenir infecciones asociadas a catéter venoso central en niños con insuficiencia intestinal: experiencia preliminar en un hospital terciario chileno / Taurolidine for the prevention of catheter-related infections in children with intestinal insufficiency: preliminary experience in a Chilean tertiary hospital

INTRODUCCIÓN: Taurolidina es una molécula con propiedades anti-endotóxicas, antimicrobianas y anti-inflamatorias, que inhibe la adhesión bacteriana, lo que ha permitido usarla como terapia de sellado en catéter venoso central de larga duración (CVC) para prevenir infecciones del torrente sanguíneo asociadas a CVC (ITS-CVC). OBJETIVO: Dar a conocer una experiencia preliminar, la primera en Chile, con taurolidina como terapia de sellado para prevenir ITS-CVC y reportar su eficacia. MÉTODO: Se instiló una solución en base a taurolidina en el CVC de tres niños con insuficiencia intestinal, dependientes de alimentación parenteral, atendidos en un hospital terciario de la Región de Valparaíso, y se comparó la tasa de ITS-CVC antes y después de su uso mediante un análisis retrospectivo. RESULTADOS: en los dos pacientes que iniciaron terapia de sellado inmediatamente después de instalado el CVC, la tasa de ITS-CVC se logró llevar a cero, mientras que, en el tercero, portador de un CVC instalado 9 meses antes, con ITS-CVC recurrentes, un nuevo episodio de ITS-CVC obligó a suspender la profilaxis. CONCLUSIONES: La terapia de sellado con solución en base a taurolidina previno las ITS-CVC cuando ésta se inició al momento de instalarse el CVC, no así en un CVC antiguo con ITS-CVC recurrentes.

BACKGROUND: Taurolidine is a molecule with anti-endotoxic, anti-microbial and anti-inflammatory properties that inhibits bacterial adhesion, allowing for its use as lock therapy for the prevention of catheter-related bloodstream infections (CRBSI) in long-term central venous catheters (CVC). AIM: To report a preliminary experience, the first one in Chile, using lock therapy with taurolidine for the prevention of CRBSI and to report its efficacy. METHOD: A taurolidine-based solution was instilled in the CVC of three children with intestinal insufficiency dependent on parenteral nutrition, attended in a Chilean tertiary hospital, and the rate of CRBSI before and after its use was compared in retrospect. RESULTS: In the two patients who started lock therapy immediately after the installation of their CVC, the rate of CRBSI was brought to zero, whereas in the third patient, who had a 9 months-old CVC with a recurrent CRBSI history, an intercurrent CRBSI forced discontinuation of the prophylaxis. CONCLUSIONS: Lock therapy with a taurolidine-based solution prevented CRBSIs when it was begun immediately after installing the CVC, in contrast with an old CVC with a history of recurrent CRBSIs.

Development of triazolothiadiazine derivatives as highly potent tubulin polymerization inhibitors: Structure-activity relationship, in vitro and in vivo study.

Based on our prior work, we reported the design, synthesis, and biological evaluation of fifty-two new triazolothiadiazine-based analogues of CA-4 and their preliminary structure-activity relationship. Among synthesized compounds, Iab was found to be the most potent derivative possessing IC50 values ranging from single-to double-digit nanomolar in vitro, and also exhibited excellent selectivity over the normal human embryonic kidney HEK-293 cells (IC50 > 100 µM). Further mechanistic studies revealed that Iab significantly blocked tubulin polymerization and disrupted the intracellular microtubule network of A549 cells. Moreover, Iab induced G2/M cell cycle arrest by regulation of p-cdc2 and cyclin B1 expressions, and caused cell apoptosis through up-regulating cleaved PARP and cleaved caspase-3 expressions, and down-regulating of Bcl-2. Importantly, in vivo, Iab effectively suppressed tumor growth of A549 lung cancers in a xenograft mouse model without obvious signs of toxicity, confirming its potential as a promising candidate for cancer treatment.

