TB-500

BACKGROUND: TB-500 (Ac-LKKTETQ), derived from the active site of thymosin β4 (Tβ4), has various biological functions in its unacetylated form, LKKTETQ. These functions include actin binding, dermal wound healing, angiogenesis, and skin repair. The biological effects of TB-500, however, have not been documented. And the analysis of TB-500 and its metabolites have been neither simultaneously quantified nor structurally identified using synthesized authentic standards. METHODS: This study was aimed to investigating simultaneous analytical methods of TB-500 and its metabolites in in-vitro and urine samples by using UHPLC-Q-Exactive orbitrap MS, and to comparing the biological activity of its metabolites with the parent TB-500...

Dear Editor, The costs of antipsychotic drugs (APDs) used in the treatment of mental disorders with psychosis are mentioned in treatment guidelines (APA 2021, NICE 2014). While the American Psychiatric Association guideline states that every specialist should make decisions according to the rules and conditions of their country and their region, the National Institute of Health and Clinical Excellence guideline emphasizes that drug costs must be taken into consideration in the treatment process. Classical or first-generation antipsychotic drugs (FAPDs) are relatively cheaper in terms of sales prices compared to atypical or second-generation antipsychotic drugs (SAPDs) with a slightly different effect mechanism...

The objective of this study was to examine the association of 14 variables with TB in respiratory patients. The variables included: urban/rural, persons in 1200 sqft area, TB in family, crowding, smoking (family member), gender, age, education, smoking, workplace, kitchen location, cooking fuel, ventilation, and kerosene uses. Eight hundred respiratory patients were tested for sputum positive pulmonary TB; 500 had TB and 300 did not. An analysis of the unadjusted odds ratio (UOR) and adjusted OR (AOR) was undertaken using logistic regression to link the probability of TB incidences with the variables...

The residual effect of tobacco biochar (TB ≥ 500°C) mono and co-application with Ca-hydroxide (CH), Ca-bentonite (CB) and natural zeolite (NZ) on the bio-availability of trace elements TE(s) in alkaline soils has not been deeply studied yet. A pot study that had earlier been investigated TB mono and blended with CH, CB and NZ on the immobilization of Pb, Cu Cd, and Zn by Chinese cabbage. Maize crop in the rotation was selected as test plant to assess the residual impact of amendments on stabilization of Pb, Cu Cd, and Zn in mine polluted (M-P), smelter heavily and low polluted (S-HP and S-LP, respectively) soils...

The tendency of peptides to adsorb to surfaces can raise a concern in variety of analytical fields where the qualitative/quantitative measurement of low concentration analytes (ng/mL-pg/mL) is required. To demonstrate the importance of using the optimal glassware/plasticware, four doping relevant model peptides (GHRP 5, TB-500, Insulin Lispro, Synachten) were chosen and their recovery from various surfaces were evaluated. Our experiments showed that choosing expensive consumables with low-bind characteristics is not beneficial in all cases...

Small peptides with a molecular weight of <2kDa represent a performance-enhancing substances. However, in vivo studies with human volunteers are limited because most of these peptides are not approved for human consumption. Thus, relevant in vitro models are a basic tool to study their metabolism for anti-doping purposes. To choose the best in vitro model the biotransformation of growth hormone releasing peptides (GHRPs), Desmopressin and TB-500 was investigated using various in vitro systems. High metabolic activity was observed during incubation of GHRPs and TB-500 with human kidney microsomes (HKM) and liver S9 fraction...

The analysis of low-molecular-mass peptides in doping controls has become a mandatory aspect in sports drug testing and, thus, the number of samples that has to be tested for these analytes has been steadily increasing. Several peptides <2 kDa with performance-enhancing properties are covered by the list of prohibited substances of the World Anti-Doping Agency including Desmopressin, LH-RH, Buserelin, Triptorelin, Leuprolide, GHRP-1, GHRP-2, GHRP-3, GHRP-4, GHRP-5,GHRP-6, Alexamorelin, Ipamorelin, Hexarelin, ARA-290, AOD-9604, TB-500 and Anamorelin...

Currently liquid chromatography - mass spectrometry (LC-MS) analysis after solid-phase extraction (SPE) on weak cation-exchange cartridges is a method of choice for anti-doping analysis of small bioactive peptides such as growth hormone releasing peptides (GHRPs), desmoporessin, LHRH, and TB-500 short fragment. Dilution of urine samples with phosphate buffer for pH adjustment and SPE on weak cation exchange microelution plates was tested as a means to increase throughput of this analysis. Dilution using 200 mM phosphate buffer provides good buffering capacity without affecting the peptides recoveries...

