HSD3B1 (1245A>C) germline variant and clinical outcomes in metastatic castration-resistant prostate cancer patients treated with abiraterone and enzalutamide: results from two prospective studies.

BACKGROUND: A common polymorphism (1245A>C) in the HSD3B1 gene is associated with increased de novo synthesis of androgens and worse outcomes in men treated with androgen-deprivation therapy for metastatic castration-sensitive prostate cancer. The objective of the study was to determine whether this polymorphism is associated with outcomes for metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone or enzalutamide. PATIENTS AND METHODS: A total of 547 patients treated with abiraterone or enzalutamide from two prospective cohorts were evaluated. The HSD3B1 genotype was determined by targeted sequencing and/or TaqMan single-nucleotide polymorphism genotyping. In cohort 1, patients were randomized to receive abiraterone + prednisone or enzalutamide. In cohort 2, patients received either agent according to investigator's choice. Prostate-specific antigen (PSA) response rate, time to PSA progression (TTPP), time to progression (TTP) and overall survival were determined. Associations between HSD3B1 genotypes and outcomes were evaluated via univariate Cox regression. Multivariable Cox model was used to determine the independent association of each covariate. RESULTS: The HSD3B1 variant genotype (CC) was present in 15% of patients and was associated with worse TTP [hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.02-1.67, P = 0.032] and PSA response rates (48% for CC versus 62% and 65% for AA and AC, respectively [P = 0.019]), with no significant difference in TTPP (HR 1.28, 95% CI 0.99-1.66, P = 0.064). The effect of genotype was similar for treatment with abiraterone or enzalutamide with a negative test for interaction for TTPP (P = 0.997) and TTP (P = 0.749). Multivariable analysis did not show a significant association between genotype and TTP or TTPP. CONCLUSIONS: The HSD3B1 (CC) genotype was associated with shorter TTP and lower PSA response rate in patients with mCRPC treated with abiraterone or enzalutamide. However, the CC genotype did not provide prognostic information beyond that conferred by standard clinical variables, suggesting that it may not be a suitable stand-alone biomarker in mCRPC.

Ethical considerations in presymptomatic diagnosis of autosomal dominant spinocerebellar ataxias. / Consideraciones éticas en el diagnóstico presintomático de ataxias espinocerebelosas autosómico dominantes.

INTRODUCTION: Information on achieving presymptomatic diagnosis of spinocerebellar ataxia (SCA) is limited. The advent of molecular diagnosis makes it possible to identify the carriers of different diseases and has also introduced the prospect of detecting diseases even before their onset. This has drawn attention to the ethical implications that must be considered in these subjects with a view to preserving their physical and psychological well-being. DEVELOPMENT: SCA is composed of a group of neurodegenerative disorders with autosomal dominant inheritance. Only a few publications have described the genetic counselling processes and guidelines to be followed during the process of presymptomatic diagnosis (PSD). The size of the multidisciplinary teams, their areas of expertise, and the number of counselling sessions are different for each of the studies analysed here. However, the basis of presymptomatic diagnosis originates in common guidelines to which members of our team have contributed recently. CONCLUSION: Presymptomatic diagnosis should be performed according to guidelines that safeguard the subjects' welfare. The diagnostic process is only recommended for patients over 18 years old with symptoms suggesting SCA, and a minimum risk of 50%. Genetic counselling programmes must be available in all centres that offer presymptomatic diagnosis of SCA.

The health and technological implications of a better control of neoformed contaminants by the food industry.

The recent discovery of the presence of variable amounts of the carcinogenic compound acrylamide in a wide range of severely heat-treated food products, such as fried potatoes, biscuits, bread and coffee or malt, as a result of the heat process, has induced an important research in the area of the Maillard reaction in food. The interaction between a specific food composition and the heat process applied results in the development of complex oxidation and glycation reactions, which give rise to a mixture of flavoured compounds and possible neoformed contaminants (NFC). Recommendations by the European Commission aim at monitoring the content of major NFC, such as acrylamide and furan, in a list of food products commercialized in Europe. On the other hand, the Commission for European Normalization (CEN) has created recently a new workgroup (WG13) responsible for normalization of analytical method for NFC assessment. The European collective research ICARE was carried out to identify the possible health consequences of the ingestion of heat-treated products, characterize the reaction kinetics leading to NFC and evaluate some mitigation procedures proposed by the CIAA toolbox, and finally develop a simple, rapid and non destructive control method based on fluorescence acquisition on the crushed food products and chemometric analysis of the spectral information. This paper summarizes the objectives and essential results obtained in the scope of the project, highlighting the need for evaluating the distribution of NFC in food products commercialized in Europe, as well as the impact of the food formula/recipe and process on Maillard derived NFC food levels. The potential of the Fluoralys sensor regarding its ability to control food contamination with NFC is presented. A decrease in NFC concentration of heat processed food should allow significantly limiting the exposure of populations to NFC and consequently the potential related health risk.

