Mulberry Heart Disease and Hepatosis Dietetica in Farm Pigs (Sus scrofa domesticus) in a Research Setting.

Perioperative complications and deaths occurred while developing a novel surgical model of pediatric kyphosis in 10 to 12 kg male farm-raised Yorkshire piglets. All piglets appeared clinically normal preoperatively. Intraoperative complications included tachycardia, respiratory acidosis, and death. Postoperatively, clinical signs included posterior paresis, head pressing, prolonged anesthetic recovery, difficulty rising, and sudden death. Necropsies were performed on all piglets. Some morbidity and mortality were accurately attributed to the spinal surgery. However, the index piglet for this report died suddenly approximately 16 to 18 h after surgery. Necropsy of this animal revealed clear, serosanguineous pleural and pericardial effusions along with myocardial hemorrhage and hepatic lesions, consistent with mulberry heart disease and hepatosis dietetica, respectively. Serum vitamin E and selenium levels from this animal were below age-specific lab reference ranges. Clinical signs of vitamin E and selenium deficiency are most common in fast-growing weaner piglets. The added stress of major surgery may exacerbate the condition in young piglets. Resolution of morbidity and mortality in both juvenile and adult pigs occurred upon the use of an alternate vendor able to provide feed analyses meeting industry standards, although serum levels of vitamin E and selenium in similar ages and breed of swine were still occasionally slightly below reference ranges.

Fat soluble vitamins deficiency in pediatric chronic liver disease: The impact of liver transplantation.

BACKGROUND: Children affected with chronic liver disease are at risk for fat-soluble vitamins (FSV) deficiency, in this scenario the role of liver transplant has been only partially explored. AIMS: This study aimed to evaluate the prevalence of FSV deficiency in a cohort of paediatric patients awaiting liver transplant, analyze relationships between plasma vitamin concentrations and risk of acute rejections and liver fibrosis and assess the impact of the transplant on vitamin status. METHODS: 166 children candidates for liver transplant were retrospectively evaluated. Vitamin concentrations were measured before and 12 months after transplantation. RESULTS: Before transplant vitamin A, vitamin E and vitamin D deficiency was found in 66.6%, 40.6% and 36.3% of patients, respectively. 12 months after surgery, the prevalence of deficiency decreased to 29,5% and 2,6% for vitamin A and E while remained the same for vitamin D (36.3%). No association was found between vitamin status and the risk of acute rejections or the severity of liver fibrosis. CONCLUSION: Liver transplant was effective to improve vitamin A and E, but it did not affect vitamin D. A consensus is needed to define optimal nutritional management of these patients in order to prevent deficiencies.

Subacute combined degeneration associated with vitamin E deficiency due to small bowel obstruction: A case report.

RATIONALE: There have been a few reported cases of subacute combined degeneration (SCD) associated with vitamin E deficiency, but the period of intestinal malabsorption was more than several years. We present a rare case of acute onset SCD that occurred in a relatively short period of several weeks with vitamin E deficiency related to small bowel obstruction. PATIENT CONCERNS: A 50-year-old woman had abdominal pain. A small bowel obstruction was suspected and conservative treatment was performed. She underwent bowel surgery after 2 weeks without any improvement. Following the operation, she was in a state of reduced consciousness. She was treated in an intensive care unit. Her consciousness level gradually recovered to alert in a week, but other symptoms such as ataxia, weakness on limbs, severe dysarthria, and dysphagia occurred. Since then, she had spent nearly 6 weeks in a bed-ridden state without improving. DIAGNOSIS: SCD associated with vitamin E deficiency was confirmed by laboratory investigations, electrophysiologic test, and whole spine magnetic resonance imaging scans. INTERVENTIONS: For vitamin E supplementation, she was administered a dose of 1200 mg/d. Physical therapy was focused on strengthening exercise, balance, and walker gait training. Occupational therapy was focused on activities of daily living training and dysphagia rehabilitation. OUTCOMES: After 6 weeks, her muscle strengths and functional level were substantially improved. The vitamin E level was recovered to normal range. LESSONS: This case suggests that if neurological symptoms occur in patients with intestinal obstruction, clinicians need to consider a deficiency of micronutrients such as vitamin E and vitamin B12. Patients with short clinical courses suffer less neurological damage and achieve faster recovery.

