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1.
An Acad Bras Cienc ; 92(4): e20191311, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33237137

RESUMEN

Taurine (Tau) is an abundant amino acid in polymorphonuclear leukocytes that react with hypochlorous acid to form taurine chloramine (TauCl) under inflammatory conditions. We investigated potential interactions between lymphocytes and TauCl in rats submitted to cecal ligation. Animals were divided into sham or CLP groups (24 or 120 h) to isolate lymphocytes from blood and spleen. Lymphocytes were cultured at a concentration of 1×106 cells/mL and activated by concanavalin A. Tau and TauCl were added at 1, 10, and 100 µM. Cells were incubated with MTT to evaluate cell viability and cytokine concentration in the supernatant was determined. TauCl decreased lymphocyte viability and altered the secretion pattern of important inflammatory mediators in non-specific-phenotype manner. The effort to a is elucidate mechanisms of immune cell (dys)function in sepsis is important to better understand the complex regulation of immune system during sepsis development, and further studies are necessary to confirm TauCl as potential target in this context.


Asunto(s)
Sepsis , Bazo , Animales , Supervivencia Celular , Células Cultivadas , Citocinas , Linfocitos , Ratas , Taurina/análogos & derivados , Taurina/farmacología
2.
J Chromatogr A ; 1626: 461350, 2020 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-32797830

RESUMEN

In ionexchange chromatography, the pH gradient mode becomes more and more popular today for the analysis of therapeutic proteins as this mode can provide higher or alternative selectivity to the commonly used salt gradient mode. Ideally, a linear pH response is expected when performing linear gradients. However up to now, only a very few buffer systems have been developed and are commercially available which can perform nearly linear pH responses when flowing through a given column. It is also known that a selected buffer system (mobile phase) can work well on one column but can fail on other column. The goal of this study was to practically evaluate the effects that ionexchange columns (weak and strong exchangers) might have on effluent pH, when performing linear pH gradient separations of therapeutic monoclonal antibodies. To attain this objective, the pH was monitored on-line at the column outlet using a specific setup. To make comprehensive observations of the phenomenon, four different mobile phase conditions and five cation exchange columns (weak and strong exchangers) were employed. The obtained pH responses were systematically compared to responses measured in the absence of the columns. From this work, it has become clear that both the column and mobile phase can have significant effects on pH gradient chromatography and that their combination must be considered when developing a new method. Phase systems (column + mobile phase) providing linear pH responses are indeed the most suitable for separating mAbs with different isoelectric points and, with them, it is possible to elute mAbs across wide retention time ranges and with high selectivity.


Asunto(s)
Cromatografía por Intercambio Iónico/métodos , Anticuerpos Monoclonales/análisis , Cationes/química , Ácido Cítrico/química , Concentración de Iones de Hidrógeno , Intercambio Iónico , Fuerza Protón-Motriz , Hidróxido de Sodio/química , Taurina/análogos & derivados , Taurina/química
4.
Nutrients ; 12(4)2020 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-32316396

RESUMEN

Lactoferrin (LF) exerts a promoting bone health function. The effects of LF on bone formation at the metabolic level have been less explored. Urinary metabolic profiling of growing Sprague-Dawley (SD) rats LF-supplemented (1000 mg/kg bw) for four weeks were explored by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). The serum markers of bone formation and bone resorption, the bone mass, and the osteogenesis markers of femur were measured by an enzyme-linked immunosorbent assay, micro-computerized tomography, and immunohistochemistry, respectively. Compared with the control, LF supplementation improved bone formation (p < 0.05), reduced bone resorption (p < 0.05), enhanced femoral bone mineral density and microarchitecture (p < 0.05), and upregulated osteocalcin, osterix, and Runx-2 expression (p < 0.05) of femur. LF upregulated 69 urinary metabolites. KEGG and pathway enrichment analyses of those urinary metabolites, and the Person's correlation analyses among those urinary metabolites and bone status revealed that LF impacted on bone formation via regulatory comprehensive pathways including taurine and hypotaurine metabolism, arginine and proline metabolism, cyanoamino acid metabolism, nitrogen metabolism, nicotinate and nicotinamide metabolism, and fatty acid biosynthesis. The present study indicated the metabolomics is a useful and practical tool to elucidate the mechanisms by which LF augments bone mass formation in growing animals.