Clinical Management of Cutaneous Adverse Events in Patients on Chemotherapy: A National Consensus Statement by the Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical Oncology. / Manejo clínico de los eventos adversos cutáneos en pacientes tratados con quimioterapia: consenso nacional de la Academia Española de Dermatología y Venereología y de la Sociedad Española de Oncología Médica.

Although the arrival of new chemotherapy drugs and combinations has brought progress in terms of cancer patient survival, they entail many adverse effects that can compromise treatment, and hence prognosis, of the disease. Cytostatic agents can cause dermatological toxicity, among other side effects. The most familiar adverse effect of chemotherapy is alopecia. Although not serious, this changes the outward appearance of cancer patients. Other adverse effects include hypersensitivity and photosensitivity reactions, hand-foot syndrome, epidermal necrolysis, recall reactions, scleroderma-like reactions, Raynaud's phenomenon, eccrine squamous syringometaplasia, neutrophilic eccrine hidradenitis, nail abnormalities, pigmentation changes and extravasation injuries. Onset of these adverse effects often causes dose reduction and/or delayed treatment, which can affect patient survival and quality of life. It is therefore important to prevent their occurrence and treat them promptly, which requires cooperation between medical oncologists and dermatologists. This article reviews chemotherapy-associated dermatological toxicity, along with its diagnosis and therapeutic management.

Clinical management of cutaneous adverse events in patients on targeted anticancer therapies and immunotherapies: a national consensus statement by the Spanish Academy of Dermatology and Venereology and the Spanish Society of Medical Oncology.

Progress in the understanding of many tumors has enabled the development of new therapies, such as those targeted at specific molecules involved in cell growth (targeted therapies) or intended to modulate the immune system (immunotherapy). However, along with the clinical benefit provided by these new treatments, new adverse effects have also appeared. Dermatological toxicities such as papulopustular eruptions, xerosis, and pruritus are common with EGFR inhibitors. Other adverse effects have also been described with PDGFR, BCR-ABL, and MAPK tyrosine kinase inhibitors, antiangiogenic drugs, and inhibitors at immune checkpoints such as CTLA-4 and PD-1/PD-L1. Onset of these adverse effects often causes dose reductions and/or delays in administering the prescribed therapy, which can affect patient survival and quality of life. It is, therefore, important to prevent the occurrence of these adverse effects, or to treat unavoidable ones as soon as possible. This requires cooperation between medical oncologists and dermatologists. This article reviews the various dermatological toxicities associated with targeted therapies and immunotherapies, along with their diagnosis and therapeutic management.

Strategy for the study of the health impact of dietary Maillard products in clinical studies: the example of the ICARE clinical study on healthy adults.

The study of the health impact of dietary Maillard products (MPs) in realistic clinical studies requires the design of nutritionally equivalent diets with high and low levels of MPs. This difficult challenge may be achieved by setting the high-MP diet at the regular daily level, where the common use of grilling, frying, and roasting processes allows significant amounts of carboxymethyllysine, hydroxymethylfurfural and acrylamide to be formed. In such conditions, we show that major lipid degradation does not occur, nor does degradation of vitamin E or thiamine. Based on this finding, the low-MP diet; must be constructed accordingly, by replacing all high-temperature techniques with steam cooking or the absence of cooking. The cooking fat must be replaced with similar raw fat as seasoning in the low-MP diet, the high caloric density resulting from water loss in the high-MP diet must be compensated by higher food quantities offered in the low-MP diet, and the vitamin loss in fruit and vegetables resulting from high temperatures in the high-MP diet can be circumvented by increasing the corresponding portion size. In the ICARE study, equilibrated diets were proposed, fulfilling all nutritional needs, but with a 3- to 45-fold difference in MP concentrations. Individual quantification of nutritional and MP intakes will ensure the nutritional equivalence of the two diets and allow for quantification of the specific impact of ingested MPs.

