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1.
Oncol Res ; 32(7): 1163-1172, 2024.
Article de Anglais | MEDLINE | ID: mdl-38948019

RÉSUMÉ

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.


Sujet(s)
Tumeurs osseuses , Modèles animaux de maladie humaine , Ostéosarcome , Taurine , Thiadiazines , Charge tumorale , Animaux , Taurine/analogues et dérivés , Taurine/pharmacologie , Taurine/usage thérapeutique , Thiadiazines/pharmacologie , Thiadiazines/usage thérapeutique , Ostéosarcome/traitement médicamenteux , Ostéosarcome/anatomopathologie , Ostéosarcome/vascularisation , Souris , Tumeurs osseuses/traitement médicamenteux , Tumeurs osseuses/anatomopathologie , Charge tumorale/effets des médicaments et des substances chimiques , Densité microvasculaire/effets des médicaments et des substances chimiques , Souris de lignée BALB C , Lignée cellulaire tumorale , Antinéoplasiques/pharmacologie , Antinéoplasiques/usage thérapeutique , Inhibiteurs de l'angiogenèse/pharmacologie , Inhibiteurs de l'angiogenèse/usage thérapeutique , Humains , Néovascularisation pathologique/traitement médicamenteux
2.
Hepatol Commun ; 8(7)2024 Jul 01.
Article de Anglais | MEDLINE | ID: mdl-38967598

RÉSUMÉ

BACKGROUND: Bile acids mediate gut-liver cross-talk through bile acid receptors. Serum, hepatic, and microbial bile acid metabolism was evaluated in HCV-compensated chronic liver disease. METHODS: Patients underwent liver biopsy; portal and peripheral blood were obtained before (HCVi), and 6 months after sustained virologic response (SVR), splenic blood was obtained only after SVR. The fecal microbiome and liver transcriptome were evaluated using RNA-Seq. Twenty-four bile acids were measured in serum, summed as free, taurine-conjugated bile acids (Tau-BAs), and glycine-conjugated bile acids. RESULTS: Compared to SVR, HCVi showed elevated conjugated bile acids, predominantly Tau-BA, compounded in HCVi cirrhosis. In the liver, transcription of bile acids uptake, synthesis, and conjugation was decreased with increased hepatic spillover into systemic circulation in HCVi. There was no difference in the transcription of microbial bile acid metabolizing genes in HCVi. Despite an overall decrease, Tau-BA remained elevated in SVR cirrhosis, mainly in splenic circulation. Only conjugated bile acids, predominantly Tau-BA, correlated with serum proinflammatory markers and hepatic proinflammatory pathways, including NLRP3 and NFKB. Among hepatic bile acid receptors, disease-associated conjugated bile acids showed the strongest association with hepatic spingosine-1-phosphate receptor 2 (S1PR2). CONCLUSIONS: Enhanced expression of hepatic S1PR2 in HCVi and HCVi-cirrhosis and strong associations of S1PR2 with Tau-BAs suggest pathological relevance of Tau-BA-hepatic S1PR2 signaling in chronic liver disease. These findings have therapeutic implications in chronic liver diseases.


Sujet(s)
Acides et sels biliaires , Foie , Récepteurs de la sphingosine-1-phosphate , Taurine , Humains , Acides et sels biliaires/métabolisme , Acides et sels biliaires/sang , Mâle , Taurine/sang , Femelle , Adulte d'âge moyen , Foie/métabolisme , Récepteurs de la sphingosine-1-phosphate/métabolisme , Hépatite C chronique/traitement médicamenteux , Hépatite C chronique/métabolisme , Hépatite C chronique/complications , Cirrhose du foie/métabolisme , Cirrhose du foie/virologie , Microbiome gastro-intestinal , Réponse virologique soutenue , Protéine-3 de la famille des NLR contenant un domaine pyrine/métabolisme , Adulte , Sujet âgé
3.
Reproduction ; 168(2)2024 Aug 01.
Article de Anglais | MEDLINE | ID: mdl-38855990

RÉSUMÉ

In brief: Mammalian spermatozoa actively generate reactive oxygen species (ROS) during capacitation, a maturational process necessary for fertilization in vivo. This study shows that hypotaurine, a precursor of taurine present in the oviduct, is incorporated and concentrated in hamster sperm cells via the taurine transporter, TauT, for cytoprotection against self-produced ROS. Abstract: To achieve fertilization competence, mammalian spermatozoa undergo capacitation, during which they actively generate reactive oxygen species (ROS). Therefore, mammalian spermatozoa must protect themselves from these self-generated ROS. The mammalian oviductal fluid is rich in hypotaurine, a taurine precursor, which reportedly protects mammalian spermatozoa, including those of hamsters, from ROS; however, its precise mechanism remains unknown. This study aimed to elucidate the mechanism underlying hypotaurine-mediated protection of spermatozoa from ROS using hamsters, particularly focusing on the taurine/hypotaurine transporter TauT. The effect of hypotaurine on sperm motility and ROS levels was tested using sperm motility analysis and the CellROX dye and luminol assays. RNA sequencing analysis was performed to verify TauT expression. We found that hypotaurine was necessary for maintaining sperm motility and hyperactivated motility. Hypotaurine did not scavenge extracellular ROS but lowered intracellular ROS levels and was incorporated and concentrated in hamster spermatozoa. TauT was detected at both mRNA and protein levels. ß-Alanine blocked hypotaurine transport, increased intracellular ROS levels, and inhibited hyperactivation. Elimination of Na+ or Cl- ions inhibited hypotaurine transport and increased intracellular ROS levels. Thus, these results indicated that hamster spermatozoa incorporated and concentrated hypotaurine in sperm cells via TauT to protect themselves from self-generated ROS.


