Comparative proteomics illustrates the complexity of Fe, Mn and Zn deficiency-responsive mechanisms of potato (Solanum tuberosum L.) plants in vitro.

MAIN CONCLUSION: The present study is the first to integrate physiological and proteomic data providing information on Fe, Mn and Zn deficiency-responsive mechanisms of potato plants in vitro. Micronutrient deficiency is an important limiting factor for potato production that causes substantial tuber yield and quality losses. To under the underlying molecular mechanisms of potato in response to Fe, Mn and Zn deficiency, a comparative proteomic approach was applied. Leaf proteome change of in vitro-propagated potato plantlets subjected to a range of Fe-deficiency treatments (20, 10 and 0 µM Na-Fe-EDTA), Mn-deficiency treatments (1 and 0 µM MnCl2·4H2O) and Zn-deficiency treatment (0 µM ZnCl2) using two-dimensional gel electrophoresis was analyzed. Quantitative image analysis showed a total of 146, 55 and 42 protein spots under Fe, Mn and Zn deficiency with their abundance significantly altered (P < 0.05) more than twofold, respectively. By MALDI-TOF/TOF MS analyses, the differentially abundant proteins were found mainly involved in bioenergy and metabolism, photosynthesis, defence, redox homeostasis and protein biosynthesis/degradation under the metal deficiencies. Signaling, transport, cellular structure and transcription-related proteins were also identified. The hierarchical clustering results revealed that these proteins were involved in a dynamic network in response to Fe, Mn and Zn deficiency. All these metal deficiencies caused cellular metabolic remodeling to improve metal acquisition and distribution in potato plants. The reduced photosynthetic efficiency occurred under each metal deficiency, yet Fe-deficient plants showed a more severe damage of photosynthesis. More defence mechanisms were induced by Fe deficiency than Mn and Zn deficiency, and the antioxidant systems showed different responses to each metal deficiency. Reprogramming of protein biosynthesis/degradation and assembly was more strongly required for acclimation to Fe deficiency. The signaling cascades involving auxin and NDPKs might also play roles in micronutrient stress signaling and pinpoint interesting candidates for future studies. Our results first provide an insight into the complex functional and regulatory networks in potato plants under Fe, Mn and Zn deficiency.

The mechanism of iron-compensation for manganese deficiency of Streptococcus pneumoniae.

Given their involvement in catalysis, infection, and biofilm formation, Fe and Mn are essential for bacterial survival and virulence. In this study, we found that Streptococcus pneumoniae (S. pneumoniae) could grow in the Mn-deficient medium (MDCM). Furthermore, findings showed that the Fe concentration in the bacterium increased when the Mn concentration decreased. In addition, it was noted that supplementing MDCM with Fe resulted in the recovery of bacterial growth. Quantitative proteomics using stable-isotope dimethyl labeling was performed to investigate the adaptive growth mechanism of S. pneumoniae under Mn-deficient conditions. It was found that the expression levels of 25 proteins were downregulated, whereas those of 54 proteins were upregulated in S. pneumoniae grown in MDCM. It was also noted that several of the downregulated proteins were involved in cell energy metabolism, amino acid synthesis, and reduction of oxidation products. More importantly, several ATP-binding cassette transporters related to Fe uptake, such as PiuA, PiaA, PitA, and SPD_1609, were overexpressed for increased Fe uptake from the MDCM. The results suggest that Mn deficiency disturbs multiple metabolic processes in S. pneumoniae. Furthermore, it causes a compensatory effect of Fe for Mn, which is beneficial for the survival of the bacterium in extreme environments. SIGNIFICANCE: The relationship between manganese and iron metabolism in S. pneumoniae has not been clearly revealed. In this paper, we suggest that Mn limitation disturbs multiple metabolic processes and evidently decreases the ATP level in the bacterium. In order to survive in this extreme environment, bacteria upregulated three type of Fe ion transporters PiuABC (heme), PiaABC (ferrichrome) and PitABC (Fe3+) to uptake enough Fe ions to response to Mn deficiency. Therefore, this study reveals a bacterial mechanism of Fe compensation for Mn, and provides new insight for investigating the relativeness of Fe and Mn metabolism of bacteria.