An immunohistochemical study of cytokeratins distribution of the human adult male and female urethra.

Surgical treatment of diseases affecting long urethral areas represents a challenge in urology. Recent developments of tissue-engineered urethral substitutes represent a hope for patients. However finding an ideal tissue source for urethral reconstruction first requires proper understanding of the native human urethra physiology and a deep knowledge of the histological and molecular features of the native human urethra. Here we present a comprehensive characterization of male and female urethra by histological, histochemical and immunohistochemical methods with a panel of 15 antibodies. The results demonstrated that the histology of the male and female urethra depend on the area where the sample is taken along its length. Proximal areas of male and female urethra have differential expression of the epithelial basal and suprabasal layer markers CK14 and CK10 which distinguished the prostatic/membranous and proximal female urethra from the bulbar/penile and distal female areas of the urethra. The distal male (penile) and female may be further divided by the distinct expression pattern of CK19. On the other hand, the expression of CK5/6 and CK19 also make a distinction of the proximal and distal female urethra. These results should facilitate a more informed selection of donor graft tissues for urethral replacement. Besides, novel bioengineered urethral tissue approaches should take into account the characterization of the different areas of the urethra presented in this work.

Performance of the clinical index of stable febrile neutropenia (CISNE) in different types of infections and tumors.

PURPOSE: The clinical index of stable febrile neutropenia (CISNE) can contribute to patient safety without increasing the complexity of decision-making. However, febrile neutropenia (FN) is a diverse syndrome. The aim of this analysis is to assess the performance of CISNE according to the type of tumor and infection and to characterize these patients. METHODS: We prospectively recruited 1383 FN episodes in situations of apparent clinical stability. Bonferroni-adjusted z tests of proportions were used to assess the association between the infections suspected at the time of onset and the type of tumor with the risk of serious complications and mortality. The performance of CISNE was appraised in each category using the Breslow-Day test for homogeneity of odds ratios and Forest Plots. RESULTS: 171 patients had a serious complication (12.3 %, 95 % confidence interval 10.7-14.2 %). The most common initial assumptive diagnoses were: fever without focus (34.5 %), upper respiratory infection (14.9 %), enteritis (12.7 %), stomatitis (11.8 %), and acute bronchitis (10.7 %). Lung and breast were the most common tumors, accounting for approximately 56 % of the series. The distribution of complications, mortality, and bacteremia varies for each of these categories. However, Breslow-Day tests indicate homogeneity of the odds ratio of the dichotomized CISNE score to predict complications in all infection and tumor subtypes. CONCLUSION: Despite FN's clinical and microbiological heterogeneity, the CISNE score was seen to be consistent and robust in spite of these variations. Hence, it appears to be a safe tool in seemingly stable FN.

Excitation energy transfer from tryptophan residues of peptides and intrinsic proteins to diphenylhexatriene in phospholipid vesicles and biological membranes.

An efficient excitation energy transfer from tryptophan residues of intrinsic membrane proteins to an extrinsic fluorescent probe (diphenylhexatriene) has been demonstrated in rat erythrocyte ghosts. To correlate this transfer with the localization of the probe, a model system has been investigated. It consists of peptides containing lysine and tryptophan residues bound to negatively charged phosphatidylserine vesicles. Absorption and fluorescence spectroscopies were used to follow peptide binding and diphenylhexatriene incorporation. Peptide binding is accompanied by a blue shift of the tryptophan fluorescence together with an increase of the quantum yield and of the fluorescence decay time. An experimental Föster critical distance value of 4.0 nm was found for energy transfer from tryptophan residues of peptides to diphenylhexatriene which approaches the range of calculated values (3.1-3.7 nm) using a two-dimensional model. These results demonstrate that efficient energy transfer can occur from tryptophan residues of intrinsic proteins to diphenylhexatriene without any interaction between diphenylhexatriene and proteins in biological membranes.

Monoclonal antibodies to human apolipoprotein A-I: characterization and application as structural probes for apolipoprotein A-I and high density lipoprotein.