Asunto(s)
Suplementos Dietéticos , Lactoferrina/administración & dosificación , Lactoferrina/farmacología , Osteogénesis/efectos de los fármacos , Osteogénesis/fisiología , Ratas Sprague-Dawley/crecimiento & desarrollo , Animales , Arginina/metabolismo , Arginina/orina , Biomarcadores/metabolismo , Biomarcadores/orina , Cromatografía Liquida , Masculino , Metabolómica/métodos , Nitrógeno/metabolismo , Nitrógeno/orina , Prolina/metabolismo , Prolina/orina , Espectrometría de Masas en Tándem , Taurina/análogos & derivados , Taurina/metabolismo , Taurina/orina
5.
Can J Vet Res ; 84(2): 115-123, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32255906

RESUMEN

The objective of this in-vitro study was to evaluate taurolidine as a therapy for transitional cell carcinomas in canine patients. Transitional cell carcinoma (TCC) is the most common cancer of the urinary bladder in dogs and accounts for approximately 2% of reported malignancies in this species. There is no cure for this neoplasm and most dogs are lost from complications associated with progression of the local disease. Taurolidine has been shown to have anti-tumor and antiangiogenic effects against a variety of neoplasms in human and animal models. Four canine TCC cell lines were treated with various concentrations of taurolidine, mitoxantrone, and piroxicam alone. In addition, combinations of taurolidine/mitoxantrone, taurolidine/piroxicam, mitoxantrone/piroxicam, and taurolidine/mitoxantrone/piroxicam were assessed. Susceptibility of the TCC cell lines was based on a 72-hour growth inhibition assay using resazurin with absorbance measured at λ530/590. The ability of taurolidine to induce apoptosis was evaluated on 2 of the cell lines with an Annexin-V/propidium iodide assay. All cell lines were susceptible to treatment with taurolidine, mitoxantrone, and piroxicam alone. The results of the combination therapies of the 3 drugs were dependent on cell line and concentration and revealed no change in cell growth inhibition, a subadditive relationship, or a synergistic relationship. Taurolidine induced apoptosis in a concentration- and time-dependent fashion. Taurolidine alone showed significant effects on cell viability in vitro in canine TCC cell lines and these effects can be potentially enhanced with the addition of mitoxantrone and/or piroxicam.


Asunto(s)
Carcinoma de Células Transicionales/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Mitoxantrona/farmacología , Piroxicam/farmacología , Taurina/análogos & derivados , Tiadiazinas/farmacología , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma de Células Transicionales/tratamiento farmacológico , Línea Celular , Supervivencia Celular , Perros , Sinergismo Farmacológico , Mitoxantrona/administración & dosificación , Piroxicam/administración & dosificación , Taurina/administración & dosificación , Taurina/farmacología , Tiadiazinas/administración & dosificación
6.
PLoS One ; 15(4): e0231110, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32255798

RESUMEN

Infection is one of the most commonly described complications, and a major cause of morbidity and mortality in pediatric patients treated using central venous catheters (CVCs). Taurolidine lock solutions have been used to decrease catheter-related bloodstream infections (CRBSIs) in both adult and pediatric patients. The purpose of this study was to systematically search the literature and conduct a meta-analysis to determine the efficacy of taurolidine in reducing CRBSI in children. We conducted an electronic search of the PubMed, EMBASE, Cochrane Library, TRIP Database, CINAHL, and Google Scholar databases for articles published up to 1st November 2019. Eligible studies included randomized controlled trials (RCTs) comparing the effects of taurolidine with control for preventing CRBSI in pediatric patients. Four studies were included. Our results indicated a statistical significant reduction in the total number of CRBSI with taurolidine as compared to control (RR: 0.23; 95% CI:0.13, 0.40; I2 = 0%; P<0.00001). The pooled analysis also indicated a statistical significant reduction in the incidence of CRBSI (defined as the number of CRBSI events/1000 catheter days) in the taurolidine group (MD: -1.12; 95% CI:-1.54, -0.71; I2 = 1%; P<0.00001). The number of catheters removed due to infection or suspected infection was not significantly different between the two groups (RR: 0.68; 95% CI:0.22, 2.10; I2 = 56%; P = 0.50) (Fig 5). The quality of the included studies was not high. The use of taurolidine as a catheter locking solution may significantly reduce CRBSI in pediatric patients. However, the quality of current evidence is not high and further high-quality large scale RCTs are needed to corroborate our results.


