RESUMO
BACKGROUND: It is challenging to find an iron compound that combines good bioavailability with minimal sensory changes when added to seasonings or condiments. Ferric pyrophosphate (FePP) is currently used to fortify bouillon cubes, but its bioavailability is generally low. Previously, the addition of a stabilizer, sodium pyrophosphate (NaPP), improved iron bioavailability from a bouillon drink. OBJECTIVE: We assessed whether there is a dose-response effect of added NaPP on iron bioavailability from local meals prepared with intrinsically labeled FePP-fortified bouillon cubes in young Nigerian women using iron stable isotope techniques. METHODS: In a double-blind, randomized, cross-over trial, women (n = 24; aged 18-40 y; mean BMI 20.5 kg/m2) consumed a Nigerian breakfast and lunch for 5 d prepared with bouillon cubes containing 2.5 mg 57Fe (as FePP) and 3 different molar ratios of NaPP: 57Fe (0:1, 3:1, and 6:1). Iron bioavailability was assessed by measuring 57Fe incorporation into erythrocytes 16 d after each 5 d NaPP: 57Fe feeding period. Data were analyzed using a linear regression model of log iron absorption on NaPP ratio, with body weight and baseline body iron stores as covariates and subject as a random intercept. RESULTS: Of the women included, 46% were anemic and 26% were iron deficient. Iron bioavailability was 10.8, 9.8, and 11.0% for the 0:1, 3:1, and 6:1 NaPP:57Fe treatments, respectively. There was no dose-response effect of an increasing NaPP:57Fe ratio (ß ± SE: 0.003 ± 0.028, P = 0.45). CONCLUSIONS: In this study, the addition of NaPP did not increase iron bioavailability from FePP-fortified bouillon cubes. However, iron bioavailability from the Nigerian meals prepared with FePP-fortified bouillon cubes was higher than expected. These results are encouraging for the potential of bouillon cubes as a fortification vehicle. Further studies are needed to assess the effect of FePP-fortified bouillon cubes on improving iron status in low-income populations. This trial was registered at clinicaltrials.gov as NCT02815449.
Assuntos
Anemia Ferropriva/prevenção & controle , Difosfatos/farmacologia , Difosfatos/farmacocinética , Alimentos Fortificados , Absorção Intestinal/efeitos dos fármacos , Ferro/farmacocinética , Refeições , Adulto , Anemia , Anemia Ferropriva/sangue , Disponibilidade Biológica , Estudos Cross-Over , Difosfatos/sangue , Difosfatos/uso terapêutico , Método Duplo-Cego , Eritrócitos/metabolismo , Feminino , Humanos , Ferro/sangue , Ferro/uso terapêutico , Isótopos de Ferro/sangue , Nigéria , Adulto JovemRESUMO
Ectopic mineralization is a global problem and leading cause of morbidity and mortality. The pathomechanisms of ectopic mineralization are poorly understood. Recent studies on heritable ectopic mineralization disorders with defined gene defects have been helpful in elucidation of the mechanisms of ectopic mineralization in general. The prototype of such disorders is pseudoxanthoma elasticum (PXE), a late-onset, slowly progressing disorder with multisystem clinical manifestations. Other conditions include generalized arterial calcification of infancy (GACI), characterized by severe, early-onset mineralization of the cardiovascular system, often with early postnatal demise. In addition, arterial calcification due to CD73 deficiency (ACDC) occurs late in life, mostly affecting arteries in the lower extremities in elderly individuals. These three conditions, PXE, GACI, and ACDC, caused by mutations in ABCC6, ENPP1, and NT5E, respectively, are characterized by reduced levels of inorganic pyrophosphate (PPi) in plasma. Because PPi is a powerful antimineralization factor, it has been postulated that reduced PPi is a major determinant for ectopic mineralization in these conditions. These and related observations on complementary mechanisms of ectopic mineralization have resulted in development of potential treatment modalities for PXE, including administration of bisphosphonates, stable PPi analogs with antimineralization activity. It is conceivable that efficient treatments may soon become available for heritable ectopic mineralization disorders with application to common calcification disorders.
