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PubMed2006

Preparation of optically pure tert-leucine by penicillin G acylase-catalyzed resolution.

Penicillin G acylase, from Kluyvera citrophila, was used in kinetic resolution of DL-tert-leucine. N-phenylacetylated-DL-tert-leucine, chemically synthesized from DL-tert-leucine, was enantioselctively hydrolyzed by penicillin G acylase to obtain L-tert-leucine, D-tert-leucine was prepared by acid-catalyzed hydrolysis of the remaining substrate. The total yields of D-tert-leucine and L-tert-leucine are 80.6% and 83.1%, respectively. The enantiomeric excess of the two products, D-tert-leucine and L-tert-leucine, are 98.5% and 99%. This is a practical way for the preparation of D-tert-leucine and L-tert-leucine.

Catalysis↗

PubMed1994

tert.-butyl hydroperoxide-mediated DNA base damage in cultured mammalian cells.

tert.-Butyl hydroperoxide has been utilized to study the effect of oxidative stress on living cells; however, its effect on DNA bases in cells has not been characterized. In the present work, we have investigated DNA base damage in mammalian cells exposed to this organic hydroperoxide. SP2/0 derived murine hybridoma cells were treated with 4 concentrations of tert.-butyl hydroperoxide for varying periods of time. Chromatin was isolated from treated and control cells and subsequently analyzed by gas chromatography-mass spectrometry with selected-ion monitoring for DNA base damage. Quantification of damaged DNA bases was achieved by isotope-dilution mass spectrometry. The amounts of 8 products were significantly higher than control levels in cells treated with tert.-butyl hydroperoxide at a concentration range of 0.01-0.1 mM. At concentrations from 1.0 to 10 mM, product formation was inhibited and the amounts of products were similar to those in control cells. The bimodal nature of the dose-response may be qualitatively analogous to previous reports of bimodal killing of E. coli bacteria by hydrogen peroxide. The nature of the identified DNA base lesions suggests the involvement of the hydroxyl radical in their formation. tert.-Butyl hydroperoxide is known to produce the tert.-butoxyl radical in reactions with metal ions. However, it is unlikely that the tert.-butoxyl radical produces these DNA lesions. It is suggested that DNA base damage arises from tert.-butyl hydroperoxide-mediated oxidative stress in cells, resulting in formation of hydroxyl radicals in close proximity to DNA. The inhibition of product formation at high concentrations of tert.-butyl hydroperoxide may be explained by the scavenging of tert.-butoxyl radical by tert.-butyl hydroperoxide resulting in inhibition of oxidative stress. The plausibility of the scavenging mechanism was evaluated with a mathematical simulation of the dose-response for DNA damage in solutions containing hydrogen peroxide. The simulation model predicted a bimodal dose-response which agreed qualitatively with the results in this study and with other in vivo and in vitro studies reported in the literature.

Animals↗

PubMed1967

The metabolism of the isomeric tert.-butylcyclohexanones.

1. (+/-)-2-, (+/-)-3- and 4-tert.-Butylcyclohexanone are reduced in the rabbit to secondary alcohols, which are excreted extensively conjugated with glucuronic acid. 2. The major metabolite of (+/-)-2-tert.-butylcyclohexanone is (+)-cis-2-tert.-butylcyclohexanol, which has been isolated from the urine as [(+)-cis-2-tert.-butylcyclohexyl beta-d-glucosid]uronic acid. The minor metabolite is (+)-trans-2-tert.-butylcyclohexanol. 3. (+/-)-3-tert.-Butylcyclohexanone is reduced mainly to (+/-)-cis-3-tert.-butylcyclohexanol, and to a smaller extent to (+/-)-trans-3-tert.-butylcyclohexanol. 4. 4-tert.-Butylcyclohexanone yields mainly the trans-alcohol, which is excreted in conjugated form and has been recovered from the urine as (trans-4-tert.-butylcyclohexyl beta-d-glucosid)uronic acid. The cis-alcohol is formed to a minor extent and excreted in conjugated form. 5. The ratios of the amounts of cis- to trans-alcohols produced by the three ketones differed from the relative amounts of cis- and trans-alcohols produced by the corresponding methylcyclohexanones. 6. From these findings the suggestion is made that two orientations of ketone relative to coenzyme occur: alcohols with an equatorially orientated hydroxyl group are thought to be produced as a result of a ;face-to-face' interaction with NADH, and alcohols with axially orientated hydroxyl groups as a result of a ;perpendicular' interaction. Which will predominate is thought to depend on steric factors, particularly the size and position of alkyl substituents in the substrate.

