Thiamine Propyl Disulfide Research Articles

Effect of ultraviolet on thiamine and thiamine disulfides

In a neutral medium, the exposure of thiamine disulfide to the ultraviolet of solar radiation (as well as to the ultraviolet radiation of mercury lamp with λ > 300 nm) results in the formation of a thiamine molecule with closed thiazole ring and a molecule of thiamine thiazolone. Asymmetric thiamine disulfides, e.g., thiamine propyl disulfide, on exposure to ultraviolet (UVA range) produced thiamine and propyl disulfides. Thiamine and thiazolone of thiamine are stable upon exposure to light of 320-400 nm (UVA range). UV irradiation within spectral range of 200-300 nm results in further photodestruction of thiamine and thiamine thiazolone and production of 2-methyl-4-amino-5aminomethyl-pyrimidine as the main photoproduct. The possibility to use thiamine disulfide derivatives as a promising class of anti-cataract drugs as well as drugs to decrease the toxic effect of ultraviolet radiation on human retina is discussed.

Human brain activation in response to olfactory stimulation by intravenous administration of odorants

To identify the BOLD effects related to olfaction in humans, we recorded functional magnetic resonance imaging (fMRI) scans in response intravenously instilled thiamine propyl disulfide (TPD) and thiamine tetrahydrofurfuryl disulfide monohydrochloride (TTFD). TPD and TTFD evoked a strong and weak odor sensation, respectively. Since we did not spray the odor stimuli directly, this method is expected to reduce the effect caused by direct stimulation of the trigeminal nerve. For the analysis of fMRI data, statistical parametric mapping (SPM2) was employed and the areas significantly activated during olfactory processing were located. Both strong and weak odorants induced brain activities mainly in the orbitofrontal gyrus (Brodmann's area: BA 11) in the left hemisphere. TPD (a strong odorant) induced activity in the subthalamic nucleus in the left hemisphere and the precentral gyrus (BA 6) and insula in the right hemisphere. TTFD (a weak odorant) induced activity in the superior frontal gyrus (BA 11) in the right hemisphere. In both circumstances, there was an increase in blood flow at the secondary olfactory cortex (SOC) but not the primary olfactory cortex (POC), probably due to a habituation effect in the POC. From the present results, we found brain activity in not only odor-specific regions but also regions whose levels of activity were changed by an intensity difference of odor stimuli.

Neuromagnetic Changes of Brain Rhythm Evoked by Intravenous Olfactory Stimulation in Humans

To identify the changes in the respective frequency band and brain areas related to olfactory perception, we measured magnetoencephalographic (MEG) signals before and after instilling intravenously thiamine propyl disulfide (TPD) and thiamine tetrahydrofurfuryl disulfide monohydrochloride (TTFD), which evoked a strong and weak sensation of odor, respectively. For the frequency analysis of MEG, a beamformer program, synthetic aperture magnetometry (SAM), was employed and event-related desynchronization (ERD) or synchronization (ERS) was statistically determined. Both strong and weak odors induced ERD in (1) beta band (13-30 Hz) in the right precentral gyrus, and the superior and middle frontal gyri in both hemispheres, (2) low gamma band (30-60 Hz) in the left superior frontal gyrus and superior parietal lobule, and the middle frontal gyrus in both hemispheres, and (3) high gamma band 2 (100-200 Hz) in the right inferior frontal gyrus. TPD induced ERD in the left temporal, parietal and occipital lobes, while TTFD induced ERD in the right temporal, parietal and occipital lobes. The results indicate that physiological functions in several regions in the frontal lobe may change and the strength of the odor may play a different role in each hemisphere during olfactory perception in humans.

Synthesis of stable analogues of thiamine di- and triphosphate as tools for probing a new phosphorylation pathway.

Thiamine (vitamin B1) is an essential nutritional factor metabolized inside the body in its mono-, di-, and triphosphate forms. Although the action of thiamine and thiamine diphosphate have been intensely investigated, many questions remain unanswered and the role of thiamine triphosphate is still especially unknown. To probe recent hypotheses on the implication of thiamine triphosphate in a new phosphorylation pathway involving synaptic proteins, we synthesized a series of thiamine di- and triphosphate analogues that are resistant to both enzymatic and chemical hydrolyses. The key step in the preparation of the title compounds is the coupling of thiamine propyl disulfide with adequately protected methylenebis-phosphonic acid, the corresponding triphosphate analogue, and difluoromethylenebisphosphonic acid.