Assuntos
5'-Nucleotidase/deficiência , Difosfonatos/uso terapêutico , Pseudoxantoma Elástico , Calcificação Vascular , Difosfatos/sangue , Proteínas Ligadas por GPI/deficiência , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo , Pseudoxantoma Elástico/sangue , Pseudoxantoma Elástico/tratamento farmacológico , Pseudoxantoma Elástico/genética , Pseudoxantoma Elástico/patologia , Pirofosfatases/genética , Pirofosfatases/metabolismo , Calcificação Vascular/sangue , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/genética , Calcificação Vascular/patologiaRESUMO
Pseudoxanthoma elasticum (PXE), a prototype of heritable ectopic mineralization disorders, is caused by mutations in the ABCC6 gene encoding a putative efflux transporter ABCC6. It was recently shown that the absence of ABCC6-mediated adenosine triphosphate release from the liver and, consequently, reduced inorganic pyrophosphate levels underlie the pathogenesis of PXE. Given that tissue-nonspecific alkaline phosphatase (TNAP), encoded by ALPL, is the enzyme responsible for degrading inorganic pyrophosphate, we hypothesized that reducing TNAP levels either by genetic or pharmacological means would lead to amelioration of the ectopic mineralization phenotype in the Abcc6-/- mouse model of PXE. Thus, we bred Abcc6-/- mice to heterozygous Alpl+/- mice that display approximately 50% plasma TNAP activity. The Abcc6-/-Alpl+/- double-mutant mice showed 52% reduction of mineralization in the muzzle skin compared with the Abcc6-/-Alpl+/+ mice. Subsequently, oral administration of SBI-425, a small molecule inhibitor of TNAP, resulted in 61% reduction of plasma TNAP activity and 58% reduction of mineralization in the muzzle skin of Abcc6-/- mice. By contrast, SBI-425 treatment of Enpp1 mutant mice, another model of ectopic mineralization associated with reduced inorganic pyrophosphate, failed to reduce muzzle skin mineralization. These results suggest that inhibition of TNAP might provide a promising treatment strategy for PXE, a currently intractable disease.
Assuntos
Niacinamida/análogos & derivados , Pseudoxantoma Elástico/tratamento farmacológico , Pirofosfatases/antagonistas & inibidores , Sulfonamidas/administração & dosagem , Trifosfato de Adenosina/metabolismo , Fosfatase Alcalina/genética , Fosfatase Alcalina/metabolismo , Animais , Difosfatos/sangue , Difosfatos/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Mutação , Niacinamida/administração & dosagem , Diester Fosfórico Hidrolases/genética , Diester Fosfórico Hidrolases/metabolismo , Pseudoxantoma Elástico/sangue , Pseudoxantoma Elástico/genética , Pirofosfatases/genética , Pirofosfatases/metabolismo , Pele/metabolismo , Pele/patologia , Calcificação Vascular/sangue , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/genéticaRESUMO
The lack of an effective drug therapy against ossification of spinal ligament (OSL) warrants investigation into the therapeutic target of this disease. An endogenous inhibitor of biomineralization, pyrophosphate (PPi) is a potential therapy for ectopic ossification; however, exogenous PPi is rapidly hydrolyzed by tissue non-specific alkaline phosphatase (TNAP) present in body fluids. In this study, we examined whether a drug therapy targeting PPi is efficacious for the treatment of OSL using the Enpp1ttw/ttw (twy) mouse model. Twenty male twy mice were randomized into four groups: (i) vehicle (Control); (ii) alkaline phosphatase inhibitor levamisole (5 mg/kg/day sc continuously); (iii) levamisole + exogenous PPi (160 µmol/kg/day sc continuously); and (iv) nuclear retinoic acid receptor-γ (RARγ) agonist (6 µg/kg sc daily). The RARγ agonist, which is a proven inhibitor of ectopic endochondral ossification, was used as a positive control. Treatments commenced when the mice were 5 weeks of age and continued for 4 weeks. Longitudinal micro-computed tomography and postmortem histological analysis were performed. Administration of levamisole alone and in combination with PPi increased serum PPi concentration by 17% and 52%, respectively, compared to that in vehicle-treated mice. The development of OSL in twy mice was suppressed by levamisole + PPi and RARγ agonist treatments, but not by levamisole alone. The levamisole + PPi therapy did not cause osteoporosis, whereas RARγ agonist-treated mice developed osteoporosis. Treatment of twy mice with levamisole in combination with exogenous PPi increased serum PPi level, which slowed the progression of OSL without producing adverse effect on bone. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1256-1261, 2018.
