Can thiamine pyrophosphate prevent desflurane induced hepatotoxicity in rats?

PURPOSE: To investigate the effects of thiamine pyrophosphate (TPP) against desflurane induced hepatotoxicity. METHODS: Thirty experimental animals were divided into groups as healthy (HG), desflurane control (DCG) , TPP and desflurane group (TDG). 20 mg/kg TPP was injected to intraperitoneally TDG. After one hour of TPP administration, desflurane was applied for two hours. After 24 hours, liver tissues of the animals killed with decapitation were removed. The oxidant/antioxidant levels and ALT, AST and LDH activities were measured. The histopathological examinations were performed in the liver tissues for all rats. RESULTS: Notwithstanding the levels of oxidants and liver enzymes were significantly increased (p<0.0001), antioxidant levels were significantly decreased in DCG (p<0.0001). On contrary to the antioxidant parameters were increased (p<0.05) the oxidant parameters and liver enzymes were decreased in TDG (p<0.0001). Whereas multiple prominent, congestion, hemorrhage and dilatation were observed in sinusoids and lymphocyte-rich inflammation results in the centrilobular and portal areas of liver tissue in DCG, these findings were observed less frequently in TDG. CONCLUSION : Thiamine pyrophosphate prevented liver oxidative damage induced with desflurane and may be useful in prophylaxis of desflurane induced hepatotoxicity.

Can thiamine pyrophosphate prevent desflurane induced hepatotoxicity in rats?

ABSTRACT PURPOSE : To investigate the effects of thiamine pyrophosphate (TPP) against desflurane induced hepatotoxicity. METHODS : Thirty experimental animals were divided into groups as healthy (HG), desflurane control (DCG) , TPP and desflurane group (TDG). 20 mg/kg TPP was injected to intraperitoneally TDG. After one hour of TPP administration, desflurane was applied for two hours. After 24 hours, liver tissues of the animals killed with decapitation were removed. The oxidant/antioxidant levels and ALT, AST and LDH activities were measured. The histopathological examinations were performed in the liver tissues for all rats. RESULTS : Notwithstanding the levels of oxidants and liver enzymes were significantly increased (p<0.0001), antioxidant levels were significantly decreased in DCG (p<0.0001). On contrary to the antioxidant parameters were increased (p<0.05) the oxidant parameters and liver enzymes were decreased in TDG (p<0.0001). Whereas multiple prominent, congestion, hemorrhage and dilatation were observed in sinusoids and lymphocyte-rich inflammation results in the centrilobular and portal areas of liver tissue in DCG, these findings were observed less frequently in TDG. CONCLUSİON : Thiamine pyrophosphate prevented liver oxidative damage induced with desflurane and may be useful in prophylaxis of desflurane induced hepatotoxicity.

Eficacia del pirofosfato de tiamina o cocarboxilasa en el rescate del pie diabético / Efficacy of thiamine pyrophosphate or carboxylase in the salvage of diabetic foot

El pie diabético representa una de las complicaciones más comunes en pacientes que han tenido una larga evolución. La etiología se circunscribe a la neuropatía, infecciones e isquemia, que actuando en conjunto contribuyen a la secuencia de necrosis tisular, ulceración y gangrena. Lo difícil que resulta su tratamiento hace necesaria la búsqueda de opciones que colaboren en la resolución de esta problemática, que se centra en la hiperglucemia crónica como detonante. El pirofosfato de tiamina o cocarboxilasa realiza múltiples actividades metabólicas y no metabólicas que han sido consideradas importantes en la solución de las alteraciones del diabético por lo que en el presente trabajo se muestran los resultados al emplearlo en pacientes con pie diabético. En un período comprendido entre Enero de 1998 y Julio de 2012 se trataron 29 pacientes con pie diabético: 19 Wagner tipo III y 12 Wagner tipo IV. El manejo consistió en administrar antibióticos, procedimientos quirúrgicos parciales y pirofosfato de tiamina. Se logró el control del proceso infeccioso, la aparición de tejido de granulación y cicatrización de la lesión en un período comprendido entre 2 y 6 meses de acuerdo a la gravedad del problema. Por los datos clínicos y la evolución de los pacientes, se concluye que la administración del pirofosfato de tiamina permitió el control de las disfunciones metabólicas y no metabólicas que conducen a las complicaciones del diabético, por lo que se debe considerar una herramienta para el tratamiento de los diabéticos en general y para el rescate del pie diabético en particular.

