The effect of thiamine and its metabolites on peripheral neuropathic pain induced by cisplatin in rats.

Thiamine pyrophosphate (TPP) is the active metabolite of thiamine. This study aimed to investigate the effects of thiamine and TPP on cisplatin-induced peripheral neuropathic pain (PNP). Male albino Wistar type Rattus norvegicus were divided into six groups (n=6) that received 2 mg/kg cisplatin (CIS), 25 mg/kg thiamine (TM), 2 mg/kg cisplatin+25 mg/kg thiamine (CTM), 25 mg/kg TPP (TPP), 2 mg/kg cisplatin+25 mg/kg TPP (CTPP), or distilled water (healthy group; HG) for 8 days intraperitoneally. Analgesic effect was measured with a Basile Algesimeter. IL-1ß, malondialdehyde (MDA), total glutathione (tGSH), thiamine, and TPP were determined in blood samples. Histopathological examinations were performed on removed sciatic nerves. The percent analgesic effects of the CTM and CTPP groups were calculated to be 21.3% and 82.9%, respectively. Increased production of IL-1ß and MDA by cisplatin was inhibited by TPP, while it was not inhibited by thiamine. Conversion of thiamine to TPP significantly decreased in the CIS group. Histopathological and biochemical investigations demonstrated that hyperalgesia and sciatic nerve damage developed in the CIS and CTM groups with low TPP levels. These results indicate that cisplatin inhibits the formation of TPP from thiamine, leading to severe PNP. This finding suggests that TPP may be more beneficial than thiamine for the treatment of cisplatin-induced PNP.

Biochemical and Histological Effects of Thiamine Pyrophosphate against Acetaminophen-Induced Hepatotoxicity.

The aim of this study was to investigate whether thiamine pyrophosphate (TPP) has biochemical and histological preventive effects on oxidative liver damage induced by paracetamol (APAP). Rats were divided into the following groups: healthy control (HG), APAP (AG, 1500 mg/kg, orally), thiamine pyrophosphate (TPPG, 100 mg/kg, intraperitoneally), APAP+NAC (ANAC, 100 mg/kg, intraperitoneally), APAP+TPP (ATPG) and APAP+NAC+TPP (ANTG). Oxidant, antioxidant parameters, liver function tests and histological assessment were performed between groups. Malondialdehyde levels in the AG, HG, TPPG, ANAC, ATPG and ANTG groups were 0.470 ± 0.210, 0.213 ± 0.004, 0.194 ± 0.001, 0.197 ± 0.06, 0.199 ± 0.008 and 0.173 ± 0.010 µmol/g protein, respectively. Total glutathione levels were 7.787 ± 0.395, 14.925 ± 0.932, 13.200 ± 0.984, 13.162 ± 0.486, 13.287 ± 0.787 and 13.500 ± 0.891 µm/g protein, respectively. In the AG group, marked liver damage occurred with the elevation of liver function tests and oxidative stress markers, such as malondialdehyde, myeloperoxidase and nitric oxide (p < 0.05). Biochemical results were congruent with the histological changes of oxidative damage. Compared to the AG group (p < 0.05), TPP significantly reduced oxidant parameter levels in the ATPG group and simultaneously increased the antioxidant parameter levels of catalase and glutathione. The histological changes were improved to almost normal hepatic structure. Moreover, TPP had nearly the same hepatoprotective effect as NAC, and there was statistically no additional benefit with NAC co-treatment. There was no statistically significant difference (p > 0.05) among the ANAC, ANTG and ATPG groups in terms of oxidant/antioxidant levels. TPP proved to be as efficacious as standard therapy and may be beneficial in APAP-induced hepatotoxicity.

El pirofosfato de tiamina reduce el daño celular inducido por hipoxia en el cerebro de ratas neonatas / Thiamine pyrophosphate reduces hypoxia-induced cellular damage in neonatal rat brain

La encefalopatía por hipoxia es causa de discapacidad y requiere de nuevas estrategias terapéuticas. El pirofosfato de tiamina (PPT) es un cofactor esencial de enzimas fundamentales en el metabolismo de la glucosa, cuya disminución puede conducir a la falla en la síntesis de ATP y a la muerte celular. El objetivo de este estudio fue determinar si la administración de PPT, puede reducir el daño celular en un modelo de hipoxia neonatal en ratas. Animales de 11 días de edad fueron tratados con PPT (130 mg/kg) en dosis única o solución salina, una hora antes del protocolo de hipoxia o al término de ésta. Los cerebros fueron colectados para la evaluación del daño celular. Además, se tomaron muestras sanguíneas para evaluar los indicadores gasométricos de presión de dióxido de carbono (PaCO2) y de oxígeno (PaO2) en sangre arterial y pH. Los resultados muestran que la administración de PPT previa a la inducción de hipoxia, reduce el daño celular y restablece los indicadores gasométricos. Estos datos indican que el uso de PPT reduce el daño inducido por la hipoxia en animales neonatos.