Trace elements in the liver of captive and free-ranging European bison (Bison bonasus L.).

European bison is classified as a vulnerable species because of many threats. We analyzed the content of toxic and essential elements (Ag, Al, As, Ba, Be, Cd, Co, Cr, Cu, Hg, Mg, Mn, Na, Ni, Pb, Se, Th, Tl, U, V, and Zn) in the livers of 30 captive and free-ranging European bison from the Bison Breeding Center in Smardzewice and from Bialowieza Primeval Forest in Poland. The contents of toxic elements were lower than reported previously in European Bison and were similar to those of wild ungulates from non-polluted areas. Accumulation of Cd and Cr was related to the age of animals. We compared the mineral status between captive and free-ranging European bison to verify whether the maintenance type could affect concentrations of trace elements in the liver. The concentration of Mn and Zn differed between captive and free-ranging group. Our results were compared to the reference values of essential elements for cattle. All animals from this study were Se-deficient and more than 80% of them have Cu deficiency. Deficiency of Mn was present in 20% of captive and 37% of free-ranging animals whereas Zn in 37% and 3% respectively. Statistical analysis confirmed that Mn and Zn deficiencies were related o the maintenance of animals (p<0.05). We revealed that mineral deficiencies could be an additional threat to the Polish population of European bison. Thus, the monitoring of essential minerals is necessary and future work is required to optimize the supplementation and foddering for preventing the occurrence of mineral deficiencies.

Manganese Provision in Parenteral Nutrition: An Update.

Manganese (Mn) is an essential micronutrient required for the activity of metalloenzymes. It is an essential component of parenteral nutrition (PN), but requirements are low. Mn status is difficult to assess, with the commonest method being measurement of its concentration in whole blood. This method has limitations, including artifactually high concentrations resulting from contamination of specimen tubes. Mn toxicity is a well-recognized complication of PN, the risk of which increases if there is cholestasis or if the patient has received high doses. It usually presents with parkinsonian-like symptoms but may be detected presymptomatically as hypermanganesemia or as increased signal intensity of the basal ganglia upon T1-weighted magnetic resonance imaging. Caution is necessary when providing Mn for patients on long-term PN (>1 month). It is advisable to withhold supplementation if hypermanganesemia or cholestasis develops. Deficiency of Mn is rare in patients treated with PN. PN regimens are contaminated with Mn in amounts likely to meet requirements. Consequently, it is debated whether PN should be routinely supplemented with Mn. The currently recommended dose of Mn in adults treated with PN is 55 µg/d, but the doses provided by most currently available multi-trace element products exceed this. In response to calls for new products to be developed, 2 new multi-trace element products are currently available in Europe that provide Mn doses of 55 µg/d. Once these products are in general use, it is likely that the incidence of Mn toxicity will decrease.

Assessing Selenium, Manganese, and Iodine Status in Pediatric Patients Receiving Parenteral Nutrition.

BACKGROUND: Pediatric patients who are receiving parenteral nutrition (PN) unsupplemented with trace minerals can become deficient. Due to shortages in trace mineral products and the 2004 American Society for Parenteral and Enteral Nutrition report stating that individualized trace element supplementation may be warranted, a review was conducted concerning the trace minerals selenium (Se), manganese (Mn), and iodine (I). METHOD: A retrospective review of pediatric patients receiving PN that contained Se and Mn was conducted to determine if a difference existed between them and patients receiving PN without Se and Mn. Statistical analysis was done to assess a difference between trace mineral levels and the time to deficiency between supplemented and unsupplemented patients. Unsupplemented I patients had urine I levels assessed to determine deficiencies in patients receiving PN. RESULTS: Plasma Se levels were measured at a mean of 20 days for supplemented patients (n = 131) and 19 days for nonsupplemented patients (n = 57) with no difference between groups ( P = .2973). Plasma Mn levels were measured at a mean of 28 days, showing no statistical difference ( P = .721). Of the 177 nonsupplemented I patients, 74% demonstrated I deficiencies without supplementation. CONCLUSIONS: Time to the development of a Se, Mn, or I deficiency is important to guide supplementation of exclusive PN in children when trace mineral products are short in supply. Our retrospective experience supports assessment of the trace minerals Se at 21 days and Mn at 30 days. It also suggests that some pediatric patients receiving PN are deficient in I.