Asunto(s)
Antiinfecciosos Locales/administración & dosificación , Infecciones Relacionadas con Catéteres/prevención & control , Taurina/análogos & derivados , Tiadiazinas/administración & dosificación , Infecciones Relacionadas con Catéteres/epidemiología , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/instrumentación , Catéteres Venosos Centrales/efectos adversos , Niño , Humanos , Incidencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Taurina/administración & dosificación , Resultado del Tratamiento
7.
Exp Eye Res ; 194: 107996, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-32156652

RESUMEN

Endothelin-1 (ET-1), a potent vasoconstrictor, plays a significant role in the pathophysiology of ocular conditions like glaucoma. Glaucoma is characterized by apoptotic loss of retinal ganglion cells (RGCs) and loss of visual fields and is a leading cause of irreversible blindness. In glaucomatous eyes, retinal ischemia causes release of pro-inflammatory mediators such as interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α and promotes activation of transcription factors such as nuclear factor kappa B (NFKB) and c-Jun. Magnesium acetyltaurate (MgAT) has previously been shown to protect against ET-1 induced retinal and optic nerve damage. Current study investigated the mechanisms underlying these effects of MgAT, which so far remain unknown. Sprague dawley rats were intravitreally injected with ET-1 with or without pretreatment with MgAT. Seven days post-injection, retinal expression of IL-1ß, IL-6, TNF-α, NFKB and c-Jun protein and genes was determined using multiplex assay, Western blot and PCR. Animals were subjected to retrograde labeling of RGCs to determine the extent of RGC survival. RGC survival was also examined using Brn3A staining. Furthermore, visual functions of rats were determined using Morris water maze. It was observed that pre-treatment with MgAT protects against ET-1 induced increase in the retinal expression of IL-1ß, IL-6 and TNF-α proteins and genes. It also protected against ET-1 induced activation of NFKB and c-Jun. These effects of MgAT were associated with greater RGC survival and preservation of visual functions in rats. In conclusion, MgAT prevents ET-1 induced RGC loss and loss of visual functions by suppressing neuroinflammatory reaction in rat retinas.


Asunto(s)
Glaucoma/patología , Enfermedades de la Retina/prevención & control , Células Ganglionares de la Retina/efectos de los fármacos , Taurina/análogos & derivados , Agudeza Visual , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Modelos Animales de Enfermedad , Endotelina-1/toxicidad , Femenino , Glaucoma/complicaciones , Inyecciones Intravítreas , Masculino , Pronóstico , Ratas , Ratas Sprague-Dawley , Enfermedades de la Retina/etiología , Enfermedades de la Retina/patología , Células Ganglionares de la Retina/patología , Taurina/administración & dosificación
8.
Nutrients ; 12(2)2020 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-32050544

RESUMEN

Catheter-related bloodstream infection (CRBSI) is one of the most common and potentially fatal complications in patients receiving home parenteral nutrition (HPN). In order to prevent permanent venous access loss, catheter locking with an antimicrobial solution has received significant interest and is often a favored approach as part of the treatment of CRBSI, but mainly for its prevention. Several agents have been used for treating and preventing CRBSI, for instance antibiotics, antiseptics (ethanol, taurolidine) and, historically, anticoagulants such as heparin. Nonetheless, current guidelines do not provide clear guidance on the use of catheter locks. Therefore, this review aims to provide a better understanding of the current use of antimicrobial locking in patients on HPN as well as reviewing the available data on novel compounds. Despite the fact that our current knowledge on catheter locking is still hampered by several gaps, taurolidine and ethanol solutions seem promising for prevention and potentially, but not proven, treatment of CRBSI. Additional studies are warranted to further characterize the efficacy and safety of these agents.


Asunto(s)
Antiinfecciosos/administración & dosificación , Infecciones Relacionadas con Catéteres/microbiología , Infecciones Relacionadas con Catéteres/prevención & control , Catéteres/efectos adversos , Catéteres/microbiología , Etanol/administración & dosificación , Nutrición Parenteral en el Domicilio/efectos adversos , Nutrición Parenteral en el Domicilio/instrumentación , Taurina/análogos & derivados , Tiadiazinas/administración & dosificación , Biopelículas , Humanos , Soluciones , Taurina/administración & dosificación
9.
Artículo en Inglés | MEDLINE | ID: mdl-31712211