Hypoxic encephalopathy is a leading cause of disability and requires new therapeutic strategies. Thiamine pyrophosphate (TPP) is an essential cofactor of fundamental enzymes involved in glucose metabolism. TPP reduction may lead to ATP synthesis failure and cell death. The objective of this study was to determine if TPP administration can reduce cellular damage in a model of neonatal hypoxia in rats. Eleven day old animals were treated with TPP (130 mg/kg) as a single dose or with saline solution one hour before the hypoxia protocol or after ending the protocol. The brains were collected to evaluate cellular damage. Blood samples were also collected to evaluate arterial oxygen tension (PaO2), carbon dioxide tension (PaCO2) and acidity (pH). The results showed that TPP administration previous to hypoxia induction reduces cellular damage and reestablishes arterial blood gases. These data indicate that TPP use reduces the damage induced by hypoxia in neonatal animals.

An investigation of the effect of thiamine pyrophosphate on cisplatin-induced oxidative stress and DNA damage in rat brain tissue compared with thiamine: thiamine and thiamine pyrophosphate effects on cisplatin neurotoxicity.

This study investigated the effects of thiamine pyrophosphate (TPP) at dosages of 10 and 20 mg/kg on oxidative stress induced in rat brain tissue with cisplatin and compared this with thiamine. Cisplatin neurotoxicity represents one of the main restrictions on the drug being given in effective doses. Oxidative stress is considered responsible for cisplatin toxicity. Our results showed that cisplatin increased the levels of oxidant parameters such as lipid peroxidation (thio barbituric acid reactive substance (TBARS)) and myeloperoxidase (MPO) in brain tissue and suppressed the effects of antioxidants such as total glutathione (GSH) and superoxide dismutase (SOD). TPP, especially at a dosage of 20 mg/kg, significantly reduced TBARS and MPO levels that increase with cisplatin administration compared with the thiamine group, while TPP significantly increases GSH and SOD levels. In addition, the level of 8-Gua (guanine), a product of DNA damage, was 1.7 ± 0.12 8-hydroxyl guanine (8-OH Gua)/105 Gua in brain tissue in the control group receiving cisplatin, compared with 0.97 ± 0.03 8-OH Gua/105 Gua in the thiamine pyrophosphate (20 mg/kg) group and 1.55 ± 0.11 8-OH Gua/105 Gua in the thiamine (20 mg/kg) group. These results show that thiamine pyrophosphate significantly prevents oxidative damage induced by cisplatin in brain tissue, while the protective effect of thiamine is insignificant.

Chronic administration of thiamine pyrophosphate decreases age-related histological atrophic testicular changes and improves sexual behavior in male Wistar rats.

Aging is a multifactorial universal process and constitutes the most important risk factor for chronic-degenerative diseases. Although it is a natural process, pathological aging arises when these changes occur quickly and the body is not able to adapt. This is often associated with the generation of reactive oxygen species (ROS), inflammation, and a decrease in the endogenous antioxidant systems, constituting a physiopathological state commonly found in chronic-degenerative diseases. At the testicular level, aging is associated with tissue atrophy, decreased steroidogenesis and spermatogenesis, and sexual behavior disorders. This situation, in addition to the elevated generation of ROS in the testicular steroidogenesis, provides a critical cellular environment causing oxidative damage at diverse cellular levels. To assess the effects of a reduction in the levels of ROS, thiamine pyrophosphate (TPP) was chronically administered in senile Wistar rats. TPP causes an activation of intermediate metabolism routes, enhancing cellular respiration and decreasing the generation of ROS. Our results show an overall decrease of atrophic histological changes linked to aging, with higher levels of serum testosterone, sexual activity, and an increase in the levels of endogenous antioxidant enzymes in TPP-treated animals. These results suggest that TPP chronic administration decreases the progression of age-related atrophic changes by improving the intermediate metabolism, and by increasing the levels of antioxidant enzymes.

The effect of thiamine and thiamine pyrophosphate on oxidative liver damage induced in rats with cisplatin.