Animals↗

PubMed2003

TERT suppresses apoptotis at a premitochondrial step by a mechanism requiring reverse transcriptase activity and 14-3-3 protein-binding ability.

The catalytic subunit of telomerase (TERT) is a reverse transcriptase (RT) that adds a six-base DNA repeat onto chromosome ends and prevents their shortening during successive cell divisions. Telomerase is associated with cell immortality and cancer, which may by related to the ability of TERT to prevent apoptosis by stabilizing telomeres. However, fundamental information concerning the antiapoptotic function of TERT is lacking, including whether RT activity and/or nuclear localization are required and where telomerase acts to suppress the cell death process. Here, we show that overexpression of wild-type human TERT in HeLa cells, and in a cells lacking TERT but containing the telomerase RNA template, increases their resistance to apoptosis induced by the DNA damaging agent etoposide or the bacterial alkaloid staurosporine. In contrast, TERT mutants with disruptions of either the RT domain or a 14-3-3 binding domain fail to protect cells against apoptosis, and overexpression of TERT in cells lacking the telomerase RNA template is also ineffective in preventing apoptosis. Additional findings show that TERT suppresses apoptosis at an early step before release of cytochrome c and apoptosis-inducing factor from mitochondria. We conclude that both RT activity and 14-3-3 protein binding ability are required for the antiapoptotic function of TERT in tumor cells and that TERT can suppress a nuclear signal(s) that is an essential component of apoptotic cascades triggered by diverse stimuli.

14-3-3 Proteins↗

PubMed2006

A phase I study of the optimized cryptic peptide TERT(572y) in patients with advanced malignancies.

OBJECTIVE: It was the aim of this study to evaluate the safety of the optimized cryptic peptide TERT(572Y) in pretreated patients with advanced cancer. METHODS: Nineteen patients with progressive and chemotherapy-refractory tumors received escalated doses (2-6 mg) of 2 subcutaneous injections of the optimized TERT(572Y) peptide followed by 4 subcutaneous injections of the native TERT(572) peptide every 3 weeks. Both TERT peptides were coinjected with adjuvant Montanide ISA51. Toxicity was evaluated every 3 weeks and peptide-specific CD8+ cells were detected by flow cytometry using TERT(572Y) tetramers. RESULTS: Fourteen out of 19 patients completed the vaccination program. No grade III/IV toxicity was observed. Grade I anemia was observed in 4 patients and local skin reaction at the injection site in 11 patients. Other nonhematologic toxicities were mild, and no late toxicity was observed after a median postvaccination follow-up period of 10.7 months. There was no dose-limiting toxicity. Peripheral blood TERT(572Y)-specific CD8+ lymphocytes were detected in 13 out of 14 evaluable patients after 2 injections with the optimized TERT(572Y) peptide. There was no complete or partial response, but 4 patients (21%) with persistent TERT(572Y)-specific CD8+ experienced stable disease for a median of 10.5 months. CONCLUSION: TERT(572Y) peptide vaccine is well tolerated and effective in eliciting specific TERT(572Y) CD8+ lymphocytes in pretreated cancer patients, demonstrating that cryptic peptides could be used in cancer immunotherapy.

Adjuvants, Immunologic↗

PubMed1994

Combination of extracorporeal shock-wave lithotripsy and dissolution of gallbladder stones with methyl tert-butyl ether: a randomized study.