A SLC39A8 variant causes manganese deficiency, and glycosylation and mitochondrial disorders.

SLC39A8 variants have recently been reported to cause a type II congenital disorder of glycosylation (CDG) in patients with intellectual disability and cerebellar atrophy. Here we report a novel SLC39A8 variant in siblings with features of Leigh-like mitochondrial disease. Two sisters born to consanguineous Lebanese parents had profound developmental delay, dystonia, seizures and failure to thrive. Brain MRI of both siblings identified bilateral basal ganglia hyperintensities on T2-weighted imaging and cerebral atrophy. CSF lactate was elevated in patient 1 and normal in patient 2. Respiratory chain enzymology was only performed on patient 1 and revealed complex IV and II + III activity was low in liver, with elevated complex I activity. Complex IV activity was borderline low in patient 1 muscle and pyruvate dehydrogenase activity was reduced. Whole genome sequencing identified a homozygous Chr4(GRCh37):g.103236869C>G; c.338G>C; p.(Cys113Ser) variant in SLC39A8, located in one of eight regions identified by homozygosity mapping. SLC39A8 encodes a manganese and zinc transporter which localises to the cell and mitochondrial membranes. Patient 2 blood and urine manganese levels were undetectably low. Transferrin electrophoresis of patient 2 serum revealed a type II CDG defect. Oral supplementation with galactose and uridine led to improvement of the transferrin isoform pattern within 14 days of treatment initiation. Oral manganese has only recently been added to the treatment. These results suggest SLC39A8 deficiency can cause both a type II CDG and Leigh-like syndrome, possibly via reduced activity of the manganese-dependent enzymes ß-galactosyltransferase and mitochondrial manganese superoxide dismutase.

Trace Element Status (Zinc, Copper, Selenium, Iron, Manganese) in Patients with Long-Term Home Parenteral Nutrition.

BACKGROUND: The objective of the present study was to determine concentrations of zinc (Zn), copper (Cu), iron (Fe), selenium (Se) in blood plasma and manganese (Mn) in the whole blood in patients with long-term home parenteral nutrition (HPN) in comparison to the control group. PATIENTS AND METHODS: We examined 68 patients (16 men and 52 women) aged from 28 to 68 years on a long-term HPN lasting from 4 to 96 months. The short bowel syndrome was an indication for HPN. The daily doses of Zn, Cu, Fe, Se and Mn in the last 3 months were determined. RESULTS: No significant differences in blood plasma were found for Zn, Cu and Fe in patients with HPN and in the control group (p > 0.05). The concentration of Mn in whole blood was significantly increased in HPN patients (p < 0.0001), while Se concentration in these patients was significantly decreased (p < 0.005). The concentration of Mn in the whole blood of 16 patients with cholestasis was significantly increased compared to the patients without cholestasis (p < 0.001). The Cu concentration was increased with no statistical significance. CONCLUSION: In long-term HPN, the status of trace elements in the patients has to be continually monitored and the daily substitution doses of these elements have to be flexibly adjusted. Dosing schedule needs to be adjusted especially in cases of cholestatic hepatopathy. A discussion about the optimal daily dose of Mn in patients on HPN is appropriate. For clinical practice, the availability of a substitution mixture of trace elements lacking Mn would be advantageous.

SLC39A8 Deficiency: A Disorder of Manganese Transport and Glycosylation.