The aim of this study was to investigate the effect of thiamine and thiamine pyrophosphate (TPP) on oxidative stress induced with cisplatin in liver tissue. Rats were divided into four groups; thiamine group (TG), TPP + cisplatin group (TPG), healthy animal group (HG), and cisplatin only group (CG). Oxidant and antioxidant parameters in liver tissue and AST, ALT, and LDH levels in rat sera were measured in all groups. Malondialdehyde levels in the CG, TG, TPG, and HG groups were 11 ± 1.4, 9 ± 0.5, 3 ± 0.5, and 2.2 ± 0.48 µ mol/g protein, respectively. Total glutathione levels were 2 ± 0.7, 2.8 ± 0.4, 7 ± 0.8, and 9 ± 0.6 nmol/g protein, respectively. Levels of 8-OH/Gua, a product of DNA damage, were 2.7 ± 0.4 pmol/L, 2.5 ± 0.5, 1.1 ± 0.3, and 0.9 ± 0.3 pmol/L, respectively. A statistically significant difference was determined in oxidant/antioxidant parameters and AST, ALT, and LDH levels between the TPG and CG groups (P < 0.05). No significant difference was determined between the TG and CG groups (P > 0.05). In conclusion, cisplatin causes oxidative damage in liver tissue. TPP seems to have a preventive effect on oxidative stress in the liver caused by cisplatin.

A comparative investigation of biochemical and histopathological effects of thiamine and thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat ovarian tissue.

In this study, the biochemical and histopathological effects of thiamine and thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat ovarian tissue were investigated. Animals were divided into four groups of six rat each, ovarian ischemia-reperfusion (IR), 25 mg/kg thiamine + ovarian ischemia-reperfusion (TIR), 25 mg/kg thiamine pyrophosphate + ovarian ischemia-reperfusion (TPIR) and Sham group (SG). The results of the biochemical experiments have shown that the rat ovarian tissue with thiamine treatment, the level of MDA, GSH and the 8-hydroxyguanine are almost the same as the IR group; while in the group with thiamine pyrophosphate treatment, the level of MDA, GSH and the 8-hydroxyguanine are almost the same as the SG. Ovarian tissue of rats in the IR group were congested and dilated vessels, edema, hemorrhage, necrotic and apoptotic cells. In this group, the migration and the adhesion of the polymorphonuclear leucocytes to the endothelium were observed. Both ovaries in TPIR group, there was no difference according to the SG. Histopathology of ovarian tissues in the TIR group was almost the same with the IR group. Our results indicate that thiamine pyrophosphate significantly prevents the ischemia-reperfusion induced oxidative damage in ovarian tissue, whereas thiamine has no effect. In conclusion, we have found that thiamine pyrophosphate prevents oxidative damage due to ischemia-reperfusion injury, whereas thiamine does not have this effect. Furthermore, we have confirmed that the results of our biochemical analyses are in concordance with the histopathological findings.

DNA-loaded chitosan oligosaccharide nanoparticles with enhanced permeability across Calu-3 cells.

Chitosan oligosaccharide (oligoCS) is a low molecular weight chitosan and its potential for DNA delivery is described here. DNA-loaded oligoCS nanoparticles were prepared by ionic gelation using thiamine pyrophosphate (TPP) as cross-linker. The nanoparticles with oligoCS:DNA: TPP weight ratio of 50:1:25 were approximately 170 nm in diameter with a zeta potential of +40 mV, and were used in the permeability study. The cytotoxicity of oligoCS solutions and nanoparticles was evaluated by MTT assay. The concentrations that exhibited minimal cytotoxicity were employed to investigate their effect on trans-epithelial electrical resistance (TEER) and cellular uptake across the Calu-3 cell layer which was used as a nasal epithelial model. OligoCS nanoparticles were able to cause a significant and reversible decrease in TEER and promote efficient cellular uptake. In addition, the oligoCS nanoparticles were able to enhance paracellular permeability to a greater extent than oligoCS solutions at an equivalent concentration. However, the oligoCS nanoparticles were too large to cross the cell layers through the paracellular route. The transcellular pathway appeared to be the major mechanism of the transportation of oligoCS nanoparticles across the cell layers. OligoCS nanoparticles also allowed efficient DNA incorporation, thereby providing the possibility of controlled nucleic acids release and absorption across epithelial surface.

Thiamine supplementation in the critically ill.