Assuntos
Antirreumáticos/uso terapêutico , Difosfatos/uso terapêutico , Levamisol/uso terapêutico , Ossificação do Ligamento Longitudinal Posterior/tratamento farmacológico , Animais , Antirreumáticos/farmacologia , Benzoatos , Remodelação Óssea/efeitos dos fármacos , Difosfatos/sangue , Difosfatos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Levamisol/farmacologia , Masculino , Camundongos , Terapia de Alvo Molecular , Naftóis , Distribuição AleatóriaRESUMO
Background: Ready-to-use-therapeutic foods (RUTFs) high in lipid, protein, and iron are used to treat malnutrition. Lipids increase gastric residence time, which could increase iron absorption, particularly from poorly soluble iron compounds and in combination with phytase.Objectives: The objectives were to 1) assess the effect on iron absorption of a lipid emulsion given 20 min before or together with an iron-fortified maize meal and 2) assess iron absorption from a micronutrient powder (MNP) given with a nutrient-dense RUTF and/or a microbial phytase.Design: A total of 41 women participated in 3 studies. They consumed a maize meal fortified with isotopically labeled ferrous sulfate (FeSO4; study 1) or ferric pyrophosphate (FePP; study 2). In studies 1 and 2, a lipid emulsion was given with or 20 min before the meal. In study 3, with the use of a 2 × 2 factorial design, subjects consumed a maize meal fortified with an MNP containing labeled FeSO4 (MNP) given with an RUTF (MNP+RUTF), with a phytase (MNP+phytase), or both (MNP+RUTF+phytase). Iron absorption was assessed by isotope incorporation in erythrocytes 14 d after the test meals.Results: The lipid emulsion given either before or with the meal significantly increased iron absorption from FePP by 2.55-fold (95% CI: 1.48-, 4.37-fold; P = 0.001) but not from FeSO4 There was a trend to increase iron absorption with the MNP+RUTF meal, which did not reach significance (1.21-fold; 95% CI: 0.92-, 1.61-fold; P = 0.060). The addition of phytase to MNP and MNP+RUTF significantly increased iron absorption by 1.85-fold (95% CI: 1.49-, 2.29-fold; P < 0.001), with no interaction between phytase and RUTF.Conclusions: In iron-fortified maize-based meals, the addition of lipids more than doubles iron absorption from FePP. Our results suggest the possibility of an enhancing effect on iron absorption of lipid-rich RUTFs, but more research is needed to determine this. This trial was registered at clinicaltrials.gov as NCT01991626.
Assuntos
6-Fitase/farmacologia , Alimentos Fortificados , Absorção Intestinal/efeitos dos fármacos , Ferro da Dieta/sangue , Ferro/sangue , Lipídeos/farmacologia , Micronutrientes/sangue , Adulto , Suplementos Nutricionais , Difosfatos/sangue , Eritrócitos/metabolismo , Feminino , Ferritinas/sangue , Humanos , Refeições , Pós , Adulto Jovem , Zea maysRESUMO
SUMMARY: Calcium supplements have been associated with increased cardiovascular risk, but the mechanism is unknown. We investigated the effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50). Changes in serum calcium were related to changes in T50. INTRODUCTION: Calcium supplements have been associated with increased cardiovascular risk; however, it is unknown whether this is related to an increase in vascular calcification. METHODS: We investigated the acute and 3-month effects of calcium supplements on the propensity of serum to calcify, based on the transition time of primary to secondary calciprotein particles (T50), and on three possible regulators of calcification: fetuin-A, pyrophosphate and fibroblast growth factor-23 (FGF23). We randomized 41 postmenopausal women to 1 g/day of calcium as carbonate, or to a placebo containing no calcium. Measurements were performed at baseline and then 4 and 8 h after their first dose, and after 3 months of supplementation. Fetuin-A, pyrophosphate and FGF23 were measured in the first 10 participants allocated to calcium carbonate and placebo who completed the study. RESULTS: T50 declined in both groups, the changes tending to be greater in the calcium group. Pyrophosphate declined from baseline in the placebo group at 4 h and was different from the calcium group at this time point (p = 0.04). There were no other significant between-groups differences. The changes in serum total calcium from baseline were significantly related to changes in T50 at 4 h (r = -0.32, p = 0.05) and 8 h (r = -0.39, p = 0.01), to fetuin-A at 3 months (r = 0.57, p = 0.01) and to pyrophosphate at 4 h (r = 0.61, p = 0.02). CONCLUSIONS: These correlative findings suggest that serum calcium concentrations modulate the propensity of serum to calcify (T50), and possibly produce counter-regulatory changes in pyrophosphate and fetuin-A. This provides a possible mechanism by which calcium supplements might influence vascular calcification.
Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Carbonato de Cálcio/efeitos adversos , Citrato de Cálcio/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Calcificação Vascular/induzido quimicamente , Idoso , Biomarcadores/sangue , Conservadores da Densidade Óssea/administração & dosagem , Cálcio/sangue , Carbonato de Cálcio/administração & dosagem , Citrato de Cálcio/administração & dosagem , Difosfatos/sangue , Esquema de Medicação , Feminino , Fator de Crescimento de Fibroblastos 23 , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Pessoa de Meia-Idade , Calcificação Vascular/sangue , alfa-2-Glicoproteína-HS/metabolismoRESUMO
OBJECTIVE: Mutations in ABCC6 underlie the ectopic mineralization disorder pseudoxanthoma elasticum (PXE) and some forms of generalized arterial calcification of infancy, both of which affect the cardiovascular system. Using cultured cells, we recently showed that ATP-binding cassette subfamily C member 6 (ABCC6) mediates the cellular release of ATP, which is extracellularly rapidly converted into AMP and the mineralization inhibitor inorganic pyrophosphate (PPi). The current study was performed to determine which tissues release ATP in an ABCC6-dependent manner in vivo, where released ATP is converted into AMP and PPi, and whether human PXE ptients have low plasma PPi concentrations. APPROACH AND RESULTS: Using cultured primary hepatocytes and in vivo liver perfusion experiments, we found that ABCC6 mediates the direct, sinusoidal, release of ATP from the liver. Outside hepatocytes, but still within the liver vasculature, released ATP is converted into AMP and PPi. The absence of functional ABCC6 in patients with PXE leads to strongly reduced plasma PPi concentrations. CONCLUSIONS: Hepatic ABCC6-mediated ATP release is the main source of circulating PPi, revealing an unanticipated role of the liver in systemic PPi homeostasis. Patients with PXE have a strongly reduced plasma PPi level, explaining their mineralization disorder. Our results indicate that systemic PPi is relatively stable and that PXE, generalized arterial calcification of infancy, and other ectopic mineralization disorders could be treated with PPi supplementation therapy.
Assuntos
Transportadores de Cassetes de Ligação de ATP/fisiologia , Trifosfato de Adenosina/metabolismo , Difosfatos/sangue , Fígado/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/fisiologia , Monofosfato de Adenosina/sangue , Idoso , Animais , Células Cultivadas , Meios de Cultivo Condicionados , Feminino , Células HEK293 , Células HeLa , Hepatócitos/metabolismo , Homeostase , Humanos , Fígado/irrigação sanguínea , Masculino , Camundongos , Pessoa de Meia-Idade , Pseudoxantoma Elástico/genética , Pseudoxantoma Elástico/metabolismo , RatosRESUMO
Pseudoxanthoma elasticum (PXE) is an autosomal recessive disease characterized by progressive ectopic mineralization of the skin, eyes, and arteries, for which no effective treatment exists. PXE is caused by inactivating mutations in the gene encoding ATP-binding cassette sub-family C member 6 (ABCC6), an ATP-dependent efflux transporter present mainly in the liver. Abcc6(-/-) mice have been instrumental in demonstrating that PXE is a metabolic disease caused by the absence of an unknown factor in the circulation, the presence of which depends on ABCC6 in the liver. Why absence of this factor results in PXE has remained a mystery. Here we report that medium from HEK293 cells overexpressing either human or rat ABCC6 potently inhibits mineralization in vitro, whereas medium from HEK293 control cells does not. Untargeted metabolomics revealed that cells expressing ABCC6 excrete large amounts of nucleoside triphosphates, even though ABCC6 itself does not transport nucleoside triphosphates. Extracellularly, ectonucleotidases hydrolyze the excreted nucleoside triphosphates to nucleoside monophosphates and inorganic pyrophosphate (PPi), a strong inhibitor of mineralization that plays a pivotal role in several mineralization disorders similar to PXE. The in vivo relevance of our data are demonstrated in Abcc6(-/-) mice, which had plasma PPi levels <40% of those found in WT mice. This study provides insight into how ABCC6 affects PXE. Our data indicate that the factor that normally prevents PXE is PPi, which is provided to the circulation in the form of nucleoside triphosphates via an as-yet unidentified but ABCC6-dependent mechanism.