Diabetic foot represents one of the most common complications in patients with a long standing disease. The etiology is neuropathy, infections and ischemia that together contribute to the sequence of tissue necrosis, ulceration and gangrene. Since treatment is very difficult, we must look for several options to solve these problems caused by chronic hyperglycemia. Thiamine pyrophosphate or carboxylase perform multiple metabolic and non-metabolic activities that are considered important in the resolution of diabetic impairments, therefore, this work shows the results when using it in patients with diabetic foot. 29 patients with diabetic foot were treated between January 1998 and July 2012: 19 Wagner type III and 12 Wagner type IV. Management was the administration of antibiotics, partial surgical procedures and thiamine pyrophosphate. The infectious process was controlled, the appearance of granulation tissue and scarring of the lesion in a period of 2 to 6 months depending on the severity of the problem. Given the clinical data and evolution of the patients, we conclude that the administration of thiamine pyrophosphate was able to control metabolic and non-metabolic dysfunctions that lead to complications in diabetic patients, therefore we must consider it a tool in the treatment of diabetic patients in general and for diabetic foot salvage in particular.

Thiamine deficiency and cardiac dysfunction in Cambodian infants.

OBJECTIVES: To compare blood thiamine concentrations, echocardiography findings, and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in infants with clinically diagnosed beriberi and healthy matched controls, and to evaluate changes after thiamine treatment. STUDY DESIGN: Sixty-two Cambodian infants (20 cases and 42 controls), aged 2-47 weeks, were enrolled in this prospective study. Echocardiography and phlebotomy were performed at baseline and after thiamine treatment. RESULTS: Both cases and controls were thiamine-deficient, with median blood thiamine diphosphate (TDP) concentrations of 47.6 and 55.1 nmol/L, respectively (P = .23). All subjects had normal left ventricular ejection fraction. The median NT-proBNP concentration in cases (340 pg/mL [40.1 pmol/L]) was higher than previously reported normal ranges, but not statistically significantly different from that in controls (175 pg/mL [20.7 pmol/L]) (P = .10), and was not correlated with TDP concentration (P = .13). Two cases with the lowest baseline TDP concentrations (24 and 21 nmol/L) had right ventricular enlargement and elevated NT-proBNP levels that improved dramatically by 48 hours after thiamine administration. CONCLUSION: Only a minority of thiamine-deficient Cambodian infants demonstrate abnormal echocardiography findings. Thiamine deficiency produces echocardiographic evidence of right ventricular dysfunction, but this evidence is not apparent until deficiency is severe. NT-proBNP concentrations are mildly elevated in sick infants with normal echocardiography findings, indicating possible physiological changes not yet associated with echocardiographic abnormalities.

[Efficacy of thiamine pyrophosphate or carboxylase in the salvage of diabetic foot]. / Eficacia del pirofosfato de tiamina o cocarboxilasa en el rescate del pie diabético.

Diabetic foot represents one of the most common complications in patients with a long standing disease. The etiology is neuropathy, infections and ischemia that together contribute to the sequence of tissue necrosis, ulceration and gangrene. Since treatment is very difficult, we must look for several options to solve these problems caused by chronic hyperglycemia. Thiamine pyrophosphate or carboxylase perform multiple metabolic and non-metabolic activities that are considered important in the resolution of diabetic impairments, therefore, this work shows the results when using it in patients with diabetic foot. 29 patients with diabetic foot were treated between January 1998 and July 2012: 19 Wagner type III and 12 Wagner type IV. Management was the administration of antibiotics, partial surgical procedures and thiamine pyrophosphate. The infectious process was controlled, the appearance of granulation tissue and scarring of the lesion in a period of 2 to 6 months depending on the severity of the problem. Given the clinical data and evolution of the patients, we conclude that the administration of thiamine pyrophosphate was able to control metabolic and non-metabolic dysfunctions that lead to complications in diabetic patients, therefore we must consider it a tool in the treatment of diabetic patients in general and for diabetic foot salvage in particular.

Early metabolic reactivation versus antioxidant therapy after a traumatic spinal cord injury in adult rats.

Disability after traumatic spinal cord injury (TSCI) results from physical trauma and from "secondary mechanisms of injury" such as low metabolic energy levels, oxidative damage and lipid peroxidation. In order to prove if early metabolic reactivation is a better therapeutic option than antioxidant therapy in the acute phase of TSCI, spinal cord contusions were performed in adult rats using a well-characterized weight drop technique at thoracic 9 level. After TSCI, pyrophosphate of thiamine or non-degradable cocarboxylase (NDC) enzyme was used to maintain energy levels, antioxidants such as superoxide dismutase and catalase (ANT) were used to decrease oxidative damage and methylprednisolone (MP), which has both therapeutic properties, was used as a control. Rats were divided into one sham group and six with TSCI; one of them received no treatment, and the rest were treated with NDC, MP, NDC + MP, NDC + ANT or ANT. The ANT group decreased lactate and creatine phosphokinase levels and increased the amount of preserved tissue (morphometric analysis) as well as functional recovery (Basso, Beattie and Bresnahan or BBB motor scale). In contrast, NDC treatment increased lipid peroxidation, measured through thiobarbituric acid reactive substances (TBARS) levels, as well as spinal cord tissue destruction and functional deficit. Early metabolic reactivation after a TSCI may be deleterious, while natural early metabolic inhibition may not be a "secondary mechanism of injury" but a "secondary neuroprotective response". While increased antioxidant defence after a TSCI may currently be an ideal therapeutic strategy, the usefulness of metabolic reactivation should be tested in the sub-acute or chronic phases of TSCI and new strategies must continue to be tested for the early ones.