Three mouse monoclonal antibodies (Mabs) to human apo A-I were produced using apolipoprotein A-I or HDL3 as immunogens. These monoclonal antibodies, 2G11, 4A12 and 4B11, were characterized for their reactivity with isolated apolipoprotein A-I and HDL in solution. The immunoblotting patterns of the HDL3 two-dimensional electrophoresis show that these three monoclonal antibodies reacted with all the polymorphic forms of apolipoprotein A-I. Cotitration experiments indicated that they correspond to three distinct epitopes. In order to locate these three antigenic determinants on the isolated apolipoprotein A-I, the reactivity of the three monoclonal antibodies has been studied on CNBr-cleaved apolipoprotein A-I. The monoclonal antibodies 2G11 and 4A12 addressed to the amino (CNBr 1) and carboxy (CNBr 4) terminal segments, respectively. In comparison with the monoclonal antibodies characterized by Weech et al. ((1985) Biochim. Biophys. Acta 835, 390-401), monoclonal antibody 4A12 is the only one described in the literature which is specific of the carboxy terminal segment of apolipoprotein A-I. Monoclonal antibody 4B11 does not react with any CNBr fragment, its binding is temperature dependent, it could be directed to a conformational epitope. Relative differences were demonstrated in the expression of the three epitopes in HDL subfractions isolated by density gradient ultracentrifugation. According to Curtiss and Edgington ((1985) J. Biol. Chem. 260, 2982-2993) our results indicate the existence of an immunochemical heterogeneity in the organization of apolipoprotein A-I at the surface of HDL particles as well as in the soluble form of apolipoprotein A-I.

Evaluation of the maillard reaction in infant formulas by means of front-face fluorescence.

Foods are complex mixtures of macro- and micronutrients, which interact, leading to oxidation, glycation, and hydrolysis upon heating (e.g., sterilization, cooking) and storage. Their nutritional quality and safety are consequently affected, justifying the need for accurate monitoring of the evolution of the food composition during processing and shelf life. Classical chromatographic analysis as well as newly proposed rapid methods based on fluorescence spectrometry analyses were applied on whey powder-based models and commercial samples (in powdered form and ultrahigh temperature [UHT] sterilized), some of which had been previously submitted to protein hydrolysis. These samples were incubated for 48 h at 60 degrees C to mimic accelerated storage. Fluorescence fingerprints addressing modifications in the product composition during processing were recorded and analyzed by chemometric methods. Carboxymethyllysine (Nepsilon-[carboxymethyl]lysine; CML) was measured using an ELISA method. Fluorescence, recorded in a front-face mode on intact samples, is very sensitive to pertinent physicochemical changes induced by heat treatment, formulation (the moisture level in powders, presence of vitamin C and iron), and storage. Similar trends were observed between powders' fluorescence and CML-for example, a strong effect of protein hydrolysis and increasing water content. Addition of vitamin C was associated with an antioxidant effect despite the presence of iron. Good calibration models were obtained for predicting CML from fluorescence spectra both in food models and in commercial samples, although more work is needed to obtain accurate and robust calibration models. Results show the potential of nondestructively applied fluorescence spectrometry for measuring CML in formulas, a rapid, simple, and cost-effective method to monitor formula quality.

Serine/threonine protein phosphatase 5 (PP5) participates in the regulation of glucocorticoid receptor nucleocytoplasmic shuttling.

BACKGROUND: In most cells glucocorticoid receptors (GR) reside predominantly in the cytoplasm. Upon hormone binding, the GR translocates into the nucleus, where the hormone-activated GR-complex regulates the transcription of GR-responsive genes. Serine/threonine protein phosphatase type 5 (PP5) associates with the GR-heat-shock protein-90 complex, and the suppression of PP5 expression with ISIS 15534 stimulates the activity of GR-responsive reporter plasmids, without affecting the binding of hormone to the GR. RESULTS: To further characterize the mechanism by which PP5 affects GR-induced gene expression, we employed immunofluorescence microscopy to track the movement of a GR-green fluorescent fusion protein (GR-GFP) that retained hormone binding, nuclear translocation activity and specific DNA binding activity, but is incapable of transactivation. In the absence of glucocorticoids, GR-GFP localized mainly in the cytoplasm. Treatment with dexamethasone results in the efficient translocation of GR-GFPs into the nucleus. The nuclear accumulation of GR-GFP, without the addition of glucocorticoids, was also observed when the expression of PP5 was suppressed by treatment with ISIS 15534. In contrast, ISIS 15534 treatment had no apparent effect on calcium induced nuclear translocation of NFAT-GFP. CONCLUSION: These studies suggest that PP5 participates in the regulation of glucocorticoid receptor nucleocytoplasmic shuttling, and that the GR-induced transcriptional activity observed when the expression of PP5 is suppressed by treatment with ISIS 15534 results from the nuclear accumulation of GR in a form that is capable of binding DNA yet still requires agonist to elicit maximal transcriptional activation.