PURPOSE OF REVIEW: To summarize the properties of thiamine and evaluate current evidence on thiamine status and supplementation, for different populations of critically ill patients. RECENT FINDINGS: Thiamine, in the form of thiamine pyrophosphate, is a critical co-factor in the glyocolysis and oxidative decarboxylation of carbohydrates for energy production. Different studies have shown that critical illness in adults and children is characterized by absolute or relative thiamine depletion, which is associated with an almost 50% increase in mortality. Thiamine deficiency should be suspected in different clinical scenarios such as severe sepsis, burns, unexplained heart failure or lactic acidosis, neurological disorder in patients with previous history of alcoholism, starvation, chronic malnutrition, long-term parenteral feeding, hyperemesis gravidarum, or bariatric surgery. Nonetheless, thiamine supplements are not routinely given to critically ill patients. Clinicians should be able to suspect and recognize risk factors for the occurrence of severe neurological disorders secondary to thiamine deficiency, as early treatment can prevent the appearance of permanent neurological damage. SUMMARY: Symptoms and signs associated with thiamine deficiency lack sensitivity and specificity in critically ill patients. Consequently, depletion is frequently unrecognized and underdiagnosed by clinicians. Potentially deleterious consequences of thiamine depletion should be avoided by early and appropriate supplementation.

Effect of thiamine pyrophosphate on levels of serum lactate, maximum oxygen consumption and heart rate in athletes performing aerobic activity.

The aim of this study was to determine the effect of thiamine pyrophosphate (TPP) on serum lactate levels, maximum oxygen consumption (Vo(2max)) and heart rate in male athletes performing aerobic activity. A double-blind, randomized, crossover study was performed in which lactate levels, Vo(2max) and heart rates in 27 male athletes were compared at rest and after exercise, following administration of placebo (sodium chloride 0.9%) or TPP (1 mg/kg). At rest, serum lactate levels after placebo or TPP were similar; however, after exercise, the levels were lower in the athletes after taking TPP than after placebo. During exercise, Vo(2max) in athletes on TPP was higher than on placebo. At rest, heart rate after taking placebo or TPP was similar but, after exercise, heart rate was lower after taking TPP than after placebo. It is concluded that TPP caused serum lactate levels and heart rate to be lower than placebo and Vo(2max) to be higher in athletes performing aerobic physical activity.

Chitosan-thiamine pyrophosphate as a novel carrier for siRNA delivery.

PURPOSE: A novel siRNA carrier was formulated between chitosan (CS) and thiamine pyrophosphate (TPP). Their ability to deliver siRNA were evaluated in stable and constitutive EGFP-expressing HepG2 cells. METHODS: CS-TPP was prepared by dissolving CS in TPP solution at a CS:TPP molar ratio of 1.5:1. Complexes of CS-TPP/siRNA were formed at varying weight ratios and characterized using gel electrophoresis. Their morphologies and particle sizes were evaluated, and the transfection efficiency and cytotoxicity of CS-TPP/siRNA complexes were examined in stable and constitutive EGFP-expressing HepG2 cells. RESULTS: Gel electrophoresis results indicated that binding of CS-TPP and siRNA depended on the molecular weight (MW) and weight ratio of CS, and the particle sizes of CS-TPP/siRNA complexes were in nano-size. The CS-TPP-mediated siRNA silencing of the endogenous EGFP gene occurred maximally with 70-73% efficiency. The CS-TPP/siRNA complex with the lowest MW of CS (20 kDa) at a weight ratio of 80 showed the strongest inhibition of gene expression, which was higher than Lipofectamine 2000. Over 90% the average cell viabilities of the complexes were observed by MTT assay. CONCLUSIONS: This study suggests that CS-TPP is straightforward to prepare, safe and exhibits significantly improved siRNA delivery potential in vitro.

[The effect of cocarboxylase treatment on erythrocyte transketolase and blood thiamine in patients with end stage renal disease undergoing maintenance hemodialysis]. / Wplyw leczenia kokarboksylaza na aktywnosc transketolazy w erytrocytach i stezenie tiaminy we krwi u chorych ze schylkowa niewydolnoscia nerek, leczonych powtarzana hemodializa.