Actividad de la glucosa-6-fosfato deshidrogenasa en pacientes diabéticos tratados con pirofosfato de tiamina o cocarboxilasa / Activity of clucose-6-phosphate dehydrogenase on diabetic patients treated with thiramine pyrophosphate or cocarboxilase

Trabajos realizados con anterioridad tanto a nivel clínico como experimental en el Instituto de Investigaciones Cientificas Hans Selye, permiten proponer que la cocarboxilasa o pirofosfato de tiamina (PPT) estable en solución, al aplicarse a pacientes con hiperglucemia, mejora la incorporación de la glucosa a los tejidos. Con base en tales hechos, un posterior estudio pretende analizar si el PPT ejerce acción alguna sobre el ciclo de las pentosas. Para demostrar esto, se estudió la conducta de la glucosa-6-fosfato deshidrogenasa (G-6-PD) en el eritrocitos humanos, toda vez que su actividad se ha encontrado disminuida en los pacientes afectados por diabetes mellitus. Para comprobarlo se seleccionaron 10 pacientes de uno y otro sexo, de 45 a 70 años de edad y con diagnóstico de diabetes tipo II. De cada uno se tomó una muestra sanguínea antes de iniciar el traqtamiento con PPT y posteriormente a los 15, 30, 60, 90 y 120 días después de obtener la primera muestra, a fin de determinar la actividad de G-6-PD, así como las de glucosa, colesterol total, HDL, LDL, triglicériados y hemoglobina glucosilada. Los resultados obtenidos demuestran que la glucemia tiende a registrar niveles normales, alcanzando una recuperación física plena en 70 por ciento de los pacientes; en 100 por ciento de ellos también se normalizaron los niveles de colesterol y de triglicéridos. La hemoglobina glucosilada disminuye considerablemente en relación con los valores registrados antes de iniciar el tratamiento. Con respecto a la actividad de la G-6-PD, los autores observaron que ésta se incrementa, en promedio, de 3 a 5 U/g de hemoglobina en los pacientes hiperglucémicos: el máximo incremento de actividad se registra entre el segundo y tercer mes de tratamiento, lo cual indica que PPT participa en: 1) la incorporación de glucosa al interior de los eritrocitos, toda vez que dicha sustancia disminuye la glucosa sérica: 2) la utilización de la glucosa en el metabolismo de esta célilas, y 3) el ciclo de las pentosas, dado que la actividad de la G-6-PD aumenta en forma considerable.

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

Evaluación preliminar de la cocarboxilasa en la protección del miocardio isquémico / Preliminary evaluation of the cocarboxylase in the protection of schemic myocardium

La cocarboxilasa (CC), conocida también como pirofosfato de tiamina, es una coenzima importante para la síntesis de piruvato deshidrogenasa. La deshidrogenasa pirúvica es la enzima reguladora para el catabolismo del piruvato y posiblemente una enzima clave involucrada en la recuperación del miocardio isquémico. Se desarrolló una solución estable de CC y se agregaron concentraciones diferentes de CC a la solución cardiopléjica para evaluara la efectividad de este compuesto en la proteción del paro cardiaco. Se indujo cardioplejía en 47 corazones aislados de ratas perfundidos en una preparación de trabajo. La solución para el parao del corazón se perfundió a una presión de 40 mmHg y a una temperatura de 28-C durante dos minutos. Los corazones se congelaron al final de la isquemia global o al final de la reprefusión, y se hicieron determinaciones en cada corazón, de los niveles de ATP, fosfato de creatina, y lactato. La capacidad hemodinámica se midió antes y después de la cardioplejía. Una mejoría significativa en los parámetros hemodinámicos y metabólico se observó en los corazones sometidos al paro cardiaco electivo con solución cardiopléjica que contenía CC. Tambíen se encontró una respuesta dependiente de la concentración de CC. Concluimos que la CC seríaa un aditivo efectivo a nuestra solución cardiopléjica. Apoyada por HIH Grant HL-32231