A Novel Selective 11ß-HSD1 Inhibitor, (E)-4-(2-(6-(2,6-Dichloro-4-(Trifluoromethyl)Phenyl)-4-Methyl-1,1-Dioxido-1,2,6-Thiadiazinan-2-yl)Acetamido)Adamantan-1-Carboxamide (KR-67607), Prevents BAC-Induced Dry Eye Syndrome.

Dry eye syndrome is the most common eye disease and it is caused by various reasons. As the balance of the tear film that protects the eyes is broken due to various causes, it becomes impossible to properly protect the eyes. In this study, the protective effects and underlying mechanisms of topical (E)-4-(2-(6-(2,6-dichloro-4-(trifluoromethyl)phenyl)-4-methyl-1,1-dioxido-1,2,6-thiadiazinan-2-yl)acetamido)adamantan-1-carboxamide (KR-67607), a novel selective 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) inhibitor, were investigated in benzalkonium chloride (BAC)-induced dry eye syndrome. BAC-treated rat eyes induced significant increases in ocular surface damage, decreased corneal thickness, corneal basement membrane destruction in the conjunctival epithelium, and expression of pro-inflammatory cytokines tumor necrosis factor-α and 11ß-HSD1. These effects of BAC were reversed by topical KR-67607 treatment. Furthermore, KR-67607 decreased 4-hydroxynonenal expression and increased antioxidant and mucus secretion in BAC-treated rat eyes. Taken together, a novel selective 11ß-HSD1 inhibitor can prevent BAC-induced dry eye syndrome by inhibiting pro-inflammatory cytokine and reactive oxygen species expression via the inhibition of both 11ß-HSD1 activity and expression.

Clinical and economic impact of the taurolidine lock on home parenteral nutrition.

INTRODUCTION: catheter-related bloodstream infections (CRBSI) are one of the most serious concerns in patients on home parenteral nutrition (HPN) which involve high morbidity and cost for the healthcare system. In the last years, taurolidine lock has proven to be beneficial in the prevention of CRBSI; however, the evidence of its efficiency is limited. OBJECTIVE: to determine if taurolidine lock is a cost-effective intervention in patients on HPN. MATERIALS AND METHODS: retrospective study in patients on HPN with taurolidine lock. We compared the CRBSI rate and cost of its complications before and during taurolidine lock. RESULTS: thirteen patients, six (46%) males and seven (54%) females, with a mean age of 61.08 (SD = 14.18) years received taurolidine lock. The total days of catheterization pre and per-taurolidine were 12,186 and 5,293, respectively. The underlying disease was benign in five patients (38.5%) and malignant in eight (61.5%). The CRBSI rate pre vs per-taurolidine was 3.12 vs 0.76 episodes per 1,000 catheter days (p = 0.0058). When the indication was a high CRBSI rate, this was 9.72 vs 0.39 (p < 0.001) in pre and per-taurolidine period respectively. No differences have been observed in the occlusion rates. None of the patients reported any adverse effects. The total cost of CRBSI in the pre-taurolidine period was 151,264.14 euros vs 24,331.19 euros in the per-taurolidine period. CONCLUSIONS: our study shows that taurolidine lock is a cost-effective intervention in patients on HPN with high risk of CRBSI.

ETA as a novel Kv2.1 inhibitor ameliorates ß-cell dysfunction and hyperglycaemia.

The Kv2.1 channel plays an important role in the regulation against pancreatic ß-cell dysfunctions. Therefore, it is regarded as a promising target for drug discovery against type 2 diabetes. In the present study, we found that the small molecule 4-ethoxy-N-{[6-(2-thienyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl]methyl}aniline (ETA), a novel Kv2.1 inhibitor, may be capable of promoting glucose-stimulated insulin secretion and protecting from apoptosis in pancreatic INS-832/13 cells. The assay of ETA on type 2 diabetic mice induced by high-fat diet (HFD)/streptozocin (STZ) confirmed its potency in ameliorating glucose homeostasis. ETA administration reduced fasting blood glucose and glycated haemoglobin levels, improved oral glucose tolerance, and increased serum insulin levels in HFD/STZ mice. Mechanism study demonstrated that ETA protected INS-832/13 cells involving the regulation against protein kinase B and extracellular-regulated protein kinase 1/2 signalling pathways. Our study has confirmed the underlying regulation of Kv2.1 against ß-cell function and also addressed the potential of ETA as a lead compound in the treatment of type 2 diabetes mellitus.