鼻閉の改善が嗅覚に及ぼす影響

In this study, the effects of reductions in nasal obstruction by endonasal surgery on the sense of smell were exarmined by an intravenous olfaction test using thiamine propyl disulfide (TPD). Ten cases of nasal obstruction (5 cases of chronic sinusitis 2 cases of hypertrophic rhinitis and 3 cases of allergic rhinitis) were treated surgically from January,1997 to November,1997. Among 8 cases that became conscious of an improvement in nasal obstruction, duration time was prolonged in 5cases, while latent time was shortened in 7 cases, in the intravenous olfaction test. The findings in this study suggested that the improvement of nasl obstruction by the endonasal surgery involving, the removal of the barrier to the olfactory mucosa, contributed to a reduction in the time required to perceive a smell.

Drug‐induced Chronic Pigmented Purpura

A close correlation between purpuric reaction and drugs was observed in seven cases of chronic pigmented purpura. The patients developed purpuric lesions after taking certain drugs for more than 3 years, were thiamine propyldisulfide in 2 cases, and chlordiazepoxide in 1 case. The purpuric lesions stopped recurring after removal of the drugs in the rest of the cases. It is suggested that drugs are among the etiological factors in chronic pigmented purpura.

Significance of Intravenous Olfaction Test Using Thiamine Propyldisulfide (Alinamin) in Olfactometry

The significance of intravenous olfaction test in olfactometry was studied by injection of thiamine propyldisulfide (Alinamin) intravenously. An original solution of Alinamin is a thiol-type derivative of vitamin B1, and releases a mercaptan smell (garlic smell) in expired air when it arrives at the olfactory epithelium via the nasopharynx. In the intravenous olfaction test (Alinamin test), the latent time which is a period between the initiation of injection and recognition of garlic smell, and duration time which is a period between the recognition and disappearance of smell are measured. Our results indicated that latent time is influenced by olfactory acuity and duration time depends on olfactory adaptation phenomenon. Central olfactory disorders were highly suspected in hyposmia patients with duration time of less than 15 sec, and nonresponders in Alinamin test always showed poor prognosis in the recovery of olfactory acuity. It was considered that the Alinamin test is useful not only for estimating the degree of olfactory disorders, but also for differential diagnosis of impaired lesions and olfactory prognosis.

Altered thiamine propyl disulfide metabolism in rats with liver injury induced by carbon tetrachloride and D-galactosamine.

The urinary excretion of 2-hydroxypropyl methyl sulfone (2HPMS) and methyl propyl sulfone (MPS) after oral administration of thiamine propyl disulfide (TPD) was examined in rats with liver injury induced by carbon tetrachloride (CCl4) and D-galactosamine (GAL), in order to investigate the effect of liver damage on TPD metabolism. In the CCl4-treated rats, excretion of 2HPMS and MPS markedly decreased at an early stage, but MPS thereafter started to be excreted rapidly as compared with the control rats. On the other hand, 2HPMS continued to be excreted in lesser amounts in the CCl4-treated rats in the control rats even after 72h. In the GAL-treated rats, excretion of 2HPMS and MPS did not vary so greatly at a dose of 300 mg/kg, but alteration of excretion of 2HPMS and MPS was clearly observed at a dose of 600 mg/kg and slightly more at a dose of 1200 mg/kg. In comparison with the CCl4-treated rats, delay of MPS excreation was not observed but excretion of 2HPMS more delayed in the GAL-treated rats. Concerning the amount excreted in the 0-72 h urine, decrease in 2HPMS and increase in MPS was the same as the CCl4-treated rats. From light microscopic examination, the liver of rats treated at a dose of 1000 mg/kg of GAL was found to be injured over a long period. Form these results, TPD metabolism was suggested to be impaired in proportion to be severity of liver damage, and decrease of 2HPMS excretion was confirmed in liver-injured rats, as well as the patients with liver disease. Our previous suggestion that measurement of 2HPMS excreted in the urine was a useful test for quantification of liver disease was supported.

Determination of urinary metabolites of thiamine propyl disulfide in humans.