We conducted a prospective randomized study in gallstone patients to determine whether a combination of extracorporeal shock-wave lithotripsy and subsequent dissolution with methyl tert-butyl ether increases the success rate of methyl tert-butyl ether dissolution and shortens treatment time compared with monotherapy with methyl tert-butyl ether. Fifty patients were randomized into two groups. Twenty-five patients underwent extracorporeal shock-wave lithotripsy before contact dissolution with methyl tert-butyl ether, and 25 patients were treated with methyl tert-butyl ether alone. All patients had at least three stones or stones larger than 30 mm that were radiolucent on x-ray and had densities of less than 140 Hounsfield Units (HU) on computed tomography. Overall, the combined approach neither shortened the treatment time significantly vs. monotherapy with methyl tert-butyl ether nor reduced the time of hospitalization. The success rate was slightly but not significantly increased compared with that of methyl tert-butyl ether therapy alone. The recurrence rate was similar in the two groups after a median follow-up of 1 yr. However, when subgroups of patients with at least one stone larger than 15 mm or with stones with densities of more than 60 HU were analyzed, the clearance rate after 5 mo was significantly higher (p < 0.005 and p < 0.025, respectively) in patients subjected to a combination of extracorporeal shock-wave lithotripsy and methyl tert-butyl ether dissolution. Extracorporeal shock-wave lithotripsy and methyl tert-butyl ether did not expose patients to more adverse effects than did treatment with methyl tert-butyl ether alone.

Adult↗

PubMed2025

Aberrant TERT expression: linking chronic inflammation to hepatocellular carcinoma†.

Telomerase reverse transcriptase (TERT), the catalytic enzyme component of telomerase, plays multiple roles in cellular biology. Its canonical function is primarily associated with telomere maintenance and genomic stability. In addition, several studies revealed critical non-canonical extra-telomeric functions of TERT in various cellular processes, including cell proliferation and survival, DNA damage response, transcription, signal transduction, and metabolic regulation, both in normal and in cancer cells. Notably, TERT is aberrantly upregulated in more than 80% of hepatocellular carcinoma (HCC) cases, making it an important target in liver cancer research. However, due to the diversity and complexity of TERT's functions in vivo, the precise mechanisms by which TERT contributes to the initiation and progression of HCC remain unclear. A recent study published in The Journal of Pathology using the Alb-Cre;TertTg mouse model and clinical HCC samples addresses the role of TERT in hepatocarcinogenesis. The study demonstrates that TERT promotes cell cycle progression and hepatocarcinogenesis by enhancing NF-κB promoter activity and facilitating the ubiquitination of p21. Notably, absence of functional p53 accelerates liver tumor development in TERT transgenic mice. These findings further underscore the critical role of TERT in inflammation-driven hepatocarcinogenesis and provide new insights into its underlying mechanisms. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Telomerase↗

PubMed1993

Role of lipid peroxidation in tert-butylhydroperoxide-induced inhibition of endothelial cell calcium signaling.

The potential of lipid peroxidation in inhibition of Ca++ signaling by the membrane-permeant oxidant, tertiary butylhydroperoxide (tert-buOOH), was investigated in calf pulmonary vascular endothelial cells. The oxidant dose-dependently increased lipid peroxidation between concentrations of 10(-5) and 10(-3) M, with an ED50 of approximately 0.05 mM. In addition, the effect of tert-buOOH was time-dependent through the experimental period (3 h). Preincubation of cells with the 21-amino-steroid compound, 21-[4-(5,6-bis(diethylamino)-2-pyridinyl)-1-piperazinyl]-16 alpha-methyl-pregna-1,4,9(11)-triene-3,20-dione hydrochloride (U74500A), reduced tert-buOOH-induced lipid peroxidation to undetectable levels. The effect of U74500A was dose dependent with an IC50 of approximately 10(-6) M. Brief incubation of cells with the aminosteroid resulted in greater than 90% inhibition of lipid peroxidation during subsequent 2-h incubations with tert-buOOH and addition of U74500A during treatment of cells with tert-buOOH halted further lipid peroxidation. In contrast, the iron-containing moiety, hemin, potentiated the effect of tert-buOOH on lipid peroxidation. The ED50 of hemin was approximately 10(-6) M when cells were preincubated with this agent before treatment with tert-buOOH. The potentiating effect of hemin was time-dependent and reached a near maximum upon incubation of cells for 1 h before tert-buOOH. Preincubation of cells with U74500A before treatment with hemin and tert-buOOH decreased lipid peroxidation by 75%. Ca++ signaling was monitored in-cells loaded with the Ca(++)-sensitive fluorescent indicator, fura-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Synthesis of carbon-11-, fluorine-18-, and iodine-125-labeled GABAA-gated chloride ion channel blockers: substituted 5-tert-butyl-2-phenyl-1,3-dithianes and -dithiane oxides.