Sujet(s)
Espèces réactives de l'oxygène , Capacitation des spermatozoïdes , Mobilité des spermatozoïdes , Spermatozoïdes , Taurine , Animaux , Mâle , Taurine/analogues et dérivés , Taurine/pharmacologie , Spermatozoïdes/métabolisme , Spermatozoïdes/effets des médicaments et des substances chimiques , Espèces réactives de l'oxygène/métabolisme , Cricetinae , Mobilité des spermatozoïdes/effets des médicaments et des substances chimiques , Capacitation des spermatozoïdes/effets des médicaments et des substances chimiques , Protéines de transport membranaire/métabolisme , Protéines de transport membranaire/génétique , Glycoprotéines membranaires/métabolisme , Glycoprotéines membranaires/génétique , Mesocricetus
4.
Antimicrob Agents Chemother ; 68(7): e0038124, 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38864612

RÉSUMÉ

Candida auris is an evolving and concerning global threat. Of particular concern are bloodstream infections related to central venous catheters. We evaluated the activity of taurolidine, a broad-spectrum antimicrobial in catheter lock solutions, against 106 C. auris isolates. Taurolidine was highly active with a MIC50/MIC90 of 512/512 mg/L, over 20-fold lower than lock solution concentrations of ≥13,500 mg/L. Our data demonstrate a theoretical basis for taurolidine-based lock solutions for prevention of C. auris catheter-associated infections.


Sujet(s)
Antifongiques , Candida auris , Infections sur cathéters , Tests de sensibilité microbienne , Taurine , Thiadiazines , Thiadiazines/pharmacologie , Taurine/analogues et dérivés , Taurine/pharmacologie , Infections sur cathéters/microbiologie , Infections sur cathéters/traitement médicamenteux , Infections sur cathéters/prévention et contrôle , Humains , Antifongiques/pharmacologie , Candida auris/effets des médicaments et des substances chimiques , Voies veineuses centrales/microbiologie , Voies veineuses centrales/effets indésirables , Candidose/microbiologie , Candidose/traitement médicamenteux , Candidémie/microbiologie , Candidémie/traitement médicamenteux
5.
PLoS One ; 19(6): e0304522, 2024.
Article de Anglais | MEDLINE | ID: mdl-38837993

RÉSUMÉ

BACKGROUND: A subset of individuals (10-20%) experience post-COVID condition (PCC) subsequent to initial SARS-CoV-2 infection, which lacks effective treatment. PCC carries a substantial global burden associated with negative economic and health impacts. This study aims to evaluate the association between plasma taurine levels with self-reported symptoms and adverse clinical outcomes in patients with PCC. METHODS AND FINDINGS: We analyzed the plasma proteome and metabolome of 117 individuals during their acute COVID-19 hospitalization and at the convalescence phase six-month post infection. Findings were compared with 28 age and sex-matched healthy controls. Plasma taurine levels were negatively associated with PCC symptoms and correlated with markers of inflammation, tryptophan metabolism, and gut dysbiosis. Stratifying patients based on the trajectories of plasma taurine levels during six-month follow-up revealed a significant association with adverse clinical events. Increase in taurine levels during the transition to convalescence were associated with a reduction in adverse events independent of comorbidities and acute COVID-19 severity. In a multivariate analysis, increased plasma taurine level between acute and convalescence phase was associated with marked protection from adverse clinical events with a hazard ratio of 0.13 (95% CI: 0.05-0.35; p<0.001). CONCLUSIONS: Taurine emerges as a promising predictive biomarker and potential therapeutic target in PCC. Taurine supplementation has already demonstrated clinical benefits in various diseases and warrants exploration in large-scale clinical trials for alleviating PCC.


Sujet(s)
COVID-19 , SARS-CoV-2 , Taurine , Humains , Taurine/sang , COVID-19/sang , COVID-19/complications , Femelle , Mâle , Adulte d'âge moyen , SARS-CoV-2/isolement et purification , Adulte , Marqueurs biologiques/sang , Sujet âgé , Syndrome de post-COVID-19 , Études cas-témoins , Métabolome ,
6.
Int J Biol Macromol ; 273(Pt 2): 132762, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38876232

RÉSUMÉ

Wound dressing diligently facilitate healing by fostering hemostasis, immunoregulation, the angiogenesis, and collagen deposition. Our methodology entails fabricating chitosan-taurine nanoparticles (CS-Tau) through an ionic gelation method. The morphology of CS-Tau was observed utilizing Transmission electron microscopy (TEM), scanning electron microscopy (SEM) and Dynamic Light Scattering (DLS). The nanoparticles are subsequently incorporated into carboxymethyl chitosan hydrogels for crosslinking by EDC-NHS, yielding hydrogel dressings (CMCS-CS-Tau) designed to extend the duration of taurine release. In vitro investigations confirmed that these innovative compound dressings displayed superior biodegradation, biocompatibility, cytocompatibility, and non-toxicity, in addition to possessing anti-inflammatory properties, and stimulating the proliferation and mobility of human umbilical vein endothelial cells (HUVECs). Experiments conducted on mice models with full-thickness skin removal demonstrated that CMCS-CS-Tau efficaciously aided in wound healing by spurring angiogenesis, and encouraging collagen deposition. CMCS-CS-Tau can also minimize inflammation and promote collagen deposition in chronic diabetic wound. Hence, CMCS-CS-Tau promotes both acute and chronic diabetic wound healing. Furthermore, the sustained release mechanism of CMCS-CS-Tau on taurine reveals promising potential for extending its clinical utility in relation to various biological effects of taurine.