Vitamin E status and its determinants in patients with cystic fibrosis.

PURPOSE: The risk of vitamin E deficiency is of primary concern in cystic fibrosis patients. However, early diagnosis and routine vitamin E supplementation can lead to its normal or even high levels. In the present study, we assessed vitamin E status in a large group of cystic fibrosis patients. Moreover, we also aimed to establish determinants of its body resources in cystic fibrosis patients. MATERIAL AND METHODS: The study group comprised 211 cystic fibrosis patients aged from 1 month to 48 years. In all of them serum α-tocopherol concentration was analyzed using high-performance liquid chromatography. RESULTS: Median vitamin E concentration was 9.9 µg/ml (1st-3rd quartile: 7.5-13.5). Vitamin E deficiency was found in 17 (8.0%) and high levels were documented in 24 (11.4%) participants. Patients with and without vitamin E deficiency did not differ significantly with respect to age, standardized body weight and height, FEV1, albumin concentration and vitamin E supplementation dose. However, vitamin E deficiency appeared more frequently in participants without vitamin E supplementation. Moreover, in multiple linear regression analysis pancreatic insufficiency, severe CFTR gene mutation and vitamin E dose, were potentially defined as determinants of vitamin E concentration. CONCLUSIONS: Vitamin E deficiency in cystic fibrosis patients is rather rare nowadays. Excessive vitamin E levels seem to be more frequent. Vitamin E status wasn't documented to be strictly related to clinical determinants. Beyond vitamin E supplementation, exocrine pancreatic function and CFTR gene mutations may have had an impact on the vitamin E body resources in cystic fibrosis patients.

Current and Promising Therapies in Autosomal Recessive Ataxias.

BACKGROUND & OBJECTIVE: Ataxia is clinically characterized by unsteady gait and imbalance. Cerebellar disorders may arise from many causes such as metabolic diseases, stroke or genetic mutations. The genetic causes are classified by mode of inheritance and include autosomal dominant, X-linked and autosomal recessive ataxias. Many years have passed since the description of the Friedreich's ataxia, the most common autosomal recessive ataxia, and mutations in many other genes have now been described. The genetic mutations mostly result in the accumulation of toxic metabolites which causes Purkinje neuron lost and eventual cerebellar dysfunction. Unfortunately, the recessive ataxias remain a poorly known group of diseases and most of them are yet untreatable. CONCLUSION: The aim of this review is to provide a comprehensive clinical profile and to review the currently available therapies. We overview the physiopathology, neurological features and diagnostic approach of the common recessive ataxias. The emphasis is also made on potential drugs currently or soon-to-be in clinical trials. For instance, promising gene therapies raise the possibility of treating differently Friedreich's ataxia, Ataxia-telangiectasia, Wilson's disease and Niemann-Pick disease in the next few years.

Vitamin E Deficiency and Oxidative Status are Associated with Prediabetes in Apparently Healthy Subjects.

BACKGROUND: Previous studies have indicated that vitamin E deficiency and oxidative stress affect the beta cell function. Hence, the aim of this study was to determine the association between vitamin E deficiency and oxidative status with prediabetes in apparently healthy subjects. METHODS: Apparently healthy men and women aged 18-65 years were enrolled in a case-control study. Individuals with new diagnosis of prediabetes were considered as cases and compared with a control group of individuals with normal glucose tolerance. Smoking, alcohol intake, pregnancy, diabetes, kidney disease, liver disease, cardiovascular disease, malignancy, glucocorticoid treatment and consumption of lipid-lowering drugs, antioxidants and vitamin supplements were exclusion criteria. Vitamin E deficiency was defined by serum levels of α-tocopherol <11.6 µmol/L, oxidative status was assessed by total antioxidant capacity and lipid peroxidation, and prediabetes was considered by the presence of impaired fasting glucose and/or impaired glucose tolerance. RESULTS: A total of 148 subjects were allocated into the case (n = 74) and control (n = 74) groups. The frequency of vitamin E deficiency was higher in the case group (41.8%) compared with the control group (35.1%), p = 0.03. The logistic regression analysis adjusted by age, waist circumference and body mass index, revealed a significant association between vitamin E deficiency (OR 3.23; 95% CI: 1.34-7.79, p = 0.009), lipoperoxidation (OR 2.82; CI 95%: 1.42-5.59, p = 0.003) and total antioxidant capacity (OR 0.93; CI 95%: 0.90-0.96, p <0.001) with prediabetes. CONCLUSIONS: Results of the present study suggest that both vitamin E deficiency and oxidative status are associated with prediabetes in apparently healthy subjects.