The depressed ETKA in ESRD patients is supposed to be caused and/or aggravated by several factors among which the diminished content of thiamine in blood and/or disturbances of thiamine utilization seem to play the major role. This role stems from the fact that thiamine acts as the cofactor of transketolase. In order to check the therapeutic significance of this relationship we introduced the thiamine pyrophosphoric acid ester chloride (Cocarboxylasum-CC) administration in 25 patients (mHD + CC). Immediately after each HD performance CC was given i.v. during 12 weeks in a doses of 5 mg/kg b.w., 3 times a week. The blood for ETKA value, free and total thiamine in plasma and erythrocytes, as well as, the total protein and albumins/globulins index investigation was drawn before, after 6 and 12 weeks of CC administration, and 3 months after cessation of this therapy. In 10 patients, on maintenance HD nontreated by CC (mHD), the blood was drawn at the same time intervals. Normal values we obtained from 15 healthy volunteers. For ETKA evaluation photocolorimetric method was used, thiamine content in blood was estimated by fluorimetric method. At the beginning of the study the mean value of ETKA, in two examined groups, was found statistically decreased (p < 0.01) when compared with normals. Mean values of thiamine in plasma and erythrocytes were lower but did not differ significantly from those in normals. After 6 weeks of CC administration ETKA value increased, but only after 12 weeks it increased significantly (p < 0.01), reaching normal value. On the other hand, striking increase in plasma thiamine and erythrocyte thiamine levels was observed after 6 weeks of CC administration already (p < 0.01). Three months after cessation of CC administration significant decrease in ETKA value and thiamine level in blood was observed (p < 0.01). ETKA returned to lower value than in normals even in the presence of still high thiamine levels in blood. In mHD patients nontreated by CC the ETKA value and thiamine levels in blood did not change significantly during all periods of study. The nutritional status assessed by total protein and albumins/globulins index did not change in both groups through the study. We conclude, the administration of high doses of CC to ESRD patients on maintenance hemodialysis HD was successful in terms of increasing ETKA value and thiamine levels in blood without any side effects. Thus, supplementation with large doses of CC deserves further study because it promises to be another adjunct in the treatment of potential thiamine deficiency and metabolic disturbances in the course of dialysotherapy.

Treatment of mitochondrial encephalomyopathy with a combination of cytochrome C and vitamins B1 and B2.

The therapeutic efficacy of a regimen consisting of intravenous injection of Cardiocrome, containing cytochrome c, flavin mononucleotide and thiamine diphosphate for mitochondrial encephalomyopathy (MEM) was examined. This combined therapy was applied to nine patients with MEM, including four with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. For the standard regimen, Cardiocrome was first injected daily, usually for 4 weeks, and later by means of intermittent injections for maintenance treatment. Clinical improvement was obtained in eight of the patients. Improvement was observed in the muscle symptoms of easy fatigability, motor disability and severity of stroke-like episodes, as well as in various other symptoms such as phosphate, tinnitus, headache, corneal edema, chilblains, thalamic pain, respiratory failure, and nystagmus. This clinical improvement was maintained for more than 1 year by additional intermittent injections. In conclusion, this therapy was fairly effective for the management of patients with MEM.

Long-term therapy with cytochrome c, flavin mononucleotide and thiamine diphosphate for a patient with Kearns-Sayre syndrome.

Cardiocrome, containing cytochrome c, flavin mononucleotide and thiamine diphosphate, was administered intravenously for 22 months to a patient with Kearns-Sayre syndrome. This combined therapy alleviated the patient's easy fatigability, motor disability, corneal edema and chilblains, but was not effective for his ophthalmoplegia, blepharoptosis or hearing loss. Truncal ataxia, dysphagia and an atrioventricular block appeared even with this therapy. Although the abnormal distribution of cerebral blood flow demonstrated by single photon emission computed tomography was improved, serial cranial magnetic resonance imaging and electrophysiological examination revealed progressive changes. In conclusion, this therapy was favorably effective for impaired skeletal muscle function and corneal edema, but not for ocular movements, central nervous system symptoms or cardiac conduction abnormalities, because irreversible degeneration had probably occurred in these organs.

[Prediction of the effects of energy-stabilizing drugs in diabetes mellitus]. / Prognozirovanie deistviia énergostabiliziruiushchikh preparatov pri sakharnom diabete.

The authors describe a method for the prediction of the therapeutic effect of energy-stabilizing drugs, that helps rapidly select the optimal individual therapeutic policy. The method is based on measurement of the red cell ATP concentration in the course of in vitro incubation of cells in polyionic medium with the drug, and may be used in various diseases associated with energy metabolism disorders on the cellular level. The authors have used this method for the selection of a thiamine drug to be included in therapy of a diabetic in the period of the disease compensation.

Kinetics of thiamin and thiamin phosphate esters in human blood, plasma and urine after 50 mg intravenously or orally.