A series of substituted 5-tert-butyl-2-phenyl-1,3-dithianes and 5-tert-butyl-2-phenyl-1,1,3,3-tetraoxo-1,3-dithianes was synthesized as ligands for the GABAA receptor complex-associated neuronal chloride ion channels. The in vitro binding affinities of these compounds for the GABA-gated chloride ion channel were determined by their ability to compete with [3H]TBOB for binding to rat brain slices. Of the eight compounds tested, trans-5-tert-butyl-2-(4-cyanophenyl)-2-methyl-1,1,3,3-tetraoxo+ ++-1,3-dithiane, 9b, trans-5-tert-butyl-2-(4-fluorophenyl)-1,1,3,3-tetraoxo-1,3-dithian e, 10, and trans-5-tert-butyl-2-(4-iodophenyl)-2-methyl-1,1,3,3-tetraoxo-1,3- dithiane, 11, showed moderately high binding affinities (Ki = 41, 180, and 105 nM, respectively). Four radioligand candidates from this series, 5-tert-butyl-2-(4-cyanophenyl)-2-[11C]methyl-1,3-dithiane, [11C]6, 5-tert-butyl-2-(4-[18F]fluorophenyl)-1,3-dithiane, [18F]7, 5-tert-butyl-2-(4-[18F]-fluorophenyl)-1,1,3,3-tetraoxo-1,3- dithiane, [18F]10, and 5-tert-butyl-2-(4-[125I]iodophenyl)-2-methyl-1,1,3,3- tetraoxo-1,3-dithiane, [125I]11, have been successfully prepared for evaluation as in vivo imaging agents useful for positron emission tomography and single photon emission computed tomography. Preliminary in vivo studies indicate significant uptake into mouse brain for [18F]7, [18F]10, and [125I]11.

Animals↗

PubMed1967

The metabolism of di-(3,5-di-tert.-butyl-4-hydroxybenzyl) ether (Ionox 201) in the rat.

1. Up to one-third of a single oral dose of Ionox 201 was absorbed in rats. 2. In rats dosed with [(14)C]Ionox 201 86.8-97.2% of the label is excreted in the faeces in 24 days (much of this is eliminated in the first 4 days after dosage), 5.6% in the urine and not more than 0.8% in the exhaled air; 5.0% of (14)C is present in the carcass and viscera after removal of the gut, and most of this is in the fatty tissues. 3. About 65.0% of (14)C in the faeces is due to unchanged antioxidant, 30.0% to 3,5-di-tert.-butyl-4-hydroxybenzoic acid, 3.5% to unidentified polar constituent(s), 1.4% to 3,5-di-tert.-butyl-4-hydroxybenzaldehyde and 0.1% to 3,3',5,5'-tetra-tert.-butyl-4-,4'-stilbenequinone. A variable proportion of (14)C in the urine is due to 3,5-di-tert.-butyl-4-hydroxybenzoic acid (40-60%) and the remainder (60-40%) to the ester glucuronide, when the animals were treated with different doses of antioxidant. In eight individual animals dosed with 6.78mg. of [(14)C]Ionox 201, one-third of (14)C in the bile is due to the free acid, 45% to the ester glucuronide, 20% to an unidentified constituent and 2% to unchanged antioxidant, and, in two animals dosed with 13.56mg., there is a small proportion of free acid and a larger proportion of ester glucuronide. About 80% of (14)C in the body fat is due to unchanged antioxidant, 19% to the free acid and 1% to 3,5-di-tert.-butyl-4-hydroxybenzaldehyde. 4. At least 36.2% of a single oral dose of Ionox 201 is metabolized: 3,5-di-tert.-butyl-4-hydroxybenzoic acid accounts for 30.2% of a dose, (3,5-di-tert.-butyl-4-hydroxybenzoyl beta-d-glucopyranosid)uronic acid for 1.4%, 3,5-di-tert.-butyl-4-hydroxybenzaldehyde for 1.3%, 3,3',5,5'-tetra-tert.-butyl-4,4'-stilbenequinone for 0.1% and unidentified polar metabolite(s) for 3.2%. 5. The metabolism of Ionox 201 in vivo is closely related to its antioxidant action in vitro.

Aldehydes↗

PubMed2005

Immunohistochemical detection of telomerase reverse transcriptase (TERT) protein in benign and malignant tumor cells of the breast.