RESUMEN

Infection of long-term central venous catheters (CVCs) remains a challenge in the clinical management of cancer patients. We aimed to determine whether a lock solution with taurolidine-citrate-heparin would be more effective than placebo for preventing nontunneled CVC infection in high-risk neutropenic hematologic patients. We performed a prospective, multicenter, randomized (1:1), double-blind, parallel, superiority, placebo-controlled trial involving 150 hematological patients with neutropenia carrying nontunneled CVCs who were assigned to receive CVC lock solution with taurolidine-citrate-heparin or heparin alone. The primary endpoint was bacterial colonization of the CVC hubs. Secondary endpoints were the incidence of catheter-related bloodstream infection (CRBSI), CVC removal, adverse events related to the lock solution, and the 30-day case fatality rate. CVC lock solution with taurolidine-citrate-heparin was associated with less colonization of the CVC hubs than that with placebo, with no statistically significant differences: 4.1%, versus 10.1% (relative risk [RR] = 0.41, 95% confidence interval [CI] = 0.11 to 1.52), with a cumulative incidence of 4.17 (95% CI = 0.87 to 11.70) and 10.14 (95% CI = 4.18 to 19.79), respectively. There were no significant differences regarding the secondary endpoints. Only three episodes of CRBSI occurred during the study period. No adverse events related to the administration of the lock solution occurred. In this trial involving high-risk patients carrying nontunneled CVCs, the use of taurolidine-citrate-heparin did not show a benefit over the use of placebo. Nevertheless, the safety of this prevention strategy and the trend toward less hub colonization in the taurolidine-citrate-heparin group raise the interest in assessing its efficacy in centers with higher rates of CRBSI. (This study has been registered in ISRCTN under identifier ISRCTN47102251.).


Asunto(s)
Infecciones Relacionadas con Catéteres/prevención & control , Catéteres Venosos Centrales/microbiología , Citratos/uso terapéutico , Neoplasias Hematológicas/complicaciones , Neutropenia/complicaciones , Cateterismo Venoso Central/efectos adversos , Método Doble Ciego , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Soluciones Farmacéuticas , Estudios Prospectivos , Taurina/análogos & derivados , Tiadiazinas
10.
Food Funct ; 11(1): 347-357, 2020 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-31799533

RESUMEN

Hypotaurine, an important sulfur-containing and nonpeptidic amino acid, is a precursor of taurine and an antioxidant. Our previous study indicated that hypotaurine levels are associated with the ageing of Caenorhabditis elegans (C. elegans). However, whether hypotaurine plays a role in the lifespan regulation of C. elegans and the mechanism remains undetermined. Here, we found that hypotaurine enhances oxidative stress resistance and ameliorates ageing in C. elegans. Our results show that hypotaurine regulates a variety of pathways and leads to the upregulation of some age-related genes to extend lifespan. We also found that the stress response-related transcription factors DAF-16/FOXO and SKN-1/NRF2 contribute to the beneficial longevity conferred by hypotaurine. Moreover, our results demonstrate that hypotaurine induced lifespan extension by regulating the insulin/IGF-1 signaling (IIS) pathway, the reproductive signaling pathway and DR-like mechanisms. Additionally, our results also indicated that mitochondrial function also plays a crucial role in the lifespan extension induced by hypotaurine. Taken together, these data indicate that hypotaurine delays the ageing of C. elegans, due, at least in part, to its antioxidant activity, which in turn regulates IIS, and reproductive and DR-related pathways, thereby inducing the activity of the transcription factors DAF-16 and SKN-1.


Asunto(s)
Caenorhabditis elegans/efectos de los fármacos , Longevidad/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Taurina/análogos & derivados , Animales , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Unión al ADN/metabolismo , Factores de Transcripción Forkhead/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Taurina/farmacología , Factores de Transcripción/metabolismo
11.
Nutrients ; 11(12)2019 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-31816880