The concentrations of thiamin and thiamin monophosphate and diphosphate in plasma and whole blood samples were assessed in six healthy subjects for 12 h and in urine for 24 h following an IV and PO bolus dose of 50 mg thiamin HCl. Unphosphorylated thiamin increased rapidly in plasma after IV administration and then decreased to its initial value within 12 h in all but one subject; the half-life was 96 min. Thiamin mono and -diphosphate increased moderately (56%), and decreased slowly; the half-life of diphosphate was 664 min. Within 24 h, 53% of the administered dose was recovered in the urine, indicating a restricted distribution. After oral administration, the peak thiamin concentration in plasma was reached after 53 min and the concentration then had increased to 179% of its initial value. The elimination half-life was 154 min, and only 2.5% of the given dose was recovered in the urine. The relative bioavailability of thiamin was 5.3%. A moderate amount of the administered thiamin was stored in blood. Other body tissues must play an important part, therefore, in the distribution of thiamin.

[Acid-base equilibrium and blood gases in pregnant women with habitual abortion after metabolic therapy]. / Kislotno-osnovnoe sostoianie i gazy krovi u beremennykh s privychnym nevynashivaniem na fone metabolicheskoi terapii.

Blood oxygen transport, pH, acid-base status, urinary ketone level and urobilinogen were studied in 52 pregnant women in whom pregnancy ran a normal course and in 56 ones with a history of habitual abortions, treated for metabolic disorders. Signs of metabolic acidosis in the presence of respiratory alkalosis at the expense of pulmonary hyperventilation were detected in women with normal pregnancy. Follow-up of acid-base status and gases of blood, aciduria and ketonuria in pregnant women with a history of habitual abortions has revealed in them respiratory alkalosis signs presenting in hypoxemia and reduced oxygen saturation and ketonuria. Metabolic therapy included in combined therapeutic schemes for such patients actively influenced the processes of metabolic acidosis and ketonuria compensation, probably at the expense of its normalizing effect on intracellular metabolism. Metabolic therapy of pregnant women liable to spontaneous abortions, due to ovarian hypofunction had a marked antihypoxic effect, normalized the bicarbonate system status and was therefore conducive to improvement of oxygen transport to maternal tissues and the fetus.

Utilidad del pirofosfato de tiamina (cocarboxilasa) estable en solución en dos casos posinfarto del miocardio / Usefulnes of solution-stable tiamyne pyrophosphate (cocarboxylase) on two cases of postmyocardial infarction

En este estudio clínico se analizó el papel central que desempeña la cocarboxilasa (pirofosfato de tiamina) en el metabolismo energético celular, en particular en el tejido miocárdico, cuya dependencia de la energía es absolutamente constante. Se estudiaron dos casos de posinfarto agudo del miocardio, en los cuales la zona de necrosis desapareció después del tratamiento con cocarboxilasa con sus enlaces de fosfato estables en solución fisiológica. En uno de estos pacientes se mostró lisis completa de un trombo

Pirofosfato de tiamina como terapia preventiva y regenerativa delproceso de envejecimiento de los diábeticos / Thiamine pyrophosphate as a preventive and regenerative therapy in the aging of diabetics

Se han postulado diversas teorías sobre el envejecimiento, pero en el trabajo sólo se contempla a la depleción de la energía metabólica como causa inmediata y sustancial de los procesos degenerativos, cuya manifestación más visible es la disminución progresiva de las funciones normales del organismo, que se traduce en la pérdida gradual de la energía de adaptación y finaliza con la muerte. La falla de oxidación completa de la glucosa explica la merma energética sufrida por cualquier organismo aerobio, que exhibe una serie de eventos a nivel molecular, celular y orgánico consecuentes a un bloque del efecto Pasteur ocasionado por el efecto Crabtree. Por tal motivo, se escogió a la diabetes como modelo de envejecimiento prematuro y al pirofosfato de tiamina (PPT) o cocarboxilasa como terapia preventiva y degenerativa

[Effect of thiamine and its metabolites on the activity of tissue and purified alcohol dehydrogenase]. / Vliianie tiamina i ego metabolitov na aktivnost' tkanevoi i ochishchennoi alkogol'degidrogenazy.

Thiamine is shown to have a stimulatory action on ++alcohol dehydrogenase activity in blood and small intestines of white rats. The same effect is obtained on the purified ++alcohol dehydrogenase as well. Thiochrome inhibits the enzyme preparation.