Thiamine Tetrahydrofurfuryl Disulfide Research Articles

Clinical and biochemical findings in bovine cerebrocortical necrosis produced by oral administration of amprolium.

Purposing to get some hints on cause and early diagnosis for cerebrocortical necrosis (CCN), CCN was produced in three healthy calves by the oral administration of amprolium. All three calves showed central nervous signs characterized by ataxic gait, clonic spasm, astasia and opisthotonus, from 24 to 49 days after the start of daily administration of 321-418 mg/kg amprolium. They showed bradycardia from about 20 days before the appearance of the nervous signs, which was supposed to be a finding of primary change and to be useful for early diagnosis of CCN. At necropsy of the two calves, large necrotic lesion was found in the cerebral cortex, and tissue thiamine levels decreased significantly, especially in cerebrum and cerebellum. In the other calf, injection with 25 mg thiamine tetrahydrofurfuryl disulfide (TTFD) was proved to be effective for the recovery of clinical signs. No significant changes in thiamine level were recorded in the whole blood, but those in erythrocytes decreased slightly at about a week before the appearance of the clinical signs. No significant alteration of thiamine excretion was observed in urine. Those findings suggest that CCN in calves is caused by thiamine deficiency and that the blood thiamine levels cannot be used for diagnosis of CCN.

Inhibition by Thiamine Tetrahydrofurfuryl Disulfide (TTFD) of the Arachidonic Acid Cascade-Line Activation as Evidenced in the Heart-Lung Preparation of the Dog

The effects of thiamine tetrahydrofurfuryl disulfide (TTFD) on the gradual increase in the coronary blood flow (CBF) inherent in the canine heart-lung preparation were studied. TTFD is a disulfide-type derivative of thiamine reported to have an antiinflammatory effect in experimental animals. Since it was found that the substance could reverse the gradual increase in CBF, the possibility that the reversal was brought about through an inhibition of activation of the arachidonic acid cascade-line was tested, examining the effects of this substance on the CBF increase produced by arachidonic acid (AA) and prostacyclin (PGI2). The vasodilator response to AA, which was barely detectable at the start of the experiment at which CBF was at a physiological low level, became potentiated as the gradual increase in CBF occurred, returning to the initial magnitude after TTFD, while the vasodilator response to PGI2 remained essentially unchanged during the entire course of the experiment. It was concluded that TTFD reversed the gradual increase in CBF in the HLP through the inhibition of the arachidonic acid cascade-line activation.

Effect of thiamine tetrahydrofurfuryl disulfide on audiogenic seizures in DBA/2J mice.

Weanling mice of the DBA/2J strain are spontaneously audiogenically seizure prone between 19 and 24 days. Thereafter, susceptibility declines rapidly within the next 7-10 days. It was found that thiamine tetrahydrofurfuryl disulfide (TTFD) significantly delayed the natural disappearance of seizure proneness in male animals compared with controls treated with identical doses of saline. There was no significant difference between treated females and controls. Evidence is presented that suggests that TTFD is cholinergic in its action and has pharmacologic effects other than a simple vitamin replacement. The difference between males and females found in this strain of mouse in this experiment is consistent with previous information which indicates that sex-related differences exist in their response to stress.

Deficiency of Dihydrolipoyl Dehydrogenase (a Component of the Pyruvate and α-Ketoglutarate Dehydrogenase Complexes): A Cause of Congenital Chronic Lactic Acidosis in Infancy

A male child died at 7 months of age with progressive neurologic deterioration and persistent metabolic acidosis. Investigations during life showed this child to have elevated blood pyruvate, lactate, and alpha-ketoglutarate as well as elevation of branched chain amino acids and occasional hypoglycemia. Cofactor therapy using either thiamine-HCl (2 g/kg/24 hr) or thiamine tetrahydrofurfuryl disulfide had no measurable effect on the clinical or biochemical status of the patient. Tissue taken postmortem showed normal levels of key gluconeogenic enzymes but a deficiency in the activity of pyruvate dehydrogenase in all tissues tested (liver, brain, kidney, skeletal muscle, and heart). Examination of the individual activities of pyruvate dehydrogenase complex showed pyruvate decarboxylase (E1) to be normal in liver and other tissues. Dihydrolipoyl dehydrogenase (E3), on the other hand, was deficient in all tissues tested. alpha-Ketoglutarate dehydrogenase complex, which depends of E3 for its total activity, was also deficient in all tissues tested. The absence of this enzyme id discussed in relation to the clinical and biochemical status of the patient.

Effect of Thiamine Propyl Disulfide, Thiamine Tetrahydrofurfuryl Disulfide and p-Chloromercuriphenyl Sulfonic Acid on the Spontaneous Beating of Cultured Mouse Myocardial Cells

Effect of Thiamine Propyl Disulfide, Thiamine Tetrahydrofurfuryl Disulfide and p-Chloromercuriphenyl Sulfonic Acid on the Spontaneous Beating of Cultured Mouse Myocardial Cells

Effects of thiamine administration on blood lactic and concentration and mineral metabolism in sheep.