SLC39A8 is a membrane transporter responsible for manganese uptake into the cell. Via whole-exome sequencing, we studied a child that presented with cranial asymmetry, severe infantile spasms with hypsarrhythmia, and dysproportionate dwarfism. Analysis of transferrin glycosylation revealed severe dysglycosylation corresponding to a type II congenital disorder of glycosylation (CDG) and the blood manganese levels were below the detection limit. The variants c.112G>C (p.Gly38Arg) and c.1019T>A (p.Ile340Asn) were identified in SLC39A8. A second individual with the variants c.97G>A (p.Val33Met) and c.1004G>C (p.Ser335Thr) on the paternal allele and c.610G>T (p.Gly204Cys) on the maternal allele was identified among a group of unresolved case subjects with CDG. These data demonstrate that variants in SLC39A8 impair the function of manganese-dependent enzymes, most notably ß-1,4-galactosyltransferase, a Golgi enzyme essential for biosynthesis of the carbohydrate part of glycoproteins. Impaired galactosylation leads to a severe disorder with deformed skull, severe seizures, short limbs, profound psychomotor retardation, and hearing loss. Oral galactose supplementation is a treatment option and results in complete normalization of glycosylation. SLC39A8 deficiency links a trace element deficiency with inherited glycosylation disorders.

HAIR HEAVY METAL AND ESSENTIAL TRACE ELEMENT CONCENTRATION IN CHILDREN WITH AUTISM SPECTRUM DISORDER.

Our study aims evaluation of level of essential trace elements and heavy metals in the hair samples of children with autistic spectrum disorder (ASD) and identification of changes that are associated with autistic spectrum disorders. Case-control study was conducted at Child Development Center of Iashvili Children's Central Hospital (LD).We studied 60 children aged from 4 to 5 years old. The concentrations of 28 elements among (Ca,Zn, K, Fe, Cu, Se, Mn, Cr, S, Br, Cl, Co, Ag, V, Ni, Rb, Mo, Sr, Ti, Ba, Pb, As, Hg, Cd, Sb, Zr, Sn, Bi) them trace elements and toxic metals) were determined in scalp hair samples of children (n=30) with autistic spectrum disorder (ASD) and from control group of healthy children (n=30) with matched sex and age. Micro-elemental status was detected in the hair, with roentgen-fluorescence spectrometer method (Method MBИ 081/12-4502-000, Apparatus ALVAX- CIP, USA - UKRAIN) .To achieve the similarity of study and control groups, pre and postnatal as well as family and social history were assessed and similar groups were selected. Children with genetic problems, malnourished children, children from families with social problems were excluded from the study. The diagnosis of ASD were performed by pediatrician and psychologist (using M-CHAT and ADOS) according to DSM IV (Diagnostic and Statistical Manual of Mental Disorders from the American Psychiatric association) criteria. The study was statistically analyzed using computer program SPSS 19. Deficiencies of essential trace microelements revealed in both group, but there was significant difference between control and studied groups. The most deficient element was zinc (92% in target and 20% in control), then - manganese (55% and 8%) and selenium (38% and 4%). In case of cooper study revealed excess concentration of this element only in target group in 50% of cases. The contaminations to heavy metals were detected in case of lead (78% and 16), mercury (43% and 10%) and cadmium (38% and 8%). The study statistical results indicated, that deficient concentrations of trace elements such as zinc, manganese, molybdenum and selenium in hair significantly linked with ASD (Kramer's V was 0,740; 0,537; 0,333; 0,417 accordingly). In case of cooper we got excess levels of this element and this data was highly linked with autism spectrum disorder. We got high associations and significant values between of lead, mercury and cadmium concentrations and ASD. Study results indicate that there are significant differences of hair essential trace elements concentrations in children with autism spectrum disorder comparing with healthy children group. The result obtained also showed high contamination to heavy metals such as lead, mercury and cadmium in ASD children compared to healthy ones. So, our study demonstrated alteration in levels of toxic heavy metals and essential trace elements in children with autistic spectrum disorders as compared to healthy children. This suggests a possible pathophysiological role of heavy metals and trace elements in the genesis of symptoms of autism spectrum disorders.