RESUMEN

Glaucoma is a multifactorial blinding disease with a major inflammatory component ultimately leading to apoptotic retinal ganglion cell (RGC) death. Pharmacological treatments lowering intraocular pressure can help slow or prevent vision loss although the damage caused by glaucoma cannot be reversed. Recently, nutritional approaches have been evaluated for their efficacy in preventing degenerative events in the retina although mechanisms underlying their effectiveness remain to be elucidated. Here, we evaluated the efficacy of a diet supplement consisting of forskolin, homotaurine, spearmint extract, and vitamins of the B group in counteracting retinal dysfunction in a mouse model of optic nerve crush (ONC) used as an in vivo model of glaucoma. After demonstrating that ONC did not affect retinal vasculature by fluorescein angiography, we determined the effect of the diet supplement on the photopic negative response (PhNR) whose amplitude is strictly related to RGC integrity and is therefore drastically reduced in concomitance with RGC death. We found that the diet supplementation prevents the reduction of PhNR amplitude (p < 0.001) and concomitantly counteracts RGC death, as in supplemented mice, RGC number assessed immunohistochemically is significantly higher than that in non-supplemented animals (p < 0.01). Major determinants of the protective efficacy of the compound are due to a reduction of ONC-associated cytokine secretion leading to decreased levels of apoptotic markers that in supplemented mice are significantly lower than in non-supplemented animals (p < 0.001), ultimately causing RGC survival and ameliorated visual dysfunction. Overall, our data suggest that the above association of compounds plays a neuroprotective role in this mouse model of glaucoma thus offering a new perspective in inflammation-associated neurodegenerative diseases of the inner retina.


Asunto(s)
Colforsina/uso terapéutico , Mentha spicata , Traumatismos del Nervio Óptico/prevención & control , Extractos Vegetales/uso terapéutico , Taurina/análogos & derivados , Complejo Vitamínico B/uso terapéutico , Animales , Colforsina/administración & dosificación , Suplementos Dietéticos , Glaucoma/complicaciones , Ratones , Traumatismos del Nervio Óptico/etiología , Extractos Vegetales/administración & dosificación , Taurina/administración & dosificación , Taurina/uso terapéutico , Complejo Vitamínico B/administración & dosificación
12.
Rev Chilena Infectol ; 36(4): 414-420, 2019 Aug.
Artículo en Español | MEDLINE | ID: mdl-31859763

RESUMEN

Taurolidine is a broad-spectrum antiseptic used as lock therapy solution in adult and pediatric patients with long term central venous catheters (CVC) for the prevention of catheter related bloodstream infections (CRBSI). Taurolidine doesn't induce the resistant development and has only minor and brief side effects, which makes it an alternative both as a lock therapy and for the prevention of CRBSI in this group of patients.


Asunto(s)
Antiinfecciosos Locales/administración & dosificación , Infecciones Relacionadas con Catéteres/prevención & control , Catéteres Venosos Centrales/efectos adversos , Taurina/análogos & derivados , Tiadiazinas/administración & dosificación , Humanos , Taurina/administración & dosificación
13.
Proc Natl Acad Sci U S A ; 116(49): 24770-24778, 2019 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-31740614

RESUMEN

Fatty acid amide hydrolase (FAAH) degrades 2 major classes of bioactive fatty acid amides, the N-acylethanolamines (NAEs) and N-acyl taurines (NATs), in central and peripheral tissues. A functional polymorphism in the human FAAH gene is linked to obesity and mice lacking FAAH show altered metabolic states, but whether these phenotypes are caused by elevations in NAEs or NATs is unknown. To overcome the problem of concurrent elevation of NAEs and NATs caused by genetic or pharmacological disruption of FAAH in vivo, we developed an engineered mouse model harboring a single-amino acid substitution in FAAH (S268D) that selectively disrupts NAT, but not NAE, hydrolytic activity. The FAAH-S268D mice accordingly show substantial elevations in NATs without alterations in NAE content, a unique metabolic profile that correlates with heightened insulin sensitivity and GLP-1 secretion. We also show that N-oleoyl taurine (C18:1 NAT), the most abundant NAT in human plasma, decreases food intake, improves glucose tolerance, and stimulates GPR119-dependent GLP-1 and glucagon secretion in mice. Together, these data suggest that NATs act as a class of lipid messengers that improve postprandial glucose regulation and may have potential as investigational metabolites to modify metabolic disease.


Asunto(s)
Amidohidrolasas/genética , Glucemia/metabolismo , Síndrome Metabólico/metabolismo , Ácidos Oléicos/metabolismo , Taurina/análogos & derivados , Amidohidrolasas/metabolismo , Sustitución de Aminoácidos , Animales , Glucemia/análisis , Modelos Animales de Enfermedad , Ingestión de Alimentos/efectos de los fármacos , Ingestión de Alimentos/fisiología , Etanolaminas/sangre , Etanolaminas/metabolismo , Femenino , Glucagón/metabolismo , Péptido 1 Similar al Glucagón/metabolismo , Prueba de Tolerancia a la Glucosa , Humanos , Inyecciones Intravenosas , Insulina/metabolismo , Islotes Pancreáticos/efectos de los fármacos , Islotes Pancreáticos/metabolismo , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/tratamiento farmacológico , Síndrome Metabólico/genética , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Ácidos Oléicos/administración & dosificación , Ácidos Oléicos/sangre , Periodo Posprandial/efectos de los fármacos , Periodo Posprandial/fisiología , Receptores Acoplados a Proteínas G/metabolismo , Taurina/administración & dosificación , Taurina/sangre , Taurina/metabolismo
14.
Immunohorizons ; 3(10): 498-510, 2019 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-31636084