The object of the present experiment is to determine the effect of thiamine administration on lactic acid concentration in blood plasma and the mineral metabolism in sheep given low and high concentrate rations. A high concentrate ration containing 90% concentrate and 10% roughage was fed to one group of sheep and a low concentrate ration containing 60% concentrate was given to the other group. Thiamine was intramuscularly injected into every sheep at a level of 50 mg of thiamine tetrahydrofurfuryl disulfide per day. No great difference was found in the plasma lactic acid concentration between the animals fed the low and high concentrate rations, and those between the control and thiamine injection periods. Thiamine injection appeared to increase urine and fecal magnesium excretion and significantly decreased magnesium balance (p less than 0.05). It may be conceivable that endogenous magnesium excretion is enhanced by thiamine administration in sheep.

Effects of low temperature and electrical (square wave) stimulation on spontaneous contractions in isolated guinea pig atria and influence of thiamine tetrahydrofurfuryl disulfide (TTFD) on these effects.

The spontaneous contractions of isolated guinea pig atria were arrested by a temperature change in the medium for 30 to 20 degrees C within 20 min. 2. When thiamine tetrahydrofurfuryl sulfide (TTFD) at concentration of 10-5 g/ml was added in the medium, the arrest was not seen for more than 30 min. 3. Arrhythmic contractions induced by the electrical square wave stimulation of threshold intensity were prevented by TTFD at 10-4 g/ml which was added to the medium. 4. These effects of TTFD at respective concentrations were seen even 30 min after the drug was removed from the medium, when the atria had been pre-incubated with the drug for one hour before the removal. 5. From these results, it was assumed that TTFD might show these effects against the extrinsic physical invasions through the stabilization of the tissue membrane.

Cardiac action of thiamine derivatives in guinea pig atria.

Pharmacological studies were performed on allithiamine (TAD), thiamine propyl disulfide (TPD), and thiamine tetrahydrofurfuryl disulfide (TTFD) to investigate positive inotropic and negative chronotropic effects seen when they are applied to spontaneous beats in isolated guinea pig atria at concentrations higher than 10-5 g/ml. 1. The effects of thiamine 8-(methyl-6-acetyldihydrothioacetate) disulfide (TATD) and thiamine hydroxyethyl disulfide (TOED) at 5 x 10-4 were slight, and those of dibenzoyl thiamine (DBT) and thiamine were limited at any concentration. 2. Dimethyl propyl disulfide (DMPD) which has anti-thiamine activity, showed these effects at concentrations higher than 10-5. 3. The negative chronotropic effect of TAD, TPD, and TTFD was not influenced by the prior application of atropine, and the positive inotropic effect was not influenced by propranolol. 4. The effects of TTFD on the electrically driven left atrial muscle were remarkable when the muscle was driven at low frequency, while they were less remarkable at high frequency. 5. The decrease in tension of the electrically driven left atria induced by mersalyl at 5 x 10-4 g/ml was recovered by the subsequent addition of TTFD or TPD at 5 x 10-4 as well as dimercaprol at 5 x 10-5. From the results, it was assumed that (a) the effects of TAD, TPD and TTFD might relate to their common chemical structure of the disulfide, especially to the alkyldisulfide chain, (b) the effects are irrevelant to their common activity as an vitamin B1 and to either cholinergic or adrenergic effect, and (c) a mutual dependence is seen between the positive inotropic effect and the negative chronotropic effect.

Ultracytochemical studies on the effects of thiamine and thiamine tetrahydrofurfuryl disulfide on acetylcholinesterase activity in guinea pig atria.

As a result of histological and ultracytochemical investigations concerning the influence of thiamine and its disulfide derivative, thiamine tetrahydrofurfuryl disulfide (TTFD), on acetylcholinesterase (AChE) in extirpated guinea pig atria, it was found that there was a clear increase in the AChE activity by 10(-4) M TTFD, a weak increase with 10(-5) M and an extremely weak increase, about the same as that in only the nutrient (Locke's solution), with 5 x 10(-4) M. However, with 10(-4) M of thiamine there was a tendency for the activity to be the same degree as with Lock's solution alone or be even inhibited at times.

Absorption, utilization and clinical effectiveness of allithiamines compared to water-soluble thiamines.