Lower Plasma Levels of Antioxidant Vitamins in Patients with Metabolic Syndrome: A Case Control Study.

BACKGROUND: Metabolic syndrome (MS) is a coexistence of metabolic risk factors affecting the development of cardiovascular diseases. Reactive oxygen species, which are excessively produced in MS, participate in its pathogenesis. Vitamins A, C and E are an important part of the non-enzymatic antioxidative barrier in humans. OBJECTIVES: The aim of the study was to estimate plasma vitamin A, C and E levels and the intake of these vitamins from the diet in patients with MS. MATERIAL AND METHODS: The study included 182 patients with MS, 94 men and 88 women, aged 30-65 years (mean 57.31 ± 8.28 years). The control group was comprised of 91 subjects, 56 men and 35 women, aged 41-65 years (mean 57.75 ± 5.84 years). The MS diagnosis was based on IDF criteria. The determination of the serum level of vitamin A, C and E was performed using the spectrophotometric method. The food intake was assessed by 24-h dietary recall. RESULTS: The mean plasma vitamin A, C and E levels were significantly lower in MS patients than in the controls (p = 0.05). No correlation was found between vitamin A, C and E intake from the diet and their plasma concentrations in MS patients. Plasma vitamin A, C and E deficiency was observed significantly more often in MS patients than in the control group (15.38% vs. 2.19%, 79.12% vs. 8.79% and 60.45% vs. 5.49%, p < 0.0001, respectively). BMI was the one factor significantly affecting the mean value of vitamin A, C and E levels in MS patients. CONCLUSIONS: MS patients demonstrated significantly lower plasma levels of vitamin A, C and E compared to the healthy subjects. Lower plasma levels of antioxidant vitamins with their high intake from the diet indicate antioxidant barrier impairment in MS patients.

Spontaneous decidualization in pseudopregnant rats with vitamin E deficiency.

Successful implantation of an embryo requires adequate depth of invasion in the endometrium, which depends upon decidualization. The aim of the present study was to elucidate why humans experience spontaneous decidualization and menstruation while most other mammals do not. We established a spontaneous decidualization model in pseudopregnant rats with vitamin E deficiency (VED) to investigate mechanisms associated with spontaneous decidualization. Vaginal smears were used to monitor bleeding while vitamin E levels were analyzed with a commercial vitamin E assay kit. Trypan blue staining was used to observe the implantation site at 5.5 days post-coitum (dpc). Uterine morphology, estradiol (E2) and progesterone levels, and the anti-oxidation system were evaluated at 5.5, 7.5, and 9.5 dpc. The proportion of rats in the VED group exhibiting endometrial bleeding gradually increased (5.9%, 32.3%, and 50%) over three consecutive cycles of pseudopregnancy. Vitamin E levels in the VED group were markedly lower compared to the control group in both the plasma and uterus, while the level of vitamin E in the liver did not differ between the control and VED groups. Spontaneous decidualization in the VED group was validated by histological examination and immunohistochemistry. At 5.5 dpc, the mean serum E2 level in the VED group was more than twice that of the control group. The mean total anti-oxidizing capability, catalase level, and glutathione peroxidase activity were significantly reduced in the decidualized portion of the VED group compared to controls, while the malondialdehyde level was also significantly higher in the decidualized portion of the VED group. We hypothesize that the E2 surge at 5.5 dpc and increasing levels of reactive oxygen species are responsible for spontaneous decidualization in VED rats.

A novel animal model of impaired glucose tolerance induced by the interaction of vitamin E deficiency and (60)Co radiation.