Use of taurolidine in lung transplantation for cystic fibrosis and impact on bacterial colonization.

OBJECTIVES: The presence of bacterial colonization that causes chronic pulmonary infections in cystic fibrosis (CF) patients remains a key issue before lung transplantation. We sought to assess the impact of intraoperative taurolidine lavage on bacterial colonization and long-term outcomes following lung transplantation in CF patients. METHODS: Between 2007 and 2013, 114 CF patients underwent lung transplantation at our institute, and taurolidine 2% bronchial lavage was applied in a substantial proportion of patients (n = 42). A detailed analysis of donor and recipient bacterial colonization status in treatment and control groups and their impact on outcome was performed. RESULTS: The proportion of recipients colonized with Pseudomonas aeruginosa was lower in the taurolidine group at 3 months (P < 0.001) and at 1 year (P = 0.053) postoperatively, despite no differences before transplant (P = 1.000). Moreover, a complete eradication of Burkholderia cepacia and Stenotrophomonas maltophilias colonizations could be achieved in the taurolidine group, whereas in the non-taurolidine group, persistent B. cepacia and S. maltophilias colonizations were observed. Early outcome in the taurolidine group was superior regarding fraction of expired volume in 1 s at 3 and 6 months after surgery with 74.5 ± 14.6 vs 60.4 ± 17.5 (P < 0.001) and 80.6 ± 16.9 vs 67.2 ± 19.4 (P = 0.005) percent of predicted values, respectively. In terms of long-term overall survival (P = 0.277) and freedom from bronchiolitis obliterans syndrome (P = 0.979), both groups were comparable. CONCLUSIONS: Taurolidine might be associated with a reduced proportion of CF patients colonized with multiresistant pathogens, particularly with P. aeruginosa. Long-term results should be further assessed in larger multicentre trials.

Separate and synergistic effects of taurolidine and icodextrin in intra-abdominal adhesion prevention.

BACKGROUND: In our present study, we aimed to evaluate the effects of taurolidine, a blocking agent of fibrin deposition, and icodextrin, a colloid osmotic material that also inhibits fibrin accumulation, and the effect of their application separately and concomittantly in intra-abdominal adhesion prevention. METHODS: Forty BALB/c male mice, weighing 30-35 g and 11-12 weeks old were divided into four groups as follows: group 1: control group, group 2: taurolidine group, group 3: icodextrin group, and group 4: taurolidine and icodextrin group. Animals were sacrificed by cervical dislocation after 14 days. The adhesions were classified and scored by two blinded researchers according to Nair's macroscopic adhesion staging system and microscopically evaluated using Zuhlke classification system. RESULTS: In group 2 there was no mice with score 4. In group 3, scores 3 and 4 were absent. Scores 2, 3, and 4 were not detected in group 4. The mean value of adhesion scores decreased from groups 1 to 4. There was a significant statistical difference between all the groups and group 1. There was no change between the study groups on macroscopic examination, whereas histopathological examination revealed statistically significance between group 4 and other groups. CONCLUSION: Taurolidine and icodextrin, when used alone or together, decrease postoperative intra-abdominal adhesion formation. Macroscopic appearence was not supportive of statistical difference between group 4 and other groups. Microscopic evaluation paves the road for future studies for determining significance when taurolidine and icodextrin are applied concomittantly. Additional experimental studies are required for dose adjustment.