Gas chromatographic procedure for the quantitative determination of methyl propyl sulfone (MPS), 2-hydroxypropyl methyl sulfone (2HPMS) and 3-hydroxypropyl methyl sulfone (3HPMS) in urine was developed. By using this procedure, the urinary excretion of MPS, 2HPMS and 3HPMS after oral dose of thiamine propyl disulfide (TPD) was investigated in healthy adults, in order to assess their ability of drug disposition including metabolism. Among these metabolites, 2HPMS was predominant and the other two were minor. 2HPMS was excreted most in the 24--36 h urine and the time course of excretion of this metabolite was almost the same among these subjects. In 4th day urine, a significant amount of 2HPMS was still excreted. On the contrary, the time course of excretion of MPS varied among subjects and also at different occasions in the same subjects. 3HPMS was excreted most in the 0--12 or 12--24 h urine and more rapidly excreted than 2HPMS. Two-fold interindividual differences in the amount of 2HPMS in the 0--48 h urine occurred and intraindividual difference was also observed. Inter- and intraindividual differences in the amount of MPS in 0--48 h urine were much larger than that in 2HPMS. In 3HPMS, these differences were slightly less than in 2HPMS. Sex difference in the excretion of MPS and 2HPMS was not observed.

Decreased urinary excretion of thiamine propyl disulfide metabolites in patients with liver disease.

The urinary excretion of 2-hydroxypropyl methyl sulfone (2HPMS) and methyl propyl sulfone (MPS) after oral administration of thiamine propyl disulfide (TPD) was examined in the patients with various liver diseases, in order to investigate the relationship between the liver function and the ability of drug disposition including metabolism. The patients were divided into six groups as follows ; acute hepatitis in convalescent stage (AHconv), acute hepatitis in active stage (AHact), chronic inactive hepatitis (CIH), chronic active hepatitis (CAH), liver cirrhosis in compensated stage (LCcom) and decompensated stage (LCdec). The results obtained from these groups were compared with those of normal subjects. For MPS, only LCdec showed either lesser or delayed excretion in the 0-48 h urine compared to normal subjects. In other liver diseases the excretion pattern of MPS was similar with that of normal subjects, and the amount excreted in the 0-48 h urine was not significantly different. In urinary excretion of 2HPMS, the amount excreted in the 0-48 h urine decreased in the order CIH > AHconv > AHact > CAH > LCcom > LCdec, and the decrease in the amount correlated roughly to the severity of liver disease. This amount in liver disease, except CIH, was significantly less than that in normal subjects. Differences between CIH and CAH, and LCcom and LCdec were also significant. Delayed excretion of 2HPMS was observed in chronic liver diseases, especially in LCdec. Excretion of 2HPMS in the 0-48 h urine was correlated with the alterations of liver functions such as serum albumin concentration, serum choline esterase activity, hepaplastin test and indocyanine green tolerance test. From the results, measurement of the amount of 2HPMS excreted in the 0-48 h urine after oral dose of TPD is suggested to be useful for evaluation of the liver function.

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

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.

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.

A study on olfaction of the laryngectomized patients by the artificial airway tube method (author's transl)

The authors noticed the recovery of the nasal air current in the laryngectomized patients by connecting a tube between the tracheal stoma and the naris, so named this technique an artificial airway tube method. In this manner, the olfactory acuities of 60 laryngectomized patients, ranged from 9 days to 18 5/6 years postoperatively, were evaluated by measuring the detection threshold for the smell of various odors such as beta-phenyl ethyl alcohol, cyclotene and iso-valeric acid. At the same time we also measured respectively the onset and duration time for the sense of smell of Alinamin (Thiamine propyl disulfide) administered intravenously. Aside from the methods above mentioned, it is also known that swallowing of air leads a little olfactory sensation by nasal rout in some laryngectomized individuals. Thus utilizing airswallowing, olfactory testings by these 3 odors were undergone to guess their olfaction in daily life. Results obtained are summarized as follows; 1. The mean detection threshold for each of these 3 substances in the laryngectomized patients was nearly equal to that obtained in normal persons. While in the intravenous olfaction tests, more inferior data were seen in the laryngectomized patients than that of normal controls. Namely, not only the time needed for the onset of the sense of smell was twice longer, but also its duration shortened obviously as compared with their normal values.2. The best score was revealed in the subjects within one year after surgery in comparison with the others. 3. No significant differences of the olfactory acuities were observed between the groups, one with esophageal speech and the other with artificial voice apparatus. 4. When the laryngectomized patients put on the artificial airway tube, microclimate in the nasal cavity might be similar to that of normal one. 5. Olfactory sensation by swallowing procedure appeared in 40% of the laryngectomized patients in this series. But, the mean detection thresholds of individual odors were greatly higher than those obtained by the artificial airway tube method. For olfactory sensation, the longer the postoperative period, the more increased the incidence of its appearance.This study showed that the olfaction did not change in these patients. The assumption istherefore made that neurological changes in the terminal endings in this special sense organ do not occur after total laryngectomy.