Assuntos
Difosfatos/sangue , Doenças Metabólicas/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Pseudoxantoma Elástico/genética , Animais , Primers do DNA/genética , DNA Complementar/genética , Fosfatos de Dinucleosídeos/metabolismo , Células HEK293 , Humanos , Doenças Metabólicas/metabolismo , Doenças Metabólicas/patologia , Metabolômica , Camundongos , Camundongos Knockout , Mutagênese Sítio-Dirigida , Mutação/genética , Pseudoxantoma Elástico/metabolismo , Pseudoxantoma Elástico/patologia , RatosRESUMO
Generalized arterial calcification of infancy (GACI), an autosomal recessive disorder, is characterized by early mineralization of blood vessels, often diagnosed by prenatal ultrasound and usually resulting in demise during the first year of life. It is caused in most cases by mutations in the ENPP1 gene, encoding an enzyme that hydrolyzes ATP to AMP and inorganic pyrophosphate, the latter being a powerful anti-mineralization factor. Recently, a novel mouse phenotype was recognized as a result of ENU mutagenesis - those mice developed stiffening of the joints, hence the mutant mouse was named 'ages with stiffened joints' (asj). These mice harbor a missense mutation, p.V246D, in the Enpp1 gene. Here we demonstrate that the mutant ENPP1 protein is largely absent in the liver of asj mice, and the lack of enzymatic activity results in reduced inorganic pyrophosphate (PPi) levels in the plasma, accompanied by extensive mineralization of a number of tissues, including arterial blood vessels. The progress of mineralization is highly dependent on the mineral composition of the diet, with significant shortening of the lifespan on a diet enriched in phosphorus and low in magnesium. These results suggest that the asj mouse can serve as an animal model for GACI.
Assuntos
Diester Fosfórico Hidrolases/metabolismo , Pirofosfatases/metabolismo , Calcificação Vascular/enzimologia , Calcificação Vascular/patologia , Animais , Sequência de Bases , Calcificação Fisiológica , Cálcio/sangue , Cálcio/metabolismo , Análise Mutacional de DNA , Dieta , Difosfatos/sangue , Modelos Animais de Doenças , Técnicas de Genotipagem , Estimativa de Kaplan-Meier , Rim/metabolismo , Rim/patologia , Camundongos , Camundongos Mutantes , Dados de Sequência Molecular , Fenótipo , Diester Fosfórico Hidrolases/genética , Fósforo/sangue , Pirofosfatases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espectrometria por Raios X , Tomografia Computadorizada por Raios X , Calcificação Vascular/fisiopatologia , Vibrissas/diagnóstico por imagemRESUMO
Pyrophosphate (PPi) is a known inhibitor of hydroxyapatite formation and has been shown to inhibit medial vascular calcification in vitamin D-toxic rats. It was demonstrated recently that endogenous production of PPi prevents calcification of rat aorta that are cultured in high concentrations of calcium and phosphate. For determining whether PPi metabolism is altered in hemodialysis patients, plasma levels and dialytic clearance of PPi were measured in stable hemodialysis patients. Predialysis plasma [PPi] was 2.26 +/- 0.19 microM in 38 clinically stable hemodialysis patients compared with 3.26 +/- 0.17 in 36 normal subjects (P < 0.01). Approximately 30% of plasma PPi was protein bound, and this was not altered in dialysis patients. There was a weak inverse correlation with age in normal individuals but not in dialysis patients. Plasma [PPi] in dialysis patients was correlated with plasma [PO4(3-)] (r = 0.56) but not with [Ca2+], parathyroid hormone, or the dose of dialysis, and levels did not vary between interdialytic periods of 2 and 3 d. Plasma [PPi] decreased 32 +/- 5% after standard hemodialysis in 17 patients. In vitro clearance of PPi by a 2.1-m2 cellulose acetate dialyzer was 36%, and the mean PPi removal in five patients was 43 +/- 5 micromol, consistent with a similar in vivo clearance. Cleared PPi was greater than the plasma pool but less than the estimated extracellular fluid pool. Erythrocyte PPi content decreased 24 +/- 4%, indicating that intracellular PPi is removed as well. It is concluded that plasma [PPi] is reduced in hemodialysis patients and that PPi is cleared by dialysis. Plasma levels in some patients were below those that have previously been shown to prevent calcification of vessels in culture, suggesting that altered PPi metabolism could contribute to vascular calcification in hemodialysis patients.