TDAG8 activation attenuates cerebral ischaemia-reperfusion injury via Akt signalling in rats.

BACKGROUND: T-cell death-associated gene 8 (TDAG8), a member of the proton-sensitive G-protein-coupled receptor (GPCR) class with an immune-specific expression profile, was recently shown to be expressed in the rat brain; however, its role in ischaemic stroke remains unknown. METHODS: We initially confirmed the time-dependent expression of TDAG8 in rat brain tissue after ischaemic stroke and reperfusion. Further evaluations were performed to increase TDAG8 expression 6h prior to middle cerebral artery occlusion (MCAO) by injecting a specific agonist, BTB09089, into the lateral ventricle to increase TDAG8 expression. Twenty-four hours before MCAO, a specific small interfering RNA (siRNA) was introduced. The infarction volume, neurological deficit score and cleaved caspase-3 and Bcl-2 expression were used to assess the effects of TDAG8 on ischaemic stroke. Finally, the effects of TDAG8 on the development of primary cortical neurons exposed to oxygen-glucose deprivation (OGD) were investigated. RESULTS: TDAG8 expression increased both in vivo and in vitro. Pretreatment with BTB09089 up-regulated TDAG8 and Bcl-2 expression and down-regulated cleaved caspase-3 expression, while the infarction volume was reduced, and neurological deficits were ameliorated 24 and 72h after MCAO. However, the protective effects of TDAG8 were reversed when its level was reduced in TDAG8-deficient rats. More importantly, these findings are consistent with data from neurons subjected to OGD. CONCLUSIONS: TDAG8 plays an important neuroprotective role through inhibition of neuronal apoptosis and alleviation of neurological deficits by activating the Akt signalling pathway in rats.

Redox-directed cancer therapeutics: Taurolidine and Piperlongumine as broadly effective antineoplastic agents (review).

Targeting the oxygen stress response pathway is considered a promising strategy to exert antineoplastic activity in a broad spectrum of tumor types. Supporting this view, we summarize the mechanism of action of Taurolidine and Piperlongumine, two antineoplastic agents with strikingly broad tumor selectivity. Taurolidine enhances the oxidative stress (ROS) selectively in tumor cells. Its cytotoxicity for various tumor cells in vitro and in vivo, which includes tumor stem cells, is based on the induction of programmed cell death, largely via apoptosis but also necroptosis and autophagy. The redox-directed mechanism of action of Taurolidine is apparent from the finding that reducing agents e.g., N-acetylcysteine or glutathione impair its cytotoxicity, while its effectiveness is enhanced by agents which inhibit the cellular anti­oxidant capacity. A similar redox-directed antineoplastic action is shown by Piperlongumine, a recently described experimental drug of plant origin. Taurolidine is particularly advantageous in surgical oncology as this taurine-derivative can be applied perioperatively or systemically with good tolerability as shown in initial clinical applications.

Tunneled catheters with taurolidine-citrate-heparin lock solution significantly improve the inflammatory profile of hemodialysis patients.

Mortality and morbidity are significantly higher among patients with dialysis catheters, which has been associated with chronic activation of the immune system. We hypothesized that bacteria colonizing the catheter lumen trigger an inflammatory response. We aimed to evaluate the inflammatory profile of hemodialysis patients before and after locking catheters with an antimicrobial lock solution. High-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), IL-10, and tumor necrosis factor alpha (TNF-α) were measured in serum, and levels of mRNA gene expression of IL-6, IL-10, and TNF-α were analyzed in peripheral blood mononuclear cells (PBMC). Samples were obtained at baseline and again after 3 months' use of taurolidine-citrate-heparin lock solution (TCHLS) in 31 hemodialysis patients. The rate of catheter-related bloodstream infections (CRBSI) was 1.08 per 1,000 catheter-days in the heparin period and 0.04 in the TCHLS period (P = 0.023). Compared with the baseline data, serum levels of hs-CRP and IL-6 showed median percent reductions of 18.1% and 25.2%, respectively (P < 0.01), without significant changes in TNF-α or IL-10 levels. Regarding cytokine gene expression in PBMC, the median mRNA expression levels of TNF-α and IL-6 decreased by 20% (P < 0.05) and 19.7% (P = 0.01), respectively, without changes in IL-10 expression levels. The use of TCHLS to maintain the catheter lumen sterility significantly reduces the incidence of CRBSI and improves the inflammatory profile in hemodialysis patients with tunneled catheters. Further studies are needed to evaluate the potential beneficial effects on clinical outcomes.