The beta subunit of human rod photoreceptor cGMP-gated cation channel is generated from a complex transcription unit.

Human and bovine rod photoreceptor cGMP-gated cation channel consists of two subunits: alpha (63 kDa) and beta (240 kDa). The human beta subunit was shown to consist partly of sequence encoded by the cDNA clone hRCNC2b. Here we present the complete sequence of the human beta subunit and demonstrate that the previously reported human GAR1 gene encoding a glutamate-rich protein (hGARP) encodes its N-terminal portion. Using PCR, RNA blot and genomic DNA analysis, we provide evidence that the beta subunit is produced from a complex locus on chromosome 16 which is also capable of generating independent transcripts corresponding to GAR1 and the C-terminal two-thirds of the beta subunit. The results indicate that the beta subunit of the cGMP-gated cation channel is produced from an unusual locus consisting of more than one transcription unit.

Riboflavin photodegradation and photosensitizing effects are highly dependent on oxygen and ascorbate concentrations.

Riboflavin (RF) is a normal component of the eye lens which triggers a strong photosensitizing activity when exposed to light. Upon irradiation with short wavelength radiations below 400 nm, RF-photosensitized damage may occur. However, vitamin C is present at high concentrations in the normal lens and plays an important role in inhibiting these photosensitization processes. An in vitro simple model was used with the objective of understanding better the relationships between vitamin C and oxygen concentrations on the mechanisms of RF-mediated photodegradation of tryptophan (Trp), a target particularly sensitive to photo-oxidation. Under nitrogen, the RF decomposition reached its maximal value, and vitamin C and Trp photo-oxidation was negligible. When increasing oxygen pressure, RF photodegradation dropped and vitamin C photo-oxidation strongly increased and was maximal at 100% O2. RF-induced photodegradation of Trp first increased with oxygen concentration, up to 40 microM O2, and then decreased. RF and Trp degradation were significantly protected by vitamin C so that no more than 20% of the substrates concentration were oxidized in the presence of vitamin C higher than 0.8 mM. From our results we conclude that in the specific conditions of the normal lens, the high vitamin C concentration (2 mM) is compatible with the UVA radiation hazard, despite the presence of RF. However, if lenticular vitamin C decreases below 0.8 mM, photodegradation of RF may occur and Trp may therefore be photo-oxidized by a Type-I mechanism.

Copper chelation by tryptophan inhibits the copper-ascorbate oxidation of tryptophan.

The in vitro oxidation of tryptophan (Trp) by pro-oxidant systems such as iron-ascorbate indicates that Trp is a target for oxygen radicals in vivo. The Trp in albumin and lipoproteins has been reported to be actively oxidized by hydroxyl radical (HO(•)) generating systems such as copper-ascorbate or PUFA (polyunsaturated fatty acids) respectively. The super-physiological concentrations of the oxidants used in these studies prompted us to examine the effect of low copper and ascorbate concentrations on Trp oxidation. Trp (10-5000 µmol/L) was incubated with 1.5 µmol/L copper plus ascorbate (0.113 and 1.13 mmol/L) at 37°C and its oxidation followed by fluorescence and high-performance liquid chromatography. The percentage of Trp oxidized by the ascorbate-copper system was inversely related to its concentration and positively related to the ascorbate concentration. High concentrations of Trp (above 50 µmol/L for 0.113 mmol/L and 500 µmol/L for 1.13 mmol/L ascorbate) are not significantly oxidized in the presence of ascorbate. The large drop in the percentage Trp oxidation at higher concentrations may be due to the chelation of copper by Trp. High concentrations of Trp (over 50 µmol/L) strongly prevented ascorbate oxidation by copper, and therefore inhibited the production of HO(•) needed for Trp oxidation. Protein Trp is less readily oxidized by the ascorbate-copper system than free Trp. Proteins chelate copper much better than Trp, and so inhibit its oxidative activity, at least against ascorbic acid.