RESUMEN

Immune cells express γ-aminobutyric acid receptors (GABA-R), and GABA administration can inhibit effector T cell responses in models of autoimmune disease. The pharmacokinetic properties of GABA, however, may be suboptimal for clinical applications. The amino acid homotaurine is a type A GABA-R (GABAA-R) agonist with good pharmacokinetics and appears safe for human consumption. In this study, we show that homotaurine inhibits in vitro T cell proliferation to a similar degree as GABA but at lower concentrations. In vivo, oral homotaurine treatment had a modest ability to reverse hyperglycemia in newly hyperglycemic NOD mice but was ineffective after the onset of severe hyperglycemia. In severely diabetic NOD mice, the combination of homotaurine and low-dose anti-CD3 treatment significantly increased 1) disease remission, 2) the percentages of splenic CD4+and CD8+ regulatory T cells compared with anti-CD3 alone, and 3) the frequencies of CD4+ and CD8+ regulatory T cells in the pancreatic lymph nodes compared with homotaurine monotherapy. Histological examination of their pancreata provided no evidence of the large-scale GABAA-R agonist-mediated replenishment of islet ß-cells that has been reported by others. However, we did observe a few functional islets in mice that received combined therapy. Thus, GABAA-R activation enhanced CD4+and CD8+ regulatory T cell responses following the depletion of effector T cells, which was associated with the preservation of some functional islets. Finally, we observed that homotaurine treatment enhanced ß-cell replication and survival in a human islet xenograft model. Hence, GABAA-R agonists, such as homotaurine, are attractive candidates for testing in combination with other therapeutic agents in type 1 diabetes clinical trials.


Asunto(s)
Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD8-positivos/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Agonistas del GABA/farmacología , Agonistas del GABA/uso terapéutico , Muromonab-CD3/uso terapéutico , Taurina/análogos & derivados , Animales , Glucemia/efectos de los fármacos , Diabetes Mellitus Experimental/inmunología , Diabetes Mellitus Tipo 1/inmunología , Sinergismo Farmacológico , Femenino , Humanos , Células Secretoras de Insulina/efectos de los fármacos , Trasplante de Islotes Pancreáticos , Ratones Endogámicos NOD , Ratones SCID , Muromonab-CD3/farmacología , Taurina/farmacología , Taurina/uso terapéutico
15.
Adv Exp Med Biol ; 1155: 61-70, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31468386

RESUMEN

Taurine is an abundant sulfur-containing amino acid in myeloid cells. It undergoes halogenation in activated phagocytes and is converted to taurine chloramine (TauCl) and taurine bromamine. Bone homeostasis is mediated by the balance between bone-forming osteoblasts and bone-resorbing osteoclasts. Osteoclasts are bone-resorbing multinucleated cells differentiated from monocyte/macrophage precursor cells in response to receptor activator of NF-κB ligand (RANKL). In this study, we investigated the effect of TauCl on RANKL-induced osteoclastogenesis from RAW 264.7 macrophages. TauCl inhibited the formation of multi-nucleated osteoclast and the activity of tartrate-resistant acid phosphatase (TRAP). TauCl decreased the mRNA expression of osteoclast markers, such as TRAP, cathepsin K, and calcitonin receptor. TauCl also inhibited expression of the transcription factors, c-Fos and nuclear factor of activated T cells, which are important for osteoclast differentiation. These results suggest that TauCl might be used as a therapeutic agent to treat bone diseases associated with excessive bone resorption.