Complications of total implantable access ports and efficacy of Taurolidine-citrate lock solution against catheter-related infections.

BACKGROUND: Totally, implantable access ports (TIAPs) are used for long standing venous catheterization. This study was designed to present our experiences of the TIAPs applications and efficacy of Taurolidine-citrate lock solution (TCLS) against catheter-related infections. MATERIALS AND METHODS: We evaluated records of the 108 patients implanted with 112 TIAPs, which had been performed using heparin solution or TCLS between 2005 and 2013. RESULTS: Duration of exposure to TIAPs was 17-2051 days (median: 411 days). The primary diagnoses were solid tumours (n = 57), lymphoma (n = 23), haematologic diseases (n = 23), nephrotic syndrome (n = 4), Hirschsprung disease (n = 1). The right external jugular vein was most frequently used vascular access route (72.3%). Mechanical complications were observed in four cases. TIAPs were removed due to remission in 19 cases and infection in 19 cases. Median time from implantation and to the development of infection was 60 days. Heparin solution had been used for care in 33 ports, whereas heparin and TCLS had been used in 79 ports. Based on statistical comparison, use of TCLS was considered to be an important factor for preventing infection (P = 0.03). CONCLUSION: We consider that TCLS reduces infection prevalence so TIAPs would be used more extensively and effectively to prevent infections.

The effects of taurolidine alone and in combination with doxorubicin or carboplatin in canine osteosarcoma in vitro.

BACKGROUND: Osteosarcoma (OS) affects over 8000 dogs/year in the United States. The disease usually arises in the appendicular skeleton and metastasizes to the lung. Dogs with localized appendicular disease benefit from limb amputation and chemotherapy but most die within 6-12 months despite these treatments. Taurolidine, a derivative of taurine, has anti-tumor and anti-angiogenic effects against a variety of cancers. The following in vitro studies tested taurolidine as a candidate for adjuvant therapy for canine OS. Tests for p53 protein status and caspase activity were used to elucidate mechanisms of taurolidine-induced cell death. RESULTS: Taurolidine was cytotoxic to osteosarcoma cells and increased the toxicity of doxorubicin and carboplatin in vitro. Apoptosis was greatly induced in cells exposed to 125 µM taurolidine and less so in cells exposed to 250 µM taurolidine. Taurolidine cytotoxicity appeared caspase-dependent in one cell line; with apparent mutant p53 protein. This cell line was the most sensitive to single agent taurolidine treatment and had a taurolidine-dependent reduction in accumulated p53 protein suggesting taurolidine's effects may depend on the functional status of p53 in canine OS. CONCLUSION: Taurolidine's cytotoxic effect appears dependent on cell specific factors which may be explained, in part, by the functional status of p53. Taurolidine initiates apoptosis in canine OS cells and this occurs to a greater extent at lower concentrations. Mechanisms of cell death induced by higher concentrations were not elucidated here. Taurolidine combined with doxorubicin or carboplatin can increase the toxicity of these chemotherapy drugs and warrants further investigation in dogs with osteosarcoma.

Innate immune responses to Stenotrophomonas maltophilia in immunocompromised pediatric patients and the effect of taurolidine.