Telomerase activity is associated with immortality and is expressed in various malignant tumors. Telomerase reverse transcriptase (TERT) is a human telomerase catalytic subunit and is strongly correlated with telomerase activity. In this study, the expression of TERT was investigated by immunocytochemistry to determine whether it is a useful marker for differential diagnosis in benign or malignant breast tumors. We examined imprint smears prepared from 63 surgically resected breast lesions, and 27 cases of secretion or aspiration cytology smears had been routinely diagnosed. Eighteen of the 63 cases were examined for TERT mRNA and the correlation with expression of TERT protein was investigated. Expression of TERT protein was correlated with expression of TERT mRNA by in situ hybridization (p=0.044), suggesting that telomerase activity might be expressed with morphologic factors. In imprint smears and routine cytology smears, TERT-positive cases significantly tended to be malignant cases (p=0.014, p=0.033 respectively). Especially, in malignant imprint smear cases, positive expression of TERT was significantly correlated with lymph node metastasis (p=0.022). In conclusion, the expression of TERT protein might be a useful marker for differential diagnosis in malignant and benign breast tumors. In malignant cases, it could be a useful indicator for the assessment of potential of lymph node metastasis [corrected].

Biomarkers, Tumor↗

PubMed2002

Interaction of tert-butyl hydroperoxide with hypochlorous acid. A spin trapping and chemiluminescence study.

The formation of radical species during the reaction of ter-tbutyl hydroperoxide and hypochlorous acid has been investigated by spin trapping and chemiluminescence. A superposition of two signals appeared incubating tert-butyl hydroperoxide with hypochlorous acid in the presence of the spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN). The first signal (aN = 1.537 mT, aH beta = 0.148 mT) was an oxidation product of POBN caused by the action of hypochlorous acid. The second spin adduct (aN = 1.484 mT, aH beta = 0.233 mT) was derived from a radical species that was formed in the result of reaction of tert-butyl hydroperoxide with hypochlorous acid. Similarly, a superposition of two signals was also obtained using the spin trap N-tert-butyl-alpha-phenylnitrone (PBN). tert-Butyl hydroperoxide was also treated with Fe2+ or Ce4+ in the presence of POBN. Using Fe2+ a spin adduct with a N = 1.633 mT and aH beta = 0.276 mT was observed. The major spin adduct formed with Ce4+ was characterised by a N = 1.480 mT and aH beta = 0.233 mT. The reaction of tert-butyl hydroperoxide with hypochlorous acid was accompanied by a light emission, that time profile and intensity were identical to those emission using Ce4+. The addition of Fe2+ to tert-butyl hydroperoxide yielded a much smaller chemiluminescence. Thus, tert-butyl hydroperoxide yielded in its reaction with hypochlorous acid or Ce4+ the same spin adduct and the same luminescence profile. Because Ce4+ is known to oxidize organic hydroperoxides to peroxyl radical species, it can be concluded that a similar reaction takes place in the case of hypochlorous acid.

Electron Spin Resonance Spectroscopy↗

PubMed2026

Value of TERT promoter mutations for early outcomes in papillary thyroid cancer.

Telomerase reverse transcriptase (TERT) promoter mutations are associated with aggressive clinicopathological features of papillary thyroid cancer (PTC). However, their independent prognostic value remains unclear. This study aimed to evaluate the prognostic significance of TERT promoter mutations (TPMs) in predicting early treatment outcomes and event-free survival (EFS) in patients with PTC. We retrospectively analyzed a prospective cohort; patients underwent surgery at a single tertiary referral center between 2019 and 2022. Patients underwent thyroidectomy, selective postoperative radioactive iodine ablation, and levothyroxine suppression therapy. Propensity score matching (PSM, 1:1) was applied to adjust for baseline clinicopathological differences. Of 10,642 patients with available molecular data, 115 (1.1%) harbored TPMs. After PSM, 90 matched pairs of patients with TERT-wild-type and TERT-mutant tumors were analyzed. Early treatment responses at 1 and 2 years post-treatment and EFS were evaluated. Early treatment responses did not differ significantly between groups at 1 year (P = 0.212) and 2 years (P = 0.571). However, patients with TERT-mutant tumors had fewer excellent responses and higher rates of structural incomplete response. During follow-up, the TERT-mutant group experienced more recurrences and one disease-specific death. Cumulative EFS was significantly poorer in the TERT-mutant group than in the TERT-wild-type group (P = 0.022). Despite their low prevalence, TPMs were independently associated with adverse oncological outcomes, including higher rates of recurrence and mortality. TPMs may serve as valuable prognostic markers for early risk stratification in PTC.