Sujet(s)
Chitosane , Cellules endothéliales de la veine ombilicale humaine , Hydrogels , Nanoparticules , Taurine , Cicatrisation de plaie , Chitosane/composition chimique , Chitosane/analogues et dérivés , Chitosane/pharmacologie , Cicatrisation de plaie/effets des médicaments et des substances chimiques , Animaux , Nanoparticules/composition chimique , Humains , Souris , Hydrogels/composition chimique , Hydrogels/pharmacologie , Taurine/analogues et dérivés , Taurine/composition chimique , Taurine/pharmacologie , Cellules endothéliales de la veine ombilicale humaine/effets des médicaments et des substances chimiques , Diabète expérimental/traitement médicamenteux , Prolifération cellulaire/effets des médicaments et des substances chimiques , Mâle , Réactifs réticulants/composition chimique
7.
Addict Sci Clin Pract ; 19(1): 49, 2024 06 13.
Article de Anglais | MEDLINE | ID: mdl-38872214

RÉSUMÉ

BACKGROUND: The 15-method is a targeted screening and treatment approach for alcohol problems in primary care. The 15-method used in primary care has proven as effective as specialized treatment for mild to moderate alcohol dependence in Sweden. A feasibility study of the 15-method in Danish primary care found the method acceptable and feasible. AIMS: To evaluate the effectiveness of the 15-method in a Danish primary care setting in (1) lowering the proportion of patients exceeding the Danish low-risk alcohol consumption limit of ten standard units per week and a maximum of four standard units on a single day for men and women, and (2) increasing the likelihood of alcohol use being addressed during a consultation in general practice. Further, the rate of prescribed pharmacological treatment for alcohol problems (Disulfiram, Naltrexone, Acamprosate, and Nalmefene) will be measured along with the use of the biomarkers Alanine Transaminase and Gamma-Glutamyl Transferase. METHODS: Stepped wedge cluster randomized controlled trial in sixteen general practices in the Region of Southern Denmark. Following a three-month baseline, the practices are randomly assigned to launch dates in one of four clusters. General practitioners and nurses receive three hours of training in the 15-method before launch. Patient questionnaires will collect data on alcohol consumption levels among patients affiliated with the practices. The healthcare professionals will register consultations in which alcohol is addressed in their patient filing system. Pharmacological treatment rates and the use of biomarkers will be collected through Danish national registries. The study follows the Medical Research Council's guidelines for developing and evaluating complex interventions. DISCUSSION: From the patient's perspective, the 15-method may help identify alcohol-related problems at an earlier stage with flexible treatment offers in a familiar setting. For healthcare professionals, it addresses a traditionally challenging topic by equipping them with concrete tools, communication training, and clear treatment directives. From a societal perspective, primary care holds a unique position to identify hazardous and harmful alcohol use across different age groups, with potential public health and economic benefits through early identification and intervention. TRIAL REGISTRATION: Clinicaltrials.gov NCT05916027. Retrospectively registered 22 June 2023.


Sujet(s)
Substances à effet antabuse , Alcoolisme , Disulfirame , Naltrexone , Soins de santé primaires , Humains , Soins de santé primaires/organisation et administration , Danemark , Naltrexone/usage thérapeutique , Naltrexone/analogues et dérivés , Alcoolisme/diagnostic , Alcoolisme/traitement médicamenteux , Alcoolisme/thérapie , Mâle , Femelle , Substances à effet antabuse/usage thérapeutique , Disulfirame/usage thérapeutique , Acamprosate/usage thérapeutique , Adulte , Taurine/analogues et dérivés , Taurine/usage thérapeutique , Alanine transaminase/sang , gamma-Glutamyltransferase/sang , Adulte d'âge moyen , Dépistage de masse/méthodes , Essais contrôlés randomisés comme sujet
8.
PLoS One ; 19(6): e0305853, 2024.
Article de Anglais | MEDLINE | ID: mdl-38913632

RÉSUMÉ

The intricate process of neuronal differentiation integrates multiple signals to induce transcriptional, morphological, and electrophysiological changes that reshape the properties of neural precursor cells during their maturation and migration process. An increasing number of neurotransmitters and biomolecules have been identified as molecular signals that trigger and guide this process. In this sense, taurine, a sulfur-containing, non-essential amino acid widely expressed in the mammal brain, modulates the neuronal differentiation process. In this study, we describe the effect of taurine acting via the ionotropic GABAA receptor and the metabotropic GABAB receptor on the neuronal differentiation and electrophysiological properties of precursor cells derived from the subventricular zone of the mouse brain. Taurine stimulates the number of neurites and favors the dendritic complexity of the neural precursor cells, accompanied by changes in the somatic input resistance and the strength of inward and outward membranal currents. At the pharmacological level, the blockade of GABAA receptors inhibits these effects, whereas the stimulation of GABAB receptors has no positive effects on the taurine-mediated differentiation process. Strikingly, the blockade of the GABAB receptor with CGP533737 stimulates neurite outgrowth, dendritic complexity, and membranal current kinetics of neural precursor cells. The effects of taurine on the differentiation process involve Ca2+ mobilization and the activation of intracellular signaling cascades since chelation of intracellular calcium with BAPTA-AM, and inhibition of the CaMKII, ERK1/2, and Src kinase inhibits the neurite outgrowth of neural precursor cells of the subventricular zone.