Impaired glucose tolerance (IGT), known as the prediabetes stage, is usually induced by habits of life or environmental factors. Established IGT animal models are mostly conducted with chemical compounds such as streptozocin or genetic modification. However, the occasion of exposure to these factors in daily life is seldom. The objective of this study was to establish a new animal model of IGT induced by VE deficiency in diet and exposure to radiation. SD rats were treated individually or in combination of these two factors. In the combination group, the calculated insulin sensitivity index decreased; then HOMA-ß value increased. Oxidative damage and IGT were observed. Insulin secretion level in perfusate from pancreas response to glucose was characterized by a rapid but reduced first phase and an obviously defective second phase upon pancreas perfusion. Histopathological images demonstrated the pathological changes. Western blotting analysis showed that the insulin signaling pathway was downregulated. The interaction of VE deficiency in diet and exposure to radiation could break the equilibrium of oxidation and antioxidation and result in IGT. More importantly, a new IGT model was successfully established which may be conducive to further research into development of drugs against human IGT.

Low serum concentrations of alpha-tocopherol are associated with increased risk of hip fracture. A NOREPOS study.

UNLABELLED: We investigated the risk of hip fracture according to circulating alpha-tocopherol, a plant-derived substance with antioxidant properties, in community-dwelling older Norwegians. We found a linear increasing risk of hip fracture with lower serum alpha-tocopherol concentrations, with a 51% higher risk in the lowest compared to the highest quartile. INTRODUCTION: Oxidative stress is a suggested contributing cause of osteoporosis and fractures. Vitamin E (α-tocopherol) has potent antioxidant properties in humans. The relationship between circulating α-tocopherol and fracture risk is not established. The aim of this study was to investigate the association between serum α-tocopherol concentrations and risk of hip fracture during up to 11 years of follow-up. METHODS: We performed a case-cohort analysis among 21,774 men and women aged 65-79 years who participated in four community-based health studies in Norway 1994-2001. Serum α-tocopherol concentrations at baseline were determined in 1,168 men and women who subsequently suffered hip fractures (median follow-up 8.2 years) and in a random sample (n = 1,434) from the same cohort. Cox proportional hazard regression adapted for gender-stratified case-cohort data was performed. RESULTS: Median (25, 75 percentile) serum α-tocopherol was 30.0 (22.6, 38.3) µmol/L, and it showed a linear inverse association with hip fracture: hazard ratio (HR) 1.11 (95% confidence interval (CI) 1.04-1.20) per 10-µmol/L decrease in serum α-tocopherol, adjusted for gender and study center. The lowest compared to the highest quartile conferred an HR of 1.51 (95% CI 1.17-1.95), adjusted for gender and study center. Adjustment for smoking, month of blood sample, BMI, education, physical inactivity, self-rated health, and serum 25-hydroxyvitamin D (25(OH)D) yielded similar results. Taking serum total cholesterol concentration into account attenuated the association somewhat: HR of hip fracture was 1.37 (95% CI 1.05-1.77) in first versus fourth quartile of serum α-tocopherol/total cholesterol ratio. CONCLUSIONS: Low serum concentrations of α-tocopherol were associated with increased risk of hip fracture in older Norwegians.

Intake and serum concentrations of α-tocopherol in relation to fractures in elderly women and men: 2 cohort studies.

BACKGROUND: A reduction in the formation of free radicals and oxidative stress might reduce the rate of bone loss and muscle wasting. OBJECTIVE: The objective was to determine whether α-tocopherol intake or serum concentrations are associated with fracture risk in older women and men. DESIGN: Two cohort studies, the Swedish Mammography Cohort (SMC; n = 61,433 women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n = 1138 men), were used. RESULTS: During 19 y of follow-up, 14,738 women in the SMC experienced a first fracture at any site (3871 hip fractures). A higher hip fracture rate was observed with lower intakes of α-tocopherol. Compared with the highest quintile of intake, the lowest quintile had a multivariable-adjusted HR of 1.86 (95% CI: 1.67, 2.06). The HR of any fracture was 1.20 (95% CI: 1.14, 1.28). α-Tocopherol-containing supplement use was associated with a reduced rate of hip fracture (HR: 0.78; 95% CI: 0.65, 0.93) and any fracture (HR: 0.86; 95% CI: 0.78, 0.94). Compared with the highest quintile of α-tocopherol intake in ULSAM (follow-up: 12 y), lower intakes (quintiles 1-4) were associated with a higher rate of hip fracture (HR: 3.33; 95% CI: 1.43, 7.76) and any fracture (HR: 1.84; 95% CI: 1.18, 2.88). The HR for hip fracture in men for each 1-SD decrease in serum α-tocopherol was 1.58 (95% CI: 1.13, 2.22) and for any fracture was 1.23 (95% CI: 1.02, 1.48). CONCLUSION: Low intakes and low serum concentrations of α-tocopherol are associated with an increased rate of fracture in elderly women and men.