Oral administration of lipid-soluble allithiamines [thiamine propyl disulfide (TPD) and thiamine tetrahydrofurfuryl disulfide (TTHF)] rapidly increased thiamine activity in whole blood, red blood cells, cerebrospinal fluid, and urine in normal and thiamine-deficient subjects. These thiamine congeners also restored red blood cell transketolase to normal in alcoholics with thiamine deficiency. Such repletion equaled that produced by parenteral, water-soluble thiamine hydrochloride (THCl) or thiamine pyrophosphate (TPP). Oral administration of water-soluble thiamines (THCl, TPP) neither elevated thiamine activity in biological fluids nor restored transketolase activity to normal in alcoholics with thiamine deficiency presumably due to their rate-limited intestinal transport. Oral administration of TPD eliminated lateral rectus palsy in patients with Wernicke's encephalopathy. Orally administered allithiamine vitamers are therefore recommended for prophylaxis and treatment of thiamine deficits because while having essentially the same biological properties as parenterally administered water-soluble thiamines they have not produced any untoward effects after long-term administration and are far more efficiently utilized.

モルモット摘出心房律動に対する低温および矩形波電気刺激の効果と,これに及ぼすThiamine tetrahydrofurfuryl-disulfide(TTFD)の影響

モルモット摘出心房律動に対する低温および矩形波電気刺激の効果と,これに及ぼすThiamine tetrahydrofurfuryl-disulfide(TTFD)の影響

Observations on the development of antibodies to thiamine tetrahydrofurfuryl disulfide in rabbits.

Studies were conducted to determine if oral and intravenous administration of thiamine tetrahydrofurfuryl disulfide (TTFD) resulted in the development of antibodies specific to TTFD. In addition, attempts were made to elicit an antigenic response to protein-coupled TTFD emulsified in complete Freund’s adjuvant and administered via foot pad and multiple subcutaneous site injections. From 160 separate assays no TTFD-specific antibodies were detected.

Enzymatic studies on the metabolism of the tetrahydrofurfuryl mercaptan moiety of thiamine tetrahydrofurfuryl disulfide. IV. Induction of microsomal S-transmethylase, and sulfide and sulfoxide oxygenases in the drug-treated rat.

Enzymatic studies on the metabolism of the tetrahydrofurfuryl mercaptan moiety of thiamine tetrahydrofurfuryl disulfide. IV. Induction of microsomal S-transmethylase, and sulfide and sulfoxide oxygenases in the drug-treated rat.

The effect of VB1 and its derivatives on the respiration of the isolated rat liver mitochondria.

The effect of thiamine and its various derivatives on the respiratory control of rat liver mitochondria was examined. Except TDP all other thiamine derivatives tested were shown to damage mitochondrial respiration. In these experiments DCET and T A TD are shown to be strong inhibitors. It was noted that thiamine and its derivatives except TDP have aldehyde group in their chemical structure. Because formaldehyde and acetalhyde are inhibitors to the respiration of the isolated rat liver mitochondria, the aldehyde group in chemical structure is speculated to have some relation to their action on liver mitochondria. Further studies are necessary concerning the mechanism of the inhibitory actions of thi!lmine derivatives. INTRODUCTION Many thiamine derivatives are at present widely used in Japan by clinicians in place of thiamine. Except thiamine diphosphate, thiamine derivatives used in Japan have an aldehyde group in their chemical structure. It is well known that formaldehyde and acetaldehyde are inhibitors to the respiration by isolated rat liver mitochondria1>. The effect of thiamine derivatives on the mitochondrial functions must be an interesting problem to be studied. Muraoka has reported that TPD and TTFD decreased respiratory control of the isolated rat liver mitochondria. He suspected that Pi in the reaction medium and SH group in their chemical structure have some relation to this effect 2>. In the present report we examined the effect of thiamine and its seven derivates including TPD and TTFD on the respiration of isolated rat liver mitochondria and we recognized that all derivatives except TDP impaired Jl9f 3Z ~ Received for publication September 8, 1972. Thiamine: Bt TDP : Thiamine diphosphate TPD : Thiamine propyldisulfide TTFD BUTDS BTMP DCET TATD Thiamine tetrahydrofurfuryl disulfide o-butyroyl thiamine disulfide s-benzoyl thiamine monophosphate o, s-diethoxycarbonyl thiamine Thiamine methyl-6-acetyl-dihydrothioacetate disulfide

Biotransformation of thiamine tetrahydrofurfuryldisulfide and its effect on potassium loss in isolated guinea-pig atria.

In our previous paper, the authors had reported that the reduction in potassium content in isolated guinea-pig atria, kept in a potassium-free medium was prevented by thiamine tetrahydrofurfuryldisulfide (TTFD), added to the medium. In the present experiment, the attempt was to clarify whether or not this drug effect was caused by a biosynthetic thiamine originating from the TTFD. The effect of TTFD was observed in atria which had been treated once with TTFD, then washed out with Locke's solution, and finally subjected to a medium containing a low concentration of potassium ions without TTFD. As this effect seemed to be due to some biosynthetic compound originating from the TTFD, the amounts of thiamine in both the free and the bound forms were chemically estimated. A direct relation, however, could scarcely be found between the effect of TTFD and the amount of biosynthetic thiamine. The effect of TTFD was therefore assumed to be produced by the biotransformation of TTFD in the atria.