Sujet(s)
Différenciation cellulaire , Ventricules latéraux , Cellules souches neurales , Récepteurs GABA-A , Récepteurs GABA-B , Animaux , Cellules souches neurales/métabolisme , Cellules souches neurales/cytologie , Cellules souches neurales/effets des médicaments et des substances chimiques , Récepteurs GABA-B/métabolisme , Souris , Différenciation cellulaire/effets des médicaments et des substances chimiques , Récepteurs GABA-A/métabolisme , Ventricules latéraux/cytologie , Ventricules latéraux/métabolisme , Taurine/pharmacologie , Neurogenèse/effets des médicaments et des substances chimiques , Calcium/métabolisme
9.
Nutrients ; 16(12)2024 Jun 09.
Article de Anglais | MEDLINE | ID: mdl-38931171

RÉSUMÉ

Taurine, a non-proteogenic amino acid and commonly used nutritional supplement, can protect various tissues from degeneration associated with the action of the DNA-damaging chemotherapeutic agent cisplatin. Whether and how taurine protects human ovarian cancer (OC) cells from DNA damage caused by cisplatin is not well understood. We found that OC ascites-derived cells contained significantly more intracellular taurine than cell culture-modeled OC. In culture, elevation of intracellular taurine concentration to OC ascites-cell-associated levels suppressed proliferation of various OC cell lines and patient-derived organoids, reduced glycolysis, and induced cell protection from cisplatin. Taurine cell protection was associated with decreased DNA damage in response to cisplatin. A combination of RNA sequencing, reverse-phase protein arrays, live-cell microscopy, flow cytometry, and biochemical validation experiments provided evidence for taurine-mediated induction of mutant or wild-type p53 binding to DNA, activation of p53 effectors involved in negative regulation of the cell cycle (p21), and glycolysis (TIGAR). Paradoxically, taurine's suppression of cell proliferation was associated with activation of pro-mitogenic signal transduction including ERK, mTOR, and increased mRNA expression of major DNA damage-sensing molecules such as DNAPK, ATM and ATR. While inhibition of ERK or p53 did not interfere with taurine's ability to protect cells from cisplatin, suppression of mTOR with Torin2, a clinically relevant inhibitor that also targets DNAPK and ATM/ATR, broke taurine's cell protection. Our studies implicate that elevation of intracellular taurine could suppress cell growth and metabolism, and activate cell protective mechanisms involving mTOR and DNA damage-sensing signal transducti.


Sujet(s)
Cisplatine , Altération de l'ADN , Tumeurs de l'ovaire , Sérine-thréonine kinases TOR , Taurine , Protéine p53 suppresseur de tumeur , Taurine/pharmacologie , Humains , Sérine-thréonine kinases TOR/métabolisme , Femelle , Tumeurs de l'ovaire/métabolisme , Altération de l'ADN/effets des médicaments et des substances chimiques , Cisplatine/pharmacologie , Protéine p53 suppresseur de tumeur/métabolisme , Lignée cellulaire tumorale , Prolifération cellulaire/effets des médicaments et des substances chimiques , Transduction du signal/effets des médicaments et des substances chimiques , Glycolyse/effets des médicaments et des substances chimiques , Extracellular Signal-Regulated MAP Kinases/métabolisme , Antinéoplasiques/pharmacologie
10.
Nutrients ; 16(12)2024 Jun 20.
Article de Anglais | MEDLINE | ID: mdl-38931326

RÉSUMÉ

Taurine (2-aminoethanesulfonic acid) is a non-protein ß-amino acid essential for cellular homeostasis, with antioxidant, anti-inflammatory, and cytoprotective properties that are crucial for life maintenance. This study aimed to evaluate the effects of taurine administration on hippocampal neurogenesis, neuronal preservation, or reverse damage in rats exposed to forced ethanol consumption in an animal model. Wistar rats were treated with ethanol (EtOH) for a 28-day period (5% in the 1st week, 10% in the 2nd week, and 20% in the 3rd and 4th weeks). Two taurine treatment protocols (300 mg/kg i.p.) were implemented: one during ethanol consumption to analyze neuroprotection, and another after ethanol consumption to assess the reversal of ethanol-induced damage. Overall, the results demonstrated that taurine treatment was effective in protecting against deficits induced by ethanol consumption in the dentate gyrus. The EtOH+TAU group showed a significant increase in cell proliferation (145.8%) and cell survival (54.0%) compared to the EtOH+Sal group. The results also indicated similar effects regarding the reversal of ethanol-induced damage 28 days after the cessation of ethanol consumption. The EtOH+TAU group exhibited a significant increase (41.3%) in the number of DCX-immunoreactive cells compared to the EtOH+Sal group. However, this amino acid did not induce neurogenesis in the tissues of healthy rats, implying that its activity may be contingent upon post-injury stimuli.