Humans↗

PubMed2003

Synthesis of 3-tert-butylcatechol by an engineered monooxygenase.

Recombinant Escherichia coli JM101 was used for the in vivo biocatalytic synthesis of 3-tert-butyl- catechol. The bacterial strain synthesized the laboratory-evolved variant HbpA(T2) of 2-hydroxybiphenyl 3-monooxygenase (HbpA, EC 1.14.13.44) from Pseudomonas azelaica HBP1. The mutant enzyme HbpA(T2) is able to hydroxylate 2-tert-butylphenol to the corresponding catechol, a reaction that is not catalyzed by the wild-type enzyme. The biotransformation was performed in a 3-L bioreactor for 24 h. To mitigate the toxicity of the 2-tert-butylphenol starting material, we applied a limited substrate feed. Continuous in situ product removal with the hydrophobic resin Amberlite XAD-4 was used to separate the product from culture broth. In addition, binding to the resin stabilized the product, which was important because 3-tert-butylcatechol is very labile in aqueous solution. The productivity of the process was 63 mg L(-1) h(-1) so that after 24 h, 3.0 g of 3-tert-butylcatechol were isolated. Down-stream processing consisted of two steps. First, bound 2-tert-butylphenol and 3-tert-butylcatechol were eluted from Amberlite XAD-4 with methanol. Second, the two compounds were separated over neutral aluminum oxide, which selectively binds the produced catechol but not the phenol substrate. The final purity of 3-tert-butylcatechol was greater than 98%.

Bioreactors↗

PubMed2001

The correlation of TERT expression with c-myc expression in cervical cancer.

Recently putative catalytic telomerase subunit was identified as telomerase reverse transcriptase (TERT). Several reports showed that TERT expression correlated with telomerase activity. It has also been found that c-myc can induce telomerase activation through TERT expression. We examined expression of TERT and c-myc and their correlation in cervical cancers by reverse transcription-polymerase chain reaction (RT-PCR). It was found that TERT and c-myc expression was observed mostly in malignancies and expression of c-myc was concordant for positivity and negativity with TERT. These results support recent studies that c-myc expression is closely associated with TERT and telomerase activity. c-myc up-regulation may play an important role in activation of TERT and telomerase.

Cervix Uteri↗

PubMed1997

Effects of alpha-phenyl-tert-butyl nitrone on neuronal survival and motor function following intrastriatal injections of quinolinate or 3-nitropropionic acid.

We have investigated the neuroprotective effects of the the spin-trapping agent alpha-phenyl-tert-butyl nitrone on striatal lesions produced by local injections of the excitotoxin quinolinate or the mitochondrial toxin 3-nitropropionic acid. We have assessed both the behavioural and morphological consequences of the lesion. Thus, we tested paw-reaching ability and amphetamine- and apomorphine-induced rotational behaviour in lesioned rats with or without alpha-phenyl-tert-butyl nitrone treatment, and also explored the relationship between the outcome of the behavioural studies and the extent of the lesion. In the morphological analysis, we chose immunocytochemistry for dopamine- and cyclic AMP-regulated phosphoprotein with a molecular weight of 32,000 as a specific marker for striatal neurons. The paw-reaching ability of rats with the quinolinate and 3-nitropropionic acid lesions was significantly impaired compared to normal control animals. Treatment with alpha-phenyl-tert-butyl nitrone significantly ameliorated the paw-reaching deficits produced by the quinolinate lesion, whereas the 3-nitropropionic acid-induced deficits were unaffected by alpha-phenyl-tert-butyl nitrone. Both quinolinate and 3-nitropropionic acid lesions resulted in a rotation asymmetry towards the lesioned side in response to both amphetamine and apomorphine. In the quinolinate lesion model, the alpha-phenyl-tert-butyl nitrone treatment resulted in a less marked motor asymmetry in response to both drugs. By contrast, alpha-phenyl-tert-butyl nitrone did not significantly reduce the drug-induced rotation asymmetry in rats with a 3-nitropropionic acid lesion. Morphological analyses disclosed that alpha-phenyl-tert-butyl nitrone significantly increased the size of the spared striatum in the quinolinate lesions, but only caused a non-significant trend towards an attenuation of the 3-nitropropionic acid lesions. The behavioural deficits were inversely correlated to the size of the spared residual striatum. The intrastriatal injection of 3-nitropropionic acid, unlike the injection of quinolinate, caused degeneration of the nigrostriatal dopamine system as well as of transverse fibre bundles of the internal capsule in the striatum, in addition to the striatal lesion. The behavioural studies revealed that the combination of multiple lesions seen in 3-nitropropionic acid-lesioned rats significantly exacerbated paw-reaching deficits and amphetamine-induced rotation asymmetry. In conclusion, alpha-phenyl-tert-butyl nitrone attenuated behavioural and morphological consequences of striatal lesions induced by local injections of quinolinate, but not of 3-nitropropionic acid. Deficits in behavioural tests of striatal function reflected well the extent of striatal lesion. The intrastriatal injection of 3-nitropropionic acid led to degeneration of both intrinsic striatal neurons and the nigrostriatal dopaminergic system, suggesting that this lesion may provide an animal model of a form of multiple system atrophy rather than Huntington's disease.

