Cuidado con la biotina: un problema creciente en la práctica clínica / Awareness of biotin: A growing problem in clinical practice

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Higher fish consumption and lower risk of central nervous system demyelination.

BACKGROUND/OBJECTIVES: The evidence for diet as a risk factor for multiple sclerosis (MS) is inconclusive. We examined the associations between fish consumption and risk of a first clinical diagnosis of central nervous system demyelination (FCD), a common precursor to MS. METHODS: The 2003-2006 Ausimmune Study was a case-control study examining environmental risk factors for FCD, with participants recruited from four regions of Australia and matched on age, sex, and study region. Dietary intake data were collected using a food frequency questionnaire. We used conditional logistic regression models to test associations between fish consumption (total, tinned, grilled, and fried) and risk of FCD (249 cases and 438 controls), adjusting for history of infectious mononucleosis, smoking, serum 25-hydroxyvitamin D concentrations, socio-economic status, omega-3 supplement use, dietary under-reporting, and total energy intake. RESULTS: Higher total fish consumption (per 30 g/day, equivalent to two serves/week) was associated with an 18% reduced risk of FCD (AOR 0.82; 95% CI 0.70, 0.97). While we found no statistically significant associations between grilled and fried fish consumption and risk of FCD, higher tinned fish consumption (per 30 g/day) was associated with a 41% reduced risk of FCD (AOR 0.59; 95% CI 0.39, 0.89). CONCLUSIONS: Tinned fish is predominantly oily, whereas grilled and fried fish are likely to be a combination of oily and white types. Oily fish is high in vitamin D and very long chain polyunsaturated omega-3 fatty acids, both of which may be beneficial in relation to MS.

Control of seizures by ketogenic diet-induced modulation of metabolic pathways.

Epilepsy is too complex to be considered as a disease; it is more of a syndrome, characterized by seizures, which can be caused by a diverse array of afflictions. As such, drug interventions that target a single biological pathway will only help the specific individuals where that drug's mechanism of action is relevant to their disorder. Most likely, this will not alleviate all forms of epilepsy nor the potential biological pathways causing the seizures, such as glucose/amino acid transport, mitochondrial dysfunction, or neuronal myelination. Considering our current inability to test every individual effectively for the true causes of their epilepsy and the alarming number of misdiagnoses observed, we propose the use of the ketogenic diet (KD) as an effective and efficient preliminary/long-term treatment. The KD mimics fasting by altering substrate metabolism from carbohydrates to fatty acids and ketone bodies (KBs). Here, we underscore the need to understand the underlying cellular mechanisms governing the KD's modulation of various forms of epilepsy and how a diverse array of metabolites including soluble fibers, specific fatty acids, and functional amino acids (e.g., leucine, D-serine, glycine, arginine metabolites, and N-acetyl-cysteine) may potentially enhance the KD's ability to treat and reverse, not mask, these neurological disorders that lead to epilepsy.

Chondroitin sulfate proteoglycans in demyelinated lesions impair remyelination.

OBJECTIVE: Failure of remyelination is a critical impediment to recovery in multiple sclerosis (MS). Chondroitin sulfate proteoglycans (CSPGs) have been reported to accumulate in MS lesions, and we thus examined the functional roles of CSPGs on oligodendrocyte precursor cells (OPCs), oligodendrocytes, and remyelination. METHODS: We evaluated the expression of CSPGs in lysolecithin-injected mouse spinal cord, an animal model of demyelination and spontaneous remyelination. The functional impact of CSPGs on OPCs and remyelination was investigated using cultured adult murine and human OPCs and by treating demyelinated mice with xyloside to reduce the CSPG deposition that occurred following injury. RESULTS: Early and robust upregulation of CSPGs following lysolecithin-induced demyelination was cleared during remyelination. In culture, CSPGs anchored onto the substratum reduced the adhesion of mouse and human OPCs and their subsequent morphological differentiation into process-bearing oligodendrocytes. Soluble CSPGs added to already adherent OPCs reduced the development of processes, whereas the acquisition of mature myelin proteins was unimpeded. Stripe assays of alternating CSPG and control substrata confirmed the nonpermissive nature of CSPGs for OPC adhesion and morphological differentiation. Enzymatic degradation of CSPGs with chondroitinase ABC was sufficient to overcome CSPG-dependent inhibition of human oligodendrocytes. Finally, in vivo xyloside treatment to reduce CSPG synthesis in lysolecithin-demyelinated mice increased numbers of OPCs and oligodendrocytes in lesions, and culminated in improved remyelination. INTERPRETATION: These results identify CSPGs as a nonpermissive substrate for OPCs and oligodendrocytes, and as a prominent impediment to remyelination. The data suggest the requirement for the neutralization of CSPGs for repair after demyelination.