Sujet(s)
Protéine doublecortine , Éthanol , Hippocampe , Neurogenèse , Neuroprotecteurs , Rat Wistar , Taurine , Animaux , Taurine/pharmacologie , Neurogenèse/effets des médicaments et des substances chimiques , Mâle , Neuroprotecteurs/pharmacologie , Rats , Hippocampe/effets des médicaments et des substances chimiques , Prolifération cellulaire/effets des médicaments et des substances chimiques , Gyrus denté/effets des médicaments et des substances chimiques , Neurones/effets des médicaments et des substances chimiques , Survie cellulaire/effets des médicaments et des substances chimiques , Modèles animaux de maladie humaine
11.
Nutrients ; 16(11)2024 May 23.
Article de Anglais | MEDLINE | ID: mdl-38892527

RÉSUMÉ

Taurine is a semi-essential micronutrient that acts as an anti-inflammatory molecule. The oral administration of taurine to colitic mice attenuates ongoing mucosal inflammation. This study aimed to determine whether inflammatory bowel diseases (IBDs) are marked by changes in the circulating levels of taurine. We measured the serum concentrations of taurine in 92 IBD patients [46 with ulcerative colitis (UC) and 46 with Crohn's disease (CD)] and 33 healthy controls with a commercial ELISA kit. The taurine levels were significantly decreased in both patients with UC and patients with CD compared to the controls, while there was no difference between CD and UC. Taurine levels declined with age in healthy controls but not in IBDs. IBD patients younger than 50 years had levels of taurine reduced compared to their age-matched controls. In the IBD group, taurine levels were not influenced by the body mass index of the patients and the consumption of taurine-rich nutrients, while they were significantly reduced in UC patients with clinically active disease compared to those in clinical remission. These findings indicate that IBDs are marked by serum taurine deficiency, which would seem to reflect the activity of the disease, at least in UC.


Sujet(s)
Rectocolite hémorragique , Maladie de Crohn , Maladies inflammatoires intestinales , Taurine , Taurine/sang , Humains , Mâle , Femelle , Adulte d'âge moyen , Adulte , Rectocolite hémorragique/sang , Maladie de Crohn/sang , Maladies inflammatoires intestinales/sang , Études cas-témoins , Indice de masse corporelle , Jeune adulte , Sujet âgé
12.
Folia Biol (Praha) ; 70(1): 45-52, 2024.
Article de Anglais | MEDLINE | ID: mdl-38830122

RÉSUMÉ

Effective treatment of patients with autism spectrum disorder (ASD) is still absent so far. Taurine exhibits therapeutic effects towards the autism-like behaviour in ASD model animals. Here, we determined the mechanism of taurine effect on hippocampal neurogenesis in genetically inbred BTBR T+ tf/J (BTBR) mice, a proposed model of ASD. In this ASD mouse model, we explored the effect of oral taurine supplementation on ASD-like behaviours in an open field test, elevated plus maze, marble burying test, self-grooming test, and three-chamber test. The mice were divided into four groups of normal controls (WT) and models (BTBR), who did or did not receive 6-week taurine supplementation in water (WT, WT+ Taurine, BTBR, and BTBR+Taurine). Neurogenesis-related effects were determined by Ki67 immunofluorescence staining. Western blot analysis was performed to detect the expression of phosphatase and tensin homologue deleted from chromosome 10 (PTEN)/mTOR/AKT pathway-associated proteins. Our results showed that taurine improved the autism-like behaviour, increased the proliferation of hippocampal cells, promoted PTEN expression, and reduced phosphorylation of mTOR and AKT in hippocampal tissue of the BTBR mice. In conclusion, taurine reduced the autism-like behaviour in partially inherited autism model mice, which may be associa-ted with improving the defective neural precursor cell proliferation and enhancing the PTEN-associated pathway in hippocampal tissue.


Sujet(s)
Trouble autistique , Hippocampe , Neurogenèse , Phosphohydrolase PTEN , Protéines proto-oncogènes c-akt , Transduction du signal , Sérine-thréonine kinases TOR , Taurine , Animaux , Taurine/pharmacologie , Hippocampe/métabolisme , Hippocampe/effets des médicaments et des substances chimiques , Sérine-thréonine kinases TOR/métabolisme , Phosphohydrolase PTEN/métabolisme , Protéines proto-oncogènes c-akt/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Neurogenèse/effets des médicaments et des substances chimiques , Trouble autistique/métabolisme , Trouble autistique/traitement médicamenteux , Mâle , Comportement animal/effets des médicaments et des substances chimiques , Souris , Modèles animaux de maladie humaine , Trouble du spectre autistique/métabolisme , Trouble du spectre autistique/traitement médicamenteux , Prolifération cellulaire/effets des médicaments et des substances chimiques
13.
Brain Res ; 1838: 148998, 2024 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-38754802

RÉSUMÉ

Altered extracellular amino acid concentrations following concussion or mild traumatic brain injury can result in delayed neuronal damage through overactivation of NMDA glutamatergic receptors. However, the consequences of repeated concussions prior to complete recovery are not well understood. In this study, we utilized in vivo cerebral microdialysis and a weight-drop model to investigate the acute neurochemical response to single and repeated concussions in adult rats that were fully conscious. A microdialysis probe was inserted into the hippocampus and remained in place during impact. Primary outcomes included concentrations of glutamate, GABA, taurine, glycine, glutamine, and serine, while secondary outcomes were righting times and excitotoxic indices. Compared to sham injury, the first concussion resulted in significant increases in glutamate, GABA, taurine, and glycine levels, longer righting times, and higher excitotoxic indices. Following the second concussion, righting times were significantly longer, suggesting cumulative effects of repeated concussion while only partial increases were observed in glutamate and taurine levels. GABA and glycine levels, and excitotoxic indices were comparable to sham injury. These findings suggest that single and repeated concussions may induce acute increases in several amino acids, while repeated concussions could exacerbate neurological symptoms despite less pronounced neurochemical changes.