Asunto(s)
Diferenciación Celular , Osteoclastos/efectos de los fármacos , Taurina/análogos & derivados , Animales , Ratones , Ligando RANK/fisiología , Células RAW 264.7 , Transducción de Señal , Fosfatasa Ácida Tartratorresistente/fisiología , Taurina/farmacología , Factores de Transcripción/fisiología
16.
Adv Exp Med Biol ; 1155: 755-771, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31468446

RESUMEN

In the last decade thiotaurine, 2-aminoethane thiosulfonate, has been investigated as an inflammatory modulating agent as a result of its ability to release hydrogen sulfide (H2S) known to play regulatory roles in inflammation. Thiotaurine can be included in the "taurine family" due to structural similarity to taurine and hypotaurine, and is characterized by the presence of a sulfane sulfur moiety. Thiotaurine can be produced by different pathways, such as the spontaneous transsulfuration between thiocysteine - a persulfide analogue of cysteine - and hypotaurine as well as in vivo from cystine. Moreover, the enzymatic oxidation of cysteamine to hypotaurine and thiotaurine in the presence of inorganic sulfur can occur in animal tissues and last but not least thiotaurine can be generated by the transfer of sulfur from mercaptopyruvate to hypotaurine catalyzed by a sulfurtransferase. Thiotaurine is an effective antioxidant agent as demonstrated by its ability to counteract the damage caused by pro-oxidants in the rat. Recently, we observed the influence of thiotaurine on human neutrophils functional responses. In particular, thiotaurine has been found to prevent human neutrophil spontaneous apoptosis suggesting an alternative or additional role to its antioxidant activity. It is likely that the sulfane sulfur of thiotaurine may modulate neutrophil activation via persulfidation of target proteins. In conclusion, thiotaurine can represent a biologically relevant sulfur donor acting as a biological intermediate in the transport, storage and release of sulfide.


Asunto(s)
Sulfuro de Hidrógeno , Taurina/análogos & derivados , Animales , Antioxidantes/farmacología , Apoptosis , Humanos , Neutrófilos/citología , Neutrófilos/efectos de los fármacos , Ratas , Transducción de Señal , Sulfuros , Taurina/fisiología
17.
Adv Exp Med Biol ; 1155: 1015-1031, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31468464

RESUMEN

Taurine haloamines (N-chlorotaurine, N-bromotaurine) due to their strong antiseptic and anti-inflammatory properties are good candidates for topical application in treatment of skin inflammatory/infectious disorders. Recently, we have demonstrated that more stable N-bromotaurine analogs (N-dibromo-dimethyl taurine, N-monobromo-dimethyl taurine) and bromamine T show strong microbicidal and anti-inflammatory properties at concentrations well tolerated by human cells and tissue. Non-steroidal anti-inflammatory drugs (NSAIDs) with cyclooxygenase (COX) inhibitory activity are commonly used in various inflammatory diseases. However, systemic administration of NSAIDs may result in adverse side effects. For example, the use of ibuprofen in children with varicella is associated with enhanced serum levels of TNF-α and with increased risk of necrotizing soft tissue infections and secondary skin infections caused by invasive streptococci. The aim of this study was to examine combined immunomodulatory effects of bromamines and ibuprofen on J774.A1 macrophages. We have shown that the primary activity of ibuprofen, the inhibition of PGE2 production by activated macrophages was intensified in the presence of bromamines. Most importantly, the stimulatory effect of ibuprofen on production of inflammatory cytokines (TNF-α, IL-6) was inhibited by all tested bromamines. These observations indicate that bromamines may neutralize massive production of TNF-α at sites of inflammation, a side effect of ibuprofen. Therefore, we suggest that systemic administration of ibuprofen (NSAIDs) in treatment of inflammatory/infectious skin diseases should be supported by topical application of bromamines as an adjunctive therapy.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Ibuprofeno/farmacología , Macrófagos/efectos de los fármacos , Taurina/análogos & derivados , Línea Celular , Citocinas/metabolismo , Dinoprostona/metabolismo , Humanos , Taurina/farmacología
18.
Adv Exp Med Biol ; 1155: 1033-1048, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31468465

RESUMEN

The stable N-bromotaurine analogs (N-dibromo-dimethyl taurine, N-monobromo-dimethyl taurine), and bromamine T (BAT) show anti-inflammatory and microbicidal properties. These bromamines are good candidates for a treatment of skin infectious/inflammatory diseases as local antiseptics. Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is commonly used in various infectious/inflammatory diseases due to its analgesic and antipyretic therapeutic effects. However, systemic administration of ibuprofen may also result in adverse side effects. It has been reported that ibuprofen enhances serum levels of TNF-α and worsens secondary skin infections caused by invasive streptococci (S. pyogenes). Recently we have demonstrated that bromamines inhibit the stimulatory effect of ibuprofen on the production of inflammatory cytokines (TNF-α, IL-6). The aim of this study was to examine the combined antibacterial actions of ibuprofen and bromamines against S. pyogenes and their joint effect on the generation of reactive oxygen species (ROS) by activated neutrophils and macrophages. We have shown that the microbicidal activity of bromamines against S. pyogenes was not altered by ibuprofen. On the other hand, co-administration of ibuprofen and bromamines markedly decreased the generation of ROS by activated neutrophils and macrophages. Finally, we discuss how the antioxidant combined effect of bromamines and ibuprofen may affect a local defense system.