BACKGROUND: Stenotrophomonas maltophilia is an emerging pathogen causing invasive infections in immunocompromised pediatric patients, including neonates and pediatric oncology patients. Information on innate immune responses to S. maltophilia and its potential modulation are scarce. METHODS: We established an in vitro S. maltophilia whole blood sepsis model and studied the proinflammatory cytokine production of CD14-positive cells by flow cytometry. We compared the cytokine expression of term newborns (n = 13) and healthy adults (n = 10) and investigated in vitro responses of pediatric oncology patients after recovery from neutropenia (n = 10) with healthy adults (n = 10). We further evaluated the immunomodulatory role of the amino-acid derivative taurolidine in our in vitro sepsis model. RESULTS: Proinflammatory cytokine responses to S. maltophilia were largely diminished in the neonatal population. No remarkable differences were noted for cytokine responses between pediatric oncology patients and healthy controls. Taurolidine inhibited immunoglobulin (IL)-6, IL-8 and tumor necrosis factor-alpha expression in a dose dependent-fashion in both, pediatric oncology patients and healthy controls. CONCLUSION: Deficient immune responses to S. maltophilia require optimized prevention strategies against infection in immunocompromised patients, including neonates. Taurolidine may be an effective immunomodulatory agent in a clinical setting.

Scolicidal activity of taurolidine for the treatment of hydatid disease.

OBJECTIVES: In this experimental study, we have evaluated in vivo and in vitro activities of taurolidine (TRD) against protoscolices of Echinococcus granulosus. BACKGROUND: Scolicidal agent application is mandatory for the interventional treatment of hydatid cysts. Serious adverse effects of current scolicidal agents forced the scientist to search for less toxic chemicals. METHODS: One milliliter of protoscolices suspension was administered into twelve Petri's dishes, six of them containing 5 ml of isotonic saline, and six of them containing 5 ml (5 mg/ml) TRD. Forty, male Balb/c mice were divided into five equal groups. Group 1: protoscolices inoculated group; Group 2: protoscolices inoculated and thereafter immediately administered with a single dose intravenous (IV) 0.5 ml TRD (400 mg/kg); Group 3: protoscolices inoculated and thereafter immediately administered with a single dose intraperitoneal (IP) 0.5 ml TRD (400 mg/kg); Group 4: three months after inoculating the protoscolices, one day before the sacrifice single dose IV 0.5 ml TRD (400 mg/kg) administered; Group 5: three months after inoculating the protoscolices, one day before the sacrifice single dose IP 0.5 ml TRD (400 mg/kg) administered. RESULTS: All the protoscolices were dead in TRD-added Petri's Dishes in 90 minutes. In group 2 and group 3, no mouse had an intraabdominal hydatid cyst. CONCLUSION: The results of this study are encouraging us to suggest TRD as an alternative scolicidal agent. Further clinical studies are needed to define the effectiveness and the mode of application of TRD for the treatment of hydatid disease (Tab. 1, Fig. 4, Ref. 30).

Treatment of long-term catheter-related bloodstream infections with a taurolidine block: a single cancer center experience.

PURPOSE: Catheter-related bloodstream infections (CRBSIs) are a common problem in cancer patients with long-term catheters. The effectiveness of taurolidine, a new antimicrobial solution, in the management of CRBSIs is still unknown. A retrospective analysis of patients with proven CRBSIs treated with a taurolidine block in combination with systemic antibiotic treatment was performed to define its role in the management of CRBSIs. METHODS: Twenty-four episodes of CRBSIs in 23 cancer patients with permanent use of the long-term catheter were treated with a taurolidine block for 3 consecutive days in combination with systemic antibiotic treatment. RESULTS: Treatment was successful in 16 of 24 events (67%). Explantation was performed in 8 cases (33%): in 3 patients due to a second positive blood culture, and in 1 patient due to recurrent fever after the conservative treatment. In 4 patients, the conservative approach was prematurely stopped due to persisting fever. CONCLUSION: Taurolidine-based treatment may be a promising, noninvasive therapeutical approach in the management of long-term catheter-related bloodstream infections in cancer patients.