Sujet(s)
Commotion de l'encéphale , Modèles animaux de maladie humaine , Microdialyse , Rat Sprague-Dawley , Animaux , Commotion de l'encéphale/métabolisme , Microdialyse/méthodes , Mâle , Rats , Hippocampe/métabolisme , Acide gamma-amino-butyrique/métabolisme , Taurine/métabolisme , Acide glutamique/métabolisme , Glycine/métabolisme
14.
Expert Opin Pharmacother ; 25(7): 791-799, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38814590

RÉSUMÉ

INTRODUCTION: Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, functional impairments, and neuropsychiatric symptoms. Valiltramiprosate is a tramiprosate prodrug being investigated as a novel treatment for AD. AREAS COVERED: The online databases PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched using the terms 'ALZ-801' or 'valiltramiprosate.' Alzheon press releases were reviewed for emerging clinical information. Valiltramiprosate is an oral, well-tolerated synthetic valine-conjugate prodrug of tramiprosate. Valiltramiprosate's active metabolite include tramiprosate and 3-sulfopropanoic acid. Proposed mechanism of action is multiligand binding to Aß42 which stabilizes amyloid monomers to prevent peptide aggregation and oligomerization. Pharmacokinetic studies show 52% oral bioavailability, rapid absorption, approximately 40% brain-drug exposure, and near complete renal clearance. Compared to tramiprosate, valiltramiprosate extends plasma tramiprosate half-life and improves interindividual pharmacokinetic variability. Interim analyses from valiltramiprosate's phase II biomarker trial show: (1) significant reductions in plasma p-tau181 and related AD fluid biomarkers; (2) brain structure preservation and reduced hippocampal atrophy by MRI; and (3) improvements on cognitive assessments at multiple timepoints. Its phase III clinical trial in ApoE ε4 homozygotes is near completion. EXPERT OPINION: Valiltramiprosate's clinical trial data show early indications of efficacy with potential disease modifying effect in AD.


Sujet(s)
Maladie d'Alzheimer , Promédicaments , Maladie d'Alzheimer/traitement médicamenteux , Humains , Promédicaments/pharmacocinétique , Animaux , Peptides bêta-amyloïdes/métabolisme , Cyclopropanes/usage thérapeutique , Cyclopropanes/pharmacocinétique , Cyclopropanes/pharmacologie , Cyclopropanes/administration et posologie , Association médicamenteuse , Fragments peptidiques , Biodisponibilité , Période , Valine/analogues et dérivés , Valine/pharmacocinétique , Valine/administration et posologie , Taurine/analogues et dérivés
15.
Nutr Hosp ; 41(3): 702-705, 2024 Jun 27.
Article de Espagnol | MEDLINE | ID: mdl-38726617

RÉSUMÉ

Introduction: Objectives: the prevention of central line-associated bloodstream infections is a critical aspect of care for patients with intestinal failure who are treated with parenteral nutrition. The use of taurolidine in this context is becoming increasingly popular, however there is a lack of standardization in its pediatric application. The objective of this work is to develop a guide to support its prescription. Methodology: the guide is based on a review of the literature and expert opinions from the Intestinal Failure Group of the SEGHNP. It was developed through a survey distributed to all its members, addressing aspects of usual practice with this lock solution. Results: this manuscript presents general recommendations concerning taurolidine indications, commercial presentations, appropriate forms of administration, use in special situations, adverse reactions, and contraindications in the pediatric population Conclusions: taurolidine is emerging as the primary lock solution used to prevent central line-associated bloodstream infections, proving to be safe and effective. This guide aims to optimize and standardize its use in pediatrics.


Introducción: Objetivo: la prevención de las infecciones asociadas a catéter ocupa un papel fundamental en los cuidados del paciente en situación de fracaso intestinal en tratamiento con nutrición parenteral. El empleo del sellado del catéter con taurolidina con ese fin se ha generalizado sin que exista una estandarización sobre su uso en población pediátrica. El objetivo de este trabajo es elaborar una guía clínica que sirva de apoyo en su utilización. Métodos: la guía se basa en una revisión de la literatura y en la opinión de expertos del Grupo de Trabajo de Fracaso Intestinal de la SEGHNP recogida a través de una encuesta realizada a todos sus integrantes sobre aspectos de la práctica habitual con este sellado. Resultados: este manuscrito expone unas recomendaciones en cuanto a las indicaciones, presentaciones comerciales disponibles, forma adecuada de administración, uso en situaciones especiales, reacciones adversas y contraindicaciones de la taurolidina en población pediátrica. Conclusiones: el sellado con taurolidina para la prevención de la infección asociada a catéter venoso central se ha mostrado como un tratamiento eficaz y seguro. La presente guía pretender optimizar y homogeneizar su uso en pediatría.


Sujet(s)
Insuffisance intestinale , Nutrition parentérale , Taurine , Thiadiazines , Humains , Thiadiazines/usage thérapeutique , Thiadiazines/effets indésirables , Enfant , Taurine/analogues et dérivés , Taurine/usage thérapeutique , Nutrition parentérale/normes , Nutrition parentérale/méthodes , Insuffisance intestinale/thérapie , Infections sur cathéters/prévention et contrôle , Cathétérisme veineux central/effets indésirables , Anti-infectieux/usage thérapeutique , Nourrisson , Enfant d'âge préscolaire
16.
Clin Nutr ESPEN ; 61: 203-211, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38777434