A pilot duplicate diet study on manganese, selenium and chromium intakes in institutionalised children and adolescents from Guatemala.

Hidden hunger occurs in the presence of an otherwise nutritionally or energetically appropriate diet that is deficient in essential vitamins and minerals. Guatemala has the highest rate of child malnutrition in Latin America and the prevalence of hidden hunger is high. The aim of this study was to determine the Mn, Se and Cr dietary intakes in Guatemalan institutionalised children (4-14 years), a population group at high risk of mineral deficiency. For this purpose, the contents of Mn, Se and Cr were analysed in a duplicate diet (for 7 consecutive days) by electrothermal atomisation-atomic absorption spectrophotometry following acid digestion. Mn, Se and Cr intakes from the duplicate diets were in the range of 1·3-2·31 mg/d, 58·7-69·6 µg/d and 6·32-27·57 µg/d, respectively. Mn and Cr values were below current recommended daily intakes. A cereal- and legumes-based diet is habitually consumed by this population. Local vegetables, fruits and nutritional supplements are included daily, but the consumption of fish, meat, eggs and dairy products is very infrequent or negligible. Mean daily energy intake from the 7-d diet was 8418·2 kJ (2012 kcal), with a macronutrient energy distribution of carbohydrates 69·4 %, proteins 12·3 % and fats 18·3 %. Correlations between Mn, Se and Cr intakes and energy and other nutrient intakes were also evaluated. The present findings will help establish new nutritional strategies for this and similar population groups.

Are additional trace elements necessary in total parenteral nutrition for patients with esophageal cancer receiving cisplatin-based chemotherapy?

It is known that cisplatin induces the excretion of zinc from the urine and thereby reduces its serum concentration. However, the fluctuation of these trace elements during or after cisplatin-based chemotherapy has not been evaluated. To answer this question, we performed a clinical study in esophageal cancer patients undergoing cisplatin-based chemotherapy. Eighteen patients with esophageal cancer who were not able to swallow food or water orally due to complete stenosis of the esophagus were evaluated. The patients were divided into a control group [total parenteral nutrition (TPN) alone for 28 days, ten cases] and an intervention group (TPN with additional trace elements for 28 days, eight cases). The serum concentrations of zinc, iron, copper, manganese, triiodothyronin (T3), and thyroxin (T4), as alternative indicators of iodine, were measured on days 0, 14, and 28 of treatment, and statistically analyzed on day 28. In the control group, the serum concentration of copper was significantly decreased from 135.4 (day 0) to 122.1 µg/ml (day 14), and finally to 110.6 µg/ml (day 28, p = 0.015). The concentration of manganese was also significantly decreased from 1.34 (day 0) to 1.17 µg/ml (day 14) and finally to 1.20 (day 28, p = 0.049). The levels of zinc, iron, T3, and T4 were not significantly changed. In the intervention group, the supplementation with trace elements successfully prevented these decreases in their concentrations. TPN with supplementary trace elements is preferable and recommended for patients who are undergoing chemotherapy in order to maintain the patients' nutrient homeostasis.

Role of trace elements in parenteral nutrition support of the surgical neonate.