THE INFLUENCE OF THIAMINE TETRAHYDROFURFURYLDISULFIDE AGAINST STROPHANTHIN-G TOXICITY IN GUINEA-PIG ATRIA

An investigation was made as to whether or not strophanthin-G toxicity against isolated guinea-pig atria would be reduced by thiamine tetrahydrofurfuryldisulfide (TTFD), the degree of toxicity being estimated by the time required for the drug to arrest atrial contraction. Strophanthin-G in toxic dosage had been found to decrease potassium content and increase sodium content in atrial tissue. When TTFD and strophanthin-G were given to the atria at the same time, the toxicity of the latter was reduced, and the decrease in potassium content was prevented, but the increase in sodium content was scarcely influenced. Similar effects of TTFD were seen even when the added TTFD had been removed from the bath fluid after it had once influence on strophanthin-G toxicity. These results led to a discussion on the action mechanism of TTFD against strophanthin-G toxicity on isolated atria.

The active groups in the structure of thiamine tetrahydrofurfuryldisulfide in its anti-potassium, anti-quinidine, and anti-acetylcholine effects on guinea-pig atria.

Anti-potassium, anti-quinidine, and anti-acetylcholine effects of thiamine tetrahydrofurfuryldisulfide (TTFD) on isolated guinea-pig atria were compared with those of thialium, dimethialium, dimethiamine propyldisulfide (DMPD), oxythiamine, and oxythiamine propyldisulfide (OTPD). From the different effects of these thiamine derivatives having different chemical structures, the following findings were obtained in relation to their possible active atom groups in above effects.1) TTFD and DMPD showed an anti-potassium effect on the spontaneous contractions; this action may be caused by atom groups common to their chemical structures, that is, the presence of an S-S bond and presumedly also of a pair of nitrogen atoms, one of which is in a 4-amino group in a pyrimidine ring and the other of which is in an open thiazole ring at a distance of about 4 ångström from the first.2) TTFD and DMPD showed an anti-quinidine effect on the atrial contractions.3) In its high concentrations, DMPD depressed the sino-atrial node activity.4) The anti-acetylcholine effect of thiamine related compounds tested may be due to the fact that they have neither an S-S bond nor an amino group in their pyrimidine rings.5) The anti-potassium, anti-quinidine effects of thiamine were weak, while those of the thiamine derivatives such as TTFD and DMPD were remarkable because of the presence of an S-S bond which may promote an affinity of the thiamine molecule for atria.

The effect of thiamine tetrahydrofurfuryldisulfide against potassium loss in isolated guinea-pig atria.

Spontaneous contractions of isolated guinea-pig atria were arrested in a potassium free medium. But, the time required to arrest atrial contractions was prolonged, when the potassium free medium contained thiamine tetra-hydrofurfuryldisulfide (TTFD). Dimethialium propyldisulfide (DMPD) showed the similar effect, while thiamine or thiamine pyrophosphate (TPP) did scarcely. Potassium content in the atria kept in a potassium free medium reduced, but the reduction was prevented by the presence of TTFD contained in the medium. DMPD, thiamine, or TPP could hardly show the similar effect. TTFD is a derivative of thiamine and has a disulfide form in its chemical structure. These specialities were assumed to bring about the above two kinds of effects of TTFD.

Effects of orally administered thiamine tetrahydrofurfuryl disulfide on foetal development of rabbits and monkeys.

In vitro studies with thiamine tetrahydrofurfuryl disulfide (TTFD) revealed that treatment of the fertilized sea urchin ova produced arrest of cellular division at the metaphase stage (1). It was postulated that this was probably due to interference with interconversion of thiol disulfide responsible for the mitotic mechanism (1, 2). The depressant effect of TTFD on cellular proliferation has also been demonstrated in primary monolayer culture of chick heart cells, hamster and monkey kidney cells (3) and amnion (4) and kidney cells of the human embryo (5).

Effects of Orally Administered Thiamine Tetrahydrofurfuryl Disulfide on Foetal Development of Rabbits and Monkeys

In vitro studies with thiamine tetrahydrofurfuryl disulfide (TTFD) revealed that treatment of the fertilized sea urchin ova produced arrest of cellular division at the metaphase stage (1). It was postulated that this was probably due to interference with interconversion of thiol disulfide responsible for the mitotic mechanism (1, 2). The depressant effect of TTFD on cellular proliferation has also been demonstrated in primary monolayer culture of chick heart cells, hamster and monkey kidney cells (3) and amnion (4) and kidney cells of the human embryo (5).