RÉSUMÉ

BACKGROUND: Taurine is considered an immunomodulatory agent. From current reports on clinical studies, we conducted a systematic review and meta-analysis to investigate the effects of taurine-enhanced enteral nutrition (EN) on the outcomes of critically ill patients to resolve conflicting evidence in literature. METHODS: Literature from PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, SINOMED, and WanFang databases were retrieved, and randomized controlled trials (RCTs) were identified. The time range spanned from January 1, 2000, to January 31, 2024. The Cochrane Collaboration Tool was used to evaluate the risk of bias. We used the GRADE approach to rate the quality of evidence and the I2 test to assess the statistical heterogeneity of the results. Risk ratio (RR), mean difference (MD), and 95% confidence interval (95% CI) were used to analyze measurement data. RESULTS: Four trials involving 236 patients were finally included. The meta-analysis results indicated that taurine-enhanced EN did not reduce mortality (RR = 0.70, p = 0.45, 95% CI [0.28, 1.80], two trials, 176 participants, low quality). There was also no significant difference in length of stay in the intensive care unit (ICU) between the taurine-enhanced EN and control groups. Taurine-enhanced EN may reduce pro-inflammatory factor interleukin-6 (IL-6) levels in critically ill patients(the result about IL-6 cannot be pooled). However, taurine-enhanced EN had no significant impact on high-sensitivity-C-reactive protein levels (MD = -0.41, p = 0.40, 95% CI [-1.35, 0.54], two trials, 60 participants, low quality). DISCUSSION: Taurine-enhanced EN may reduce IL-6 levels and is not associated with improved clinical outcomes in critically ill patients, which may have potential immunoregulatory effects in critically ill patients. Given that published studies have small samples, the above conclusions need to be verified by more rigorously designed large-sample clinical trials.


Sujet(s)
Maladie grave , Nutrition entérale , Taurine , Taurine/usage thérapeutique , Humains , Maladie grave/thérapie , Nutrition entérale/méthodes , Résultat thérapeutique , Unités de soins intensifs , Durée du séjour , Essais contrôlés randomisés comme sujet
17.
Am J Ther ; 31(4): e398-e409, 2024.
Article de Anglais | MEDLINE | ID: mdl-38710029

RÉSUMÉ

BACKGROUND: Chronic kidney disease can lead to end-stage renal disease, and the prevalence is increasing. Many patients starting hemodialysis require central venous catheters (CVCs). Catheter-related bloodstream infections (CRBSIs) are a common complication and lead to significant morbidity and mortality. Interventions to prevent CRBSI include antimicrobial lock therapy but concern for the development of antimicrobial resistance and adverse effects. Nonantimicrobial antiseptics as catheter lock solutions have also been used. Taurolidine and heparin catheter lock solution is first approved by the Food and Drug Administration for the prevention of CRBSI in patients on hemodialysis. Taurolidine has a unique mechanism of action and favorable safety profile. MECHANISM OF ACTION, PHARMACODYNAMICS, AND PHARMACOKINETICS: Taurolidine and heparin catheter lock solution have both antimicrobial and anticoagulant properties. Taurolidine is derivative of the amino acid taurine, and heparin is derived from porcine intestinal mucosa. Taurolidine not only damages microbial cell walls but also prevents the adherence of microorganisms to biological surfaces, preventing biofilm formation. Taurolidine and heparin catheter lock solution is intended to be used intraluminally within the catheter and should be aspirated. Because it is used locally, limited pharmacokinetic and pharmacodynamic data are available. CLINICAL TRIALS: The LOCK-IT-100 trial is a randomized, double-blind, phase 3 study, which included 795 end-stage renal disease patients on hemodialysis with CVC. Taurolidine and heparin was compared with the control heparin alone. The results of the study showed a 71% risk reduction in CRBSI for taurolidine and heparin arm (95% confident interval, 38%-86%, P = 0.0006). Other studies have also shown that taurolidine lock solution leads to decreased CRBSI episodes. Several systematic reviews and meta-analysis consisted of taurolidine in adult, and pediatric populations also showed reduction in the incidence of CRBSIs. THERAPEUTIC ADVANCE: Taurolidine and heparin lock solution represents a novel preventive strategy for those undergoing hemodialysis through a CVC by reducing the risk of CRBSI. This is significant progress because there are no other similar options available for patients for whom catheters are the only options for their life-saving treatment.


Sujet(s)
Anticoagulants , Infections sur cathéters , Voies veineuses centrales , Héparine , Dialyse rénale , Taurine , Thiadiazines , Taurine/analogues et dérivés , Taurine/pharmacologie , Taurine/administration et posologie , Humains , Héparine/administration et posologie , Héparine/pharmacologie , Dialyse rénale/instrumentation , Dialyse rénale/méthodes , Dialyse rénale/effets indésirables , Thiadiazines/pharmacologie , Thiadiazines/administration et posologie , Voies veineuses centrales/effets indésirables , Infections sur cathéters/prévention et contrôle , Anticoagulants/administration et posologie , Anticoagulants/pharmacologie , Cathétérisme veineux central/effets indésirables , Essais contrôlés randomisés comme sujet , Défaillance rénale chronique/thérapie , Anti-infectieux locaux/administration et posologie , Anti-infectieux locaux/pharmacologie
18.
An Acad Bras Cienc ; 96(2): e20230892, 2024.
Article de Anglais | MEDLINE | ID: mdl-38747793

RÉSUMÉ

Taurine is considered a conditionally essential amino acid for fish, so its supplementation may improve feed conversion. This study evaluated the supplementation of taurine on growth performance, hematological and immunological parameters, production costs, and survival of Nile tilapia (Oreochromis niloticus) juveniles raised in a recirculating aquaculture system (RAS). A control diet was formulated with 360 g kg-1 of crude protein without fish meal and without taurine supplementation (Control). From the control diet, another diet supplemented with 9.7 g of taurine per kg of feed (Taurine) was produced. Fish fed diet supplemented with taurine had lower daily average weight gain and final average weight compared to the control diet (p < 0.05). It was observed that taurine had no influence on condition factor, survival, or hemato-immunological parameters of Nile tilapia juveniles, but there was a higher mean corpuscular volume and greater nitrogen retention in fish from the control group (p < 0.05). It is concluded that Nile tilapia juveniles do not benefit from taurine supplementation in RAS, even when fed diet containing plant-based protein sources.