Amphetamine↗

PubMed2003

High-affinity block of voltage-operated rat IIA neuronal sodium channels by 2,6 di-tert-butylphenol, a propofol analogue.

BACKGROUND AND OBJECTIVE: Propofol is a phenol derivative (2,6 di-isopropylphenol) with a unique effect profile including activating effects on GABA(A) and blocking effects on voltage-operated sodium channels. If the substituents in the 2- and the 6-positions are replaced by tert-butyl groups, the resulting phenol derivative, 2,6 di-tert-butylphenol, despite being a close structural propofol analogue, completely lacks GABA(A) receptor effects. The aim of this in vitro study was to investigate the effects of 2,6 di-tert-butylphenol on voltage-operated neuronal sodium channels in order to determine whether and, if so, how these structural changes alter the sodium channel-blocking effect seen with propofol. METHODS: Whole-cell sodium inward currents through heterologously expressed rat type IIA sodium channels were recorded in the absence and presence of definite concentrations of 2,6 di-tert-butylphenol and propofol. RESULTS: When applied at concentrations > or = 30 micromol, 2,6 di-tert-butylphenol completely and irreversibly blocked sodium inward currents. The blockade equilibrium time was about 2 min. A partial washout was possible only if the application was stopped before the equilibrium of the blockade was achieved. CONCLUSIONS: 2,6 Di-tert-butylphenol exerts a high-affinity block of neuronal sodium channels. Apparently, the slight structural differences of 2,6 di-tert-butylphenol in comparison with propofol--which account for the lack of GABA(A) receptor effects--enhance its voltage-operated sodium channel-blocking effects. As 2,6 di-tert-butylphenol is much more potent than most sodium channel blockers in clinical use, it might be of interest in the development of local anaesthetics.

Anesthetics, Intravenous↗

PubMed2002

Contact allergy to the monomers in p-tert-butylphenol-formaldehyde resin.

In many adhesive formulations p-tert-butylphenol-formaldehyde resin (PTBP-F-R) is used as a binder. Contact allergy to this resin is not rare. In patients hypersensitive to PTBP-F-R, and butylphenol derivatives therein, it is for diagnostic and preventive reasons necessary to know the nature of the primary sensitizing substances, as well as the cross-reaction patterns for these. The aim of this study was to investigate contact allergy to monomers in PTBP-F-R and potential cross-reacting substances. 12 patients hypersensitive to PTBP-F-R were patch tested with 2 monomers, the raw materials formaldehyde and p-tert-butylphenol, and 3 closely related substances. High pressure liquid chromatography (HPLC) was used to investigate the purity of the test substances. It was shown that the monomers 2-methylol p-tert-butylphenol and 2,6-dimethylol p-tert-butylphenol could elicit allergic reactions in humans hypersensitive to PTBP-F-R. No simultaneous reactions or cross-reactions were shown to formaldehyde, p-tert-butylphenol, p-tert-butylcatechol, 2(3)-tert-butyl-4-hydroxyanisole (BHA) or 3,5-di-tert-butyl-4-hydroxytoluene (BHT). It was also shown that low amounts of contaminants in the test substances, if not taken into account, could influence the conclusions drawn from the test results obtained.

Allergens↗