[Therapeutic developments in chronic ataxias]. / Avances en el tratamiento de las ataxias crónicas.

Autosomal recessive cerebellar ataxias belong to a broader group of disorders known as inherited ataxias. In most cases onset occurs before the age of 20. These neurological disorders are characterized by degeneration or abnormal development of the cerebellum and spinal cord. Currently, specific treatment is only available for some of the chronic ataxias, more specifically those related to a known metabolic defect, such as abetalipoproteinemia, ataxia with vitamin E deficiency, and cerebrotendinous xanthomatosis. Treatment based on a diet with reduced intake of fat, supplementation of oral vitamins E and A, and the administration of chenodeoxycholic acid could modify the course of the disease. Although for most of autosomal recessive ataxias there is no definitive treatment, iron chelators and antioxidants have been proposed to reduce the mitochondrial iron overload in Friederich's ataxia patients. Corticosteroids have been used to reduce ataxia symptoms in ataxia telangiectasia. Coenzyme Q10 deficiency associated with ataxia may be responsive to Co Q10 or ubidecarenone supplementations. Early treatment of these disorders may be associated with a better drug response.

Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice.

RATIONALE: Growing evidence indicates that oxidative stress contributes markedly to endothelial dysfunction. The selenoenzyme glutathione peroxidase 4 (Gpx4) is an intracellular antioxidant enzyme important for the protection of membranes by its unique activity to reduce complex hydroperoxides in membrane bilayers and lipoprotein particles. Yet a role of Gpx4 in endothelial cell function has remained enigmatic. OBJECTIVE: To investigate the role of Gpx4 ablation and subsequent lipid peroxidation in the vascular compartment in vivo. METHODS AND RESULTS: Endothelium-specific deletion of Gpx4 had no obvious impact on normal vascular homeostasis, nor did it impair tumor-derived angiogenesis in mice maintained on a normal diet. In stark contrast, aortic explants from endothelium-specific Gpx4 knockout mice showed a markedly reduced number of endothelial branches in sprouting assays. To shed light onto this apparent discrepancy between the in vivo and ex vivo results, we depleted mice of a second antioxidant, vitamin E, which is normally absent under ex vivo conditions. Therefore, mice were fed a vitamin E-depleted diet for 6 weeks before endothelial deletion of Gpx4 was induced by 4-hydroxytamoxifen. Surprisingly, ≈80% of the knockout mice died. Histopathological analysis revealed detachment of endothelial cells from the basement membrane and endothelial cell death in multiple organs, which triggered thrombus formation. Thromboembolic events were the likely cause of various clinical pathologies, including heart failure, renal and splenic microinfarctions, and paraplegia. CONCLUSIONS: Here, we show for the first time that in the absence of Gpx4, sufficient vitamin E supplementation is crucial for endothelial viability.

Low vitamin and carotenoid levels are related to cerebral white matter lesions.

PURPOSE: To determine the effects of vitamins and carotenoids on brain white matter lesions (WMLs), we examined the associations between WMLs with vitamin and carotenoid levels in Japanese middle-aged and elderly subjects. SUBJECTS AND METHODS: Four-hundred and sixty-nine healthy participants (male = 317; female = 152) that underwent medical examinations were examined. Deep white matter lesions (DWLs) were detected via magnetic resonance imaging (MRI) in 39 subjects. We evaluated the effects of vitamin and carotenoid levels on DWLs via logistic regression analysis. RESULTS: Lower gamma-tocopherol levels were significantly associated with DWLs in all subjects. While lower gamma-tocopherol and vitamin C levels were significantly associated with DWLs in males, lower delta-tocopherol levels were associated with DWLs in females. The associations between DWLs and lower gamma- and delta-tocopherol and vitamin C levels were independent of age, hypertension, or smoking. However, the associations between DWLs and lower alfa-tocopherol were not significant following adjustments for smoking. CONCLUSION: Lower carotenoid and vitamin levels were independently associated with cerebral DWLs in Japanese subjects.