Methionine adenosyltransferase I/III deficiency: neurological manifestations and relevance of S-adenosylmethionine.

Methionine adenosyltransferase I/III (MAT I/III) deficiency, caused by mutations in the MAT1A gene, is an inherited metabolic disorder characterized by persistent hypermethioninemia, usually detected by newborn mass screening. There is a wide range of clinical manifestations, from completely asymptomatic to neurological problems associated with brain demyelination. Physiological role of S-adenosylmethionine (SAM), the metabolic product of methionine catalyzed by MAT, in the central nervous system has been investigated in vivo and in vitro, and case reports demonstrated an effectiveness of supplementary treatment of SAM in the improvement of neurological development and myelination. Methionine restriction can be an additional therapeutic strategy because hypermethioninemia alone may be neurotoxic; however, lowering methionine carries a risk to decrease the synthesis of SAM.

Effects of dietary intervention on MRI activity, de- and remyelination in the cuprizone model for demyelination.

Whether differences in diet composition may influence demyelinating diseases remains controversial. The aim of this study was to analyse if diets with a different composition of polyunsaturated fatty acids (PUFAs) could influence demyelination and remyelination in cuprizone fed mice, a widely used animal model for de- and remyelination. C57Bl/6 mice were fed with 0.2% cuprizone on three different diets. The diets consisted of the same ingredients, except the lipid source, which came from 1) salmon fillets rich in marine n-3 polyunsaturated fatty acids (PUFAs), 2) cod liver oil rich in marine n-3 PUFAs, or 3) a control diet containing soybean oil rich in n-6 PUFAs. After 5 weeks of cuprizone treatment, the mice given salmon-cuprizone had significantly less hyperintense lesion volume on brain magnetic resonance imaging (MRI) than the two other groups (P<0.0005). After 6 weeks of cuprizone treatment, the salmon-cuprizone group had less demyelination in the corpus callosum, as measured with luxol fast blue (LFB) (P<0.0005) and anti-proteolipid protein (PLP) (P=0.014). The salmon-cuprizone group also had enhanced remyelination compared to the cod liver oil-cuprizone group (LFB; P=0.003, PLP; P=0.018). This study indicates that a fish rich diet may offer a protective role in demyelination. The source of N-3 PUFAs, or other components in the fish, may be important, as no effect of a cod liver oil based diet was observed. This may be of importance related to the discrepant results in dietary intervention studies for demyelinating diseases.

RSH/SLO (Smith-Lemli-Opitz) syndrome: designing a high cholesterol diet for the SLO syndrome.

A high cholesterol diet has been suggested to help prevent the poor reproductive outcomes found in heterozygote carriers of fetuses affected with the Smith-Lemli-Opitz (SLO) syndrome. The theory has also been presented that a high cholesterol medical food may enhance myelination of the central nervous system of the infant and prevent demyelination in the child and adult with SLO. Clinical studies are required to test this hypothesis and to determine the optimal composition of such medical foods. FDA requires proof of efficacy and controls nutrient composition, ingredients, and label claims of medical foods.