Asunto(s)
Antibacterianos/farmacología , Ibuprofeno/farmacología , Macrófagos/efectos de los fármacos , Neutrófilos/efectos de los fármacos , Streptococcus pyogenes/efectos de los fármacos , Taurina/análogos & derivados , Antioxidantes/farmacología , Células Cultivadas , Humanos , Especies Reactivas de Oxígeno/metabolismo , Taurina/farmacología
19.
PLoS One ; 14(8): e0220712, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31404085

RESUMEN

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious adverse event of bone-modifying agents used to prevent bone complications in cancer patients with bone metastasis. Currently, early treatment is the only way to prevent further progression, as the pathogenesis of MRONJ has not yet been elucidated, and a standard treatment has not been established. The aim of this study was to identify a marker for early detection marker of MRONJ by exploring substances in saliva specific to MRONJ at an early stage. We collected salivary samples from 17 patients with MRONJ and conducted metabolomic analyses using capillary electrophoresis mass spectrometry for non-targeted analysis of hydrophilic metabolites. In the screening cohort, we compared the saliva of patients with stage ≥1 advanced MRONJ (n = 9) with that of controls without MRONJ before chemotherapy (n = 9). The top 5 most elevated salivary metabolites were histamine, 3-(4-hydroxyphenyl)propionate, malonate, carnosine, and hypotaurine. In the validation cohort, we analyzed additional patients with stage ≥1 advanced MRONJ (n = 8) and controls without MRONJ after chemotherapy (n = 9), confirming a significant 2.28-fold elevation in the salivary concentration of hypotaurine. These results revealed elevated salivary hypotaurine concentration as a potential marker for the early detection of MRONJ.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico , Saliva/química , Taurina/análogos & derivados , Anciano , Biomarcadores/análisis , Osteonecrosis de los Maxilares Asociada a Difosfonatos/metabolismo , Estudios de Casos y Controles , Electroforesis Capilar , Femenino , Humanos , Masculino , Espectrometría de Masas , Metabolómica , Persona de Mediana Edad , Taurina/análisis
20.
J Microbiol Biotechnol ; 29(8): 1221-1229, 2019 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-31370112

RESUMEN

Mycobacterium tuberculosis, a causative pathogen of tuberculosis (TB), still threatens human health worldwide. To find a novel drug to eradicate this pathogen, we tested taurine-5- bromosalicylaldehyde Schiff base (TBSSB) as an innovative anti-mycobacterial drug using Mycobacterium smegmatis as a surrogate model for M. tuberculosis. We investigated the antimicrobial activity of TBSSB against M. smegmatis by plotting growth curves, examined the effect of TBSSB on biofilm formation, observed morphological changes by scanning electron microscopy and transmission electron microscopy, and detected differentially expressed proteins using two-dimensional gel electrophoresis coupled with mass spectrometry. TBSSB inhibited mycobacterial growth and biofilm formation, altered cell ultrastructure and intracellular content, and inhibited cell division. Furthermore, M. smegmatis adapted itself to TBSSB inhibition by regulating the metabolic pathways and enzymatic activities of the identified proteins. NDMA-dependent methanol dehydrogenase, NAD(P)H nitroreductase, and amidohydrolase AmiB1 appear to be pivotal factors to regulate the M. smegmatis survival under TBSSB. Our dataset reinforced the idea that Schiff base-taurine compounds have the potential to be developed as novel anti-mycobacterial drugs.


Asunto(s)
Aldehídos/farmacología , Antibacterianos/farmacología , Mycobacterium smegmatis/efectos de los fármacos , Proteómica , Bases de Schiff/farmacología , Taurina/análogos & derivados , Proteínas Bacterianas/efectos de los fármacos , Biopelículas/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Pared Celular/efectos de los fármacos , Redes y Vías Metabólicas/efectos de los fármacos , Mycobacterium smegmatis/crecimiento & desarrollo , Mycobacterium smegmatis/ultraestructura , Mycobacterium tuberculosis , Taurina/farmacología
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