Chronic vitamin E deficiency promotes vitamin C deficiency in zebrafish leading to degenerative myopathy and impaired swimming behavior.

We hypothesized that zebrafish (Danio rerio) undergoing long-term vitamin E deficiency with marginal vitamin C status would develop myopathy resulting in impaired swimming. Zebrafish were fed for 1 y a defined diet without (E-) and with (E+) vitamin E (500 mg α-tocopherol/kg diet). For the last 150 days, dietary ascorbic acid concentrations were decreased from 3500 to 50 mg/kg diet and the fish sampled periodically to assess ascorbic acid concentrations. The ascorbic acid depletion curves were faster in the E- compared with E+ fish (P < 0.0001); the estimated half-life of depletion in the E- fish was 34 days, while in it was 55 days in the E+ fish. To assess swimming behavior, zebrafish were monitored individually following a "startle-response" stimulus, using computer and video technology. Muscle histopathology was assessed using hematoxylin and eosin staining on paramedian sections of fixed zebrafish. At study end, E- fish contained 300-fold less α-tocopherol (p < 0.0001), half the ascorbic acid (p = 0.0001) and 3-fold more malondialdehyde (p = 0.0005) than did E+ fish. During the first minute following a tap stimulus (p < 0.05), E+ fish swam twice as far as did E- fish. In the E- fish, the sluggish behavior was associated with a multifocal, polyphasic, degenerative myopathy of the skeletal muscle. The myopathy severity ranged from scattered acute necrosis to widespread fibrosis and was accompanied by increased anti-hydroxynonenal staining. Thus, vitamin E deficiency in zebrafish causes increased oxidative stress and a secondary depletion of ascorbic acid, resulting in severe damage to muscle tissue and impaired muscle function.

Avances en el tratamiento de las ataxias crónicas / [Therapeutic developments in chronic ataxias].

Autosomal recessive cerebellar ataxias belong to a broader group of disorders known as inherited ataxias. In most cases onset occurs before the age of 20. These neurological disorders are characterized by degeneration or abnormal development of the cerebellum and spinal cord. Currently, specific treatment is only available for some of the chronic ataxias, more specifically those related to a known metabolic defect, such as abetalipoproteinemia, ataxia with vitamin E deficiency, and cerebrotendinous xanthomatosis. Treatment based on a diet with reduced intake of fat, supplementation of oral vitamins E and A, and the administration of chenodeoxycholic acid could modify the course of the disease. Although for most of autosomal recessive ataxias there is no definitive treatment, iron chelators and antioxidants have been proposed to reduce the mitochondrial iron overload in Friederich’s ataxia patients. Corticosteroids have been used to reduce ataxia symptoms in ataxia telangiectasia. Coenzyme Q10 deficiency associated with ataxia may be responsive to Co Q10 or ubidecarenone supplementations. Early treatment of these disorders may be associated with a better drug response.

Vitamin E decreases bone mass by stimulating osteoclast fusion.

Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. Osteoclasts are multinucleated cells that are formed by mononuclear preosteoclast fusion. Fat-soluble vitamins such as vitamin D are pivotal in maintaining skeletal integrity. However, the role of vitamin E in bone remodeling is unknown. Here, we show that mice deficient in α-tocopherol transfer protein (Ttpa(-/-) mice), a mouse model of genetic vitamin E deficiency, have high bone mass as a result of a decrease in bone resorption. Cell-based assays indicated that α-tocopherol stimulated osteoclast fusion, independent of its antioxidant capacity, by inducing the expression of dendritic-cell-specific transmembrane protein, an essential molecule for osteoclast fusion, through activation of mitogen-activated protein kinase 14 (p38) and microphthalmia-associated transcription factor, as well as its direct recruitment to the Tm7sf4 (a gene encoding DC-STAMP) promoter. Indeed, the bone abnormality seen in Ttpa(-/-) mice was rescued by a Tm7sf4 transgene. Moreover, wild-type mice or rats fed an α-tocopherol-supplemented diet, which contains a comparable amount of α-tocopherol to supplements consumed by many people, lost bone mass. These results show that serum vitamin E is a determinant of bone mass through its regulation of osteoclast fusion.