Lack of effect of copper on advanced Maillard reaction and glucose autoxidation at physiological concentrations of albumin.

This study examines the possible action of copper on advanced glycation. Copper has been shown to induce fluorescence due to advanced-glycated-end-products (AGEs) on albumin incubated with glucose, and this was interpreted as activation of the glucose or Amadori product (AP) autoxidation. We glycated albumin (60 g/L) to several levels with increasing concentrations of glucose. The dialysed glucose-free glycated albumin was then incubated with 1.5 µmol/L copper or 1 mmol/L diethylenetriaminepentaacetic acid (DTPA), plus or minus glucose. The production of AP, measured as furosine, was similar whether DTPA or copper was present in the incubation medium. It linearly increased as a function of time and glucose concentration in both cases up to a maximum (furosine around 20 mmol/g protein), indicating saturation of the free NH2 residues on the protein. The fluorescence due to AGEs increased linearly over time for glycated albumin incubated without glucose, and exponentially when glucose was added to the incubation medium. This fluorescence was also unaffected by DTPA or copper for a glucose concentration below 125 mmol/L and initial furosine below 10 mmol/g. However copper caused a slight activation in samples with very high glucose (1.25 mol/L) and furosine (30-40 mmol/g) concentrations. We therefore find no effect of copper in this experiment, because the copper concentration is lower and the albumin higher than that used in previous studies. In these conditions, albumin chelates copper and inhibits its oxidative activity. The protein concentrations used in most in vitro studies showing a copper effect were below 10 g/L with copper often above 10 µmol/L, so that copper may act oxidatively. As the lens and arterial wall have high protein concentrations, copper should have no action on protein glycation in vivo, unless altered protein structure impedes the inactivation of copper by chelation.

The fluorescence of advanced Maillard products is a good indicator of lysine damage during the Maillard reaction.

The objective of this study was to determine whether in heat-treated milk-resembling models or milk there is a lag phase, before lactulosyllysine (LL) is converted into advanced Maillard products (AMP), and if there is a step during the heat treatment where LL is actively degraded into AMP. For that purpose, a low temperature (60-85 degrees C) and a long heat treatment (15-90 h) were chosen. We observe that the heat treatment first induces a parallel increase in furosine and AMP fluorescence, confirming that AMP are produced very early during the heat treatment. At this step, both indicators are correlated with each other and precisely reflect the lysine damage. After a time, however, furosine reaches a steady-state concentration, whereas AMP fluorescence still increases, remaining correlated with the lysine blockage. Nevertheless, heat treatment applied to milk does not reach this step so that AMP fluorescence appears as a rapid alternative to furosine quantification.

The effects of 5% and 25% galactose diets on lens polyols, glutathione and protein glycation in male and female pigs.

The cataractogenic effect of a galactose diet was studied in male and female pigs in relation to the daily galactose intake. Two experiments were performed. In the first, 10 male and 10 female pigs were maintained on a 5% galactose diet for 30 days; galactose was given either as pure sugar or as hydrolyzed whey. In the second experiment, 18 castrated male and 21 female pigs were fed a 25% galactose diet for 49 days. Galactose was given as whey, hydrolyzed whey or as an alternating diet. Lenses were analyzed for sugar-alcohols, glutathione and protein glycation, and compared to lenses of pigs on a control standard diet. The 5% galactose diet induced large accumulation of dulcitol in the lens, which was similar whether galactose was ingested alone or as hydrolyzed whey. Glutathione and inositol contents were slightly below control values only in males on the galactose alone diet, perhaps indicating initiation of a cataractogenic process. No change was observed in females. The lenses of females on control diet were different from those of control males: having decreased glutathione, inositol and sorbitol contents and higher protein glycation. The 25% galactose diet resulted in an approximately 10 times higher lens dulcitol accumulation and advanced lens damage as measured by loss of inositol and increase in protein glycation. These changes were more severe in males than in females. The data indicate that there is a relationship between total galactose intake and dulcitol accumulation.

Antioxidant vitamins and degenerative pathologies. A review of vitamin C.

In this review we describe how tissues are protected against free radicals and we detail the mechanisms by which the insufficient reduction of ascorbate is involved in glycation and oxidation processes on proteins.