Assuntos
Difosfatos/sangue , Diálise Renal/efeitos adversos , Adulto , Idoso , População Negra , Cálcio/metabolismo , Eritrócitos/metabolismo , Feminino , Humanos , Hidroxiapatitas/química , Falência Renal Crônica/terapia , Masculino , Pessoa de Meia-Idade , Fosfatos/metabolismo , Fósforo/sangue , Diálise Renal/métodos , Fatores de Tempo , Vitamina D/farmacologia , População BrancaRESUMO
31P-NMR spectra have been recorded on erythrocytes stored at 4 degrees C in various preservation media. Storage was always associated with an upfield shift of the inorganic phosphate (Pi) resonance and a pronounced upfield shift of the ATP beta resonance, indicating decreased intracellular pH (pHi) and decreased intracellular free magnesium ([Mg2+]i). The decreased [Mg2+]i occurred in preservation media not containing citrate and even in media supplemented with Mg2+. It could not be attributed to the changes in pHi, Na+, K+, lactate, Pi or 2,3-diphosphoglycerate, that occur with storage. The decrease in [Mg2+]i was largely reversed when stored cells were incubated for 1 h at 37 degrees C in fresh plasma. Stored cells were found to contain significant amounts of inorganic pyrophosphate, up to about 200 mumol per liter cell water. Being a tight binder of Mg2+, pyrophosphate could account for some of the observed decrease in [Mg2+]i. Additional mechanisms may involve precipitation of some other Mg2+ complex during cold storage or enhancement of Mg2+ binding to membrane components.
Assuntos
Preservação de Sangue/métodos , Eritrócitos/análise , Magnésio/sangue , Difosfatos/sangue , Humanos , Espectroscopia de Ressonância Magnética , Fatores de TempoRESUMO
1. Turkey poults were treated with graded doses (0-5% v/v) of ethanol for 6 weeks. Some birds were concomitantly injected intramuscularly with thiamin. 2. Erythrocyte transketolase (TK) activity was significantly decreased and the erythrocyte pyrophosphate (TPP) effect and blood concentrations of lactate and pyruvate were statistically greater in all ethanol-treated poults by 42 days. 3. Thiamin restored TK activity to normal levels and decreased the TPP effect and blood concentrations of lactate and pyruvate in ethanol poults. 4. Thiamin mitigated ethanol-induced cardiomyopathy in some 4-5% ethanol poults. 5. Thiamin had no significant effect on any of these parameters in control birds treated with thiamin.
Assuntos
Cardiomegalia/prevenção & controle , Etanol/antagonistas & inibidores , Tiamina/farmacologia , Animais , Cardiomegalia/induzido quimicamente , Difosfatos/sangue , Lactatos/sangue , Piruvatos/sangue , Transcetolase/sangue , PerusRESUMO
Soluble pyrophosphate was measured in the plasma and synovial fluid of various groups of patients and in the plasma of two control groups. The two control groups consisted of 13 healthy subjects and 19 patients suffering from benign lumbar back pain. The other group of patients had rheumatoid arthritis (RA) (14 plasma and 19 synovial fluid examinations), osteoarthrosis (OA) (19 plasma and 26 synovial fluids) and articular chondrocalcinosis (ACC) (27 plasma and 43 synovial fluids). The level of soluble pyrophosphate in the plasma was 3.5 mumol/l in healthy subjects, 4.0 mumol/l in patients with lumbar back pain, 4.1 mumol/l in individuals having OA and 3.5 mumol/l in the group suffering from RA as well as for those with ACC. The differences between these values are not significant statistically. In the synovial fluid the values were 4.6 mumol/l for the group with RA, 12.7 mumol/l for those with OA and 34.2 mumol/l in the group having ACC. If a normal distribution of these values is assumed and the average values and standard deviations recalculated for each group after elimination of cases more than 3 standard deviations above the mean, then we obtain 9.8 mumol/l for the group with OA and 23.8 mumol/l for those with ACC. The difference between the group with RA and that with OA is highly significant (p greater than 0.0001). Even more significant is the difference between the group with RA and ACC (p less than 0.0005). The difference between the OA and the ACC is also highly significant (p less than 0.001). On the basis of these observations various mechanisms leading to the pyrophosphage crystal deposition disease are discussed.