Sujet(s)
Aliment pour animaux , Aquaculture , Cichlides , Compléments alimentaires , Taurine , Animaux , Taurine/pharmacologie , Taurine/administration et posologie , Aquaculture/méthodes , Cichlides/croissance et développement
19.
PLoS One ; 19(5): e0297811, 2024.
Article de Anglais | MEDLINE | ID: mdl-38753635

RÉSUMÉ

Taurine deficiency predisposes to the development of nutritional dilated cardiomyopathy and is widespread in dogs fed with non-traditional diets. However, Golden retrievers show lower plasma taurine concentration and an impaired systolic function compared to breeds of the same size and morphotype. For these reasons, it can be difficult to classify a subject from a cardiological point of view, with the risk of considering as pathological characteristics that can be completely normal in this breed. This is a cross-sectional multicenter study. The aims were 1) to identify breed-specific range of serum taurine concentration, 2) to describe a correlation between serum taurine concentration and echocardiographic parameters of systolic function in clinically healthy Golden retrievers fed with traditional diet, 3) to identify a correlation between thyroid hormones, serum taurine concentration and echocardiographic indices. Sixty clinically healthy Golden retrievers (33% males, 67% females) were included. Fifty-three dogs were fed with traditional diets and their range of serum taurine concentration was 398.2 (31.8-430) nmol/ml. Serum taurine concentration was found to be negatively correlated to systolic internal diameter of the left ventricle and systolic and diastolic left ventricular indices and volumes obtained with different methods, whereas was positively correlated to the left ventricle ejection and shortening fractions but difference was not statistically significative. A weak but significant correlation between serum taurine and T4 was demonstrated. Serum taurine median values in dogs with normal systolic function were higher than in dogs with impaired systolic function. A cut-off of serum taurine concentration of 140.6 nmol/ml had a moderate sensitivity and specificity in the identification of an impaired left ventricular systolic function (AUC 0.6, Se 78%, Sp 44%). This study showed that the median serum taurine concentration was significantly lower in dogs with impaired systolic function. Therefore, echocardiographic monitoring is recommended in all dogs with serum taurine concentration lower than 140.6 nmol/ml.


Sujet(s)
Échocardiographie , Systole , Taurine , Hormones thyroïdiennes , Animaux , Taurine/sang , Chiens , Mâle , Femelle , Hormones thyroïdiennes/sang , Études transversales , Régime alimentaire/médecine vétérinaire , Aliment pour animaux/analyse
20.
Nutr Diabetes ; 14(1): 29, 2024 May 16.
Article de Anglais | MEDLINE | ID: mdl-38755142

RÉSUMÉ

BACKGROUND: Metabolic syndrome (MetS) is a cluster of interconnected risk factors that significantly increase the likelihood of cardiovascular disease and type 2 diabetes. Taurine has emerged as a potential therapeutic agent for MetS. This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effects of taurine supplementation on MetS-related parameters. METHODS: We conducted electronic searches through databases like Embase, PubMed, Web of Science, Cochrane CENTRAL, and ClinicalTrials.gov, encompassing publications up to December 1, 2023. Our analysis focused on established MetS diagnostic criteria, including systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C). Meta-regression explored potential dose-dependent relationships based on the total taurine dose administered during the treatment period. We also assessed secondary outcomes like body composition, lipid profile, and glycemic control. RESULTS: Our analysis included 1024 participants from 25 RCTs. The daily dosage of taurine in the studies ranged from 0.5 g/day to 6 g/day, with follow-up periods varying between 5 and 365 days. Compared to control groups, taurine supplementation demonstrated statistically significant reductions in SBP (weighted mean difference [WMD] = -3.999 mmHg, 95% confidence interval [CI] = -7.293 to -0.706, p = 0.017), DBP (WMD = -1.509 mmHg, 95% CI = -2.479 to -0.539, p = 0.002), FBG (WMD: -5.882 mg/dL, 95% CI: -10.747 to -1.018, p = 0.018), TG (WMD: -18.315 mg/dL, 95% CI: -25.628 to -11.002, p < 0.001), but not in HDL-C (WMD: 0.644 mg/dl, 95% CI: -0.244 to 1.532, p = 0.155). Meta-regression analysis revealed a dose-dependent reduction in DBP (coefficient = -0.0108 mmHg per g, p = 0.0297) and FBG (coefficient = -0.0445 mg/dL per g, p = 0.0273). No significant adverse effects were observed compared to the control group. CONCLUSION: Taurine supplementation exhibits positive effects on multiple MetS-related factors, making it a potential dietary addition for individuals at risk of or already experiencing MetS. Future research may explore dose-optimization strategies and potential long-term benefits of taurine for MetS management.


Sujet(s)
Syndrome métabolique X , Essais contrôlés randomisés comme sujet , Taurine , Taurine/usage thérapeutique , Taurine/administration et posologie , Humains , Syndrome métabolique X/sang , Syndrome métabolique X/traitement médicamenteux , Syndrome métabolique X/prévention et contrôle , Glycémie/analyse , Glycémie/effets des médicaments et des substances chimiques , Pression sanguine/effets des médicaments et des substances chimiques , Compléments alimentaires , Triglycéride/sang , Cholestérol HDL/sang , Facteurs de risque
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