THIAMINE DERIVATIVES IN SUBACUTE NECROTIZING ENCEPHALOMYELOPATHY

Twenty-one patients in whom the diagnosis of subacute necrotizing encephalomyelopathy (SNE, Leigh's disease) was made, have been treated with large doses of thiamine hydrochloride, thiamine propyldisulfide (TPD) or thiamine tetrafurfuryldisulfide (TTFD). In 12, the diagnosis is secure and in 9 it is presumptive. The incidence and quality of remissions in patients in both categories exceeded those described in the literature in 84 untreated patients with this disease. In general, remissions correlated well with high thiamine levels in the cerebrospinal fluid and exacerbations with the reverse. The ultimate failure of vitamin therapy in several patients who initially did well seemed to correlate with the tendency of CSF thiamine levels to fall during the course of continuous therapy. Preliminary results indicate that substituted thiamine derivatives (TPD and TTFD) were more efficacious in raising CSF thiamine levels than thiamine. TTFD has the further advantage of imparting little odor to treated patients. In the one case in which a comparative study was done, the intravenous route was more effective than the oral one in raising blood and CSF levels but in high dosage therapy raised CSF levels satisfactorily at least in the early days and weeks of treatment of many cases. While thiamine and its derivatives appear to be of benefit, a permanent solution to the therapeutic problem will probably come from another source.

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

The transport mechanism of thiamine propyl disulfide into human blood cell membrane

Thiamine propyl disulfide (TPD), a lipotropic derivative related to thiamine, has a specific ability to cross the biological membrane. In the present paper the mechanism of reduction and uptake of TPD in blood is described. TPD is converted to thiamine by a heat stable factor(s) in blood cells and to a slight extent by plasma. This reducing ability of blood cells is increased with the aid of plasma. From the fact that this conversion is inhibited by p- chloromercuribenzoic acid, it is postulated that SH groups may play a major role in this reduction process. A possible explanation on the mechanism for accumulation of TPD in blood cells is presented.

Subacute necrotizing encephalomyelopathy. Effects of thiamine and thiamine propyl disulfide.

Treatment of a case of Leigh's disease with (1.5 gm) thiamine and thiamine propyl disulfide (300 mg) was associated with marked improvement in weight and neurologic status and appeared to reverse respiratory failure. For reasons yet unknown, it became increasingly difficult to maintain thiamine levels above 50μg/100 ml in the patient's cerebrospinal fluid (CSF), through blood levels exceeded 1,000μg/100 ml. Remissions correlated with increased CSF thiamine concentrations, exacerbations with low levels. Brain tissue obtained at autopsy had only a slightly elevated total thiamine content (2μg/gm). No thiamine triphosphate was present in pons or cerebellum. Initial successes with this case and several others suggest that there may be some rationale for the use of thiamine and thiamine propyl disulfide in this condition.

Thiamine propyl disulfide: absorption and utilization.

Abstract The absorption and utilization of thiamine propyl disulfide, an allithiamine derivative, was compared with that of thiamine hydrochloride, in normal subjects and in alcoholics with and wit...

Thiamine Derivatives of Disulfide Type. XI. Oxidation of Dipropyl Disulfide with Hydrogen Peroxide and Properties of the Products

Investigation was made on the oxidation of dipropyl disulfide with hydrogen peroxide in acetic acid, as a basis for kinetic studies in the synthesis of thiamine propyl disulfide (TPD). Separation and detection methods of the oxidation products by thin-layer chromatography were established. Among these products, thiolsulfinate (PrSSOPr), thiolsulfonate (PrSSO2Pr), sulfinic acid and sulfonic acid were identified. The stability, solubility, IR and UV-spectrum of PrSSOPr and PrSSO2Pr, which react with thiamine to produce TPD, were examined.