Peptide hormones represent an emerging class of potential doping agents. Detection of their misuse is difficult due to their short half-life in plasma and rapid elimination. Therefore, investigating their metabolism can improve detectability. Unfortunately, pharmacokinetic studies with human volunteers are often not allowed because of ethical constraints, and therefore alternative models are needed. This study was performed in order to evaluate in vitro models (human liver microsomes and S9 fraction) for the prediction of the metabolism of peptidic doping agents and to compare them with the established models...

With the growing availability of mature systems and strategies in biotechnology and the continuously expanding knowledge of cellular processes and involved biomolecules, human sports drug testing has become a considerably complex field in the arena of analytical chemistry. Proving the exogenous origin of peptidic drugs and respective analogs at lowest concentration levels in biological specimens (commonly blood, serum and urine) of rather limited volume is required to pursue an action against cheating athletes...

The number and diversity of potentially performance-enhancing substances is continuously growing, fueled by new pharmaceutical developments but also by the inventiveness and, at the same time, unscrupulousness of black-market (designer) drug producers and providers. In terms of sports drug testing, this situation necessitates reactive as well as proactive research and expansion of the analytical armamentarium to ensure timely, adequate, and comprehensive doping controls. This review summarizes literature published over the past 5 years on new drug entities, discontinued therapeutics, and 'tailored' compounds classified as doping agents according to the regulations of the World Anti-Doping Agency, with particular attention to analytical strategies enabling their detection in human blood or urine...

In recent years, there has been an ongoing focus for both human and equine doping control laboratories on developing detection methods to control the misuse of peptide therapeutics. Immunoaffinity purification is a common extraction method to isolate peptides from biological matrices and obtain sufficient detectability in subsequent instrumental analysis. However, monoclonal or polyclonal antibodies for immunoaffinity purification may not be commercially available, and even if available, such antibodies are usually very costly...

A veterinary preparation known as TB-500 and containing a synthetic version of the naturally occurring peptide LKKTETQ has emerged. The peptide segment (17)LKKTETQ(23) is the active site within the protein thymosin β(4) responsible for actin binding, cell migration and wound healing. The key ingredient of TB-500 is the peptide LKKTETQ with artificial acetylation of the N-terminus. TB-500 is claimed to promote endothelial cell differentiation, angiogenesis in dermal tissues, keratinocyte migration, collagen deposition and decrease inflammation...

The formulation TB-500 is suspected to be used as doping agent in sport. This work describes the detection and the identification of the N-terminal acetylated 17-23 fragment of human thymosin beta 4 (Ac-LKKTETQ) in TB-500 by means of high-performance liquid chromatography/high resolution mass spectrometry using an Orbitrap Exactive benchtop mass spectrometer. Ac-LKKTETQ was also synthesized by solid-phase peptide synthesis, and an analytical strategy for detection in plasma and urine by high-performance liquid chromatography/low resolution triple-quadrupole mass spectrometry was suggested...

Effect of hydroalcoholic extract T. bispinosa (TB) was studied on fluorescence product and biochemical parameter like lipid peroxidation, catalase activity and glutathione peroxidase activity in the brain of female albino mice. Ageing was accelerated by the treatment of 0.5 ml 5% D-galactose for 15 days. This resulted in increased fluorescence product, increase lipid peroxidation and decrease antioxidant enzyme like glutathione peroxides and catalase in cerebral cortex. After cotreatment with hydroalcoholic extract of TB (500 mg/kg, po) there was decrease in fluorescence product in cerebral cortex...

The metabolism of theobromine (TB) (500 mg per os) was determined by measuring plasma and saliva concentrations of TB and its metabolites 0-24 h after the load, and urinary excretion 0-48 h after the load. TB and its six metabolites were separated and quantified by combining high performance liquid chromatography and capillary electrophoresis. The urine analyses showed that unchanged TB accounted for 21 +/- 4% (mean +/- SD) of total excretion, the remainder being 7-methylxanthine (7-X, 36 +/- 5%), 3-methylxanthine (3-X, 21 +/- 4%), 6-amino-5[N-methylformylamino]-1-methyluracil (6-AMMU, 11 +/- 4%), 7-methyluric acid (7-U, 10 +/- 2%), 3,7-dimethyluric acid (3,7-U, 1...

STUDY OBJECTIVE: The aim was to investigate the arrhythmogenic properties of several sympathomimetic amines and their antagonism by adrenergic blocking drugs. DESIGN: Arrhythmia was induced by the investigated drugs, injected intravenously: adrenaline (ADR); noradrenaline (NA); phenylephrine (PE); isoprenaline (IP); terbutaline (Tb) and salbutamol (Sb). ADR and PE were also tested for their arrhythmogenic properties after the administration of the adrenergic antagonists propranolol, phentolamine, or both...