BACKGROUND: Parenteral nutrition (PN) has transformed the outcome for neonates with surgical problems in the intensive care unit. Trace element supplementation in PN is a standard practice in many neonatal intensive care units. However, many of these elements are contaminants in PN solutions, and contamination levels may, in themselves, be sufficient for normal metabolic needs. Additional supplementation may actually lead to toxicity in neonates whose requirements are small. METHODS: An electronic search of the MEDLINE, Cochrane Collaboration, and SCOPUS English language medical databases was performed for the key words "trace elements," "micro-nutrients," and "parenteral nutrition additives." Studies were categorized based on levels of evidence offered, with randomized controlled trials and meta-analyses accorded the greatest importance at the apex of the data pool and case reports and animal experiments the least importance. Articles were reviewed with the primary goal of developing uniform recommendations for trace element supplementation in the surgical neonate. The secondary goals were to review the physiologic role, metabolic demands, requirements, losses, deficiency syndromes, and toxicity symptoms associated with zinc, copper, chromium, selenium, manganese, and molybdenum supplementation in PN. RESULTS: Zinc supplementation must begin at initiation of PN. All other trace elements can be added to PN 2 to 4 weeks after initiation. Copper and manganese need to be withheld if the neonate develops PN-associated liver disease. The status of chromium supplementation is currently being actively debated, with contaminant levels in PN being sufficient in most cases to meet neonatal requirements. Selenium is an important component of antioxidant enzymes with a role in the pathogenesis of neonatal surgical conditions such as necrotizing enterocolitis and bronchopulmonary dysplasia. Premature infants are often selenium deficient, and early supplementation has shown a reduction in sepsis events in this age group. CONCLUSION: Appropriate supplementation of trace elements in surgical infants is important, and levels should be monitored. In certain settings, it may be more appropriate to individualize trace element supplementation based on the predetermined physiologic need rather than using bundled packages of trace elements as is the current norm. Balance studies of trace element requirements should be performed to better establish clinical recommendations for optimal trace element dosing in the neonatal surgical population.

Manganese source affects manganese transport and gene expression of divalent metal transporter 1 in the small intestine of broilers.

In the present study, two experiments were conducted to investigate the effect of Mn source on Mn transport and the expression of a Mn transporter, divalent metal transporter 1 (DMT1), in the small intestine of broilers. In Expt 1, in situ ligated duodenal loops from Mn-deficient chicks (29-d-old) were perfused with solutions containing 0-8.74 mmol Mn/l from either MnSO4, or one of two organic chelates of Mn and amino acids with moderate (OM) or strong (OS) chelation strength (Q(f)) up to 30 min. In Expt 2, Mn-deficient intact broilers (14-d-old) were fed a control diet (12.45 mg Mn/kg) or the control diet supplemented with 100 mg Mn/kg as one of all Mn sources for 14 d. The uptake kinetics of Mn from different Mn sources in the ligated duodenal loops followed a saturable process as determined by regression analysis of concentration-dependent uptake rates. The maximum transport rate (Jmax) and K(m) values, and DMT1 mRNA levels in the ligated duodenal loops were higher (P < 0.01) for OM and OS than for MnSO4. DMT1 mRNA levels were much higher (P < 0.01) in the duodenum than in the jejunum and ileum. Both DMT1 mRNA levels in the duodenum and plasma Mn contents from the hepatic portal vein of intact chicks on day 14 post-feeding increased (P < 0.05) in the following order: control < MnSO4 < OM < OS. These results indicated that organic Mn sources with stronger Q(f) showed higher Mn transport and absorption, and DMT1 might be involved in the regulation of organic Mn transport in the proximal small intestine of broilers.

Novel high-throughput assay to assess cellular manganese levels in a striatal cell line model of Huntington's disease confirms a deficit in manganese accumulation.

In spite of the essentiality of manganese (Mn) as a trace element necessary for a variety of physiological processes, Mn in excess accumulates in the brain and has been associated with dysfunction and degeneration of the basal ganglia. Despite the high sensitivity, limited chemical interference, and multi-elemental advantages of traditional methods for measuring Mn levels, they lack the feasibility to assess Mn transport dynamics in a high-throughput manner. Our lab has previously reported decreased net Mn accumulation in a mutant striatal cell line model of Huntington's disease (STHdh(Q111/Q111)) relative to wild-type following Mn exposure. To evaluate Mn transport dynamics in these striatal cell lines, we have developed a high-throughput fluorescence-quenching extraction assay (Cellular Fura-2 Manganese Extraction Assay - CFMEA). CFMEA utilizes changes in fura-2 fluorescence upon excitation at 360 nm (Ca(2+) isosbestic point) and emission at 535 nm, as an indirect measurement of total cellular Mn content. Here, we report the establishment, development, and application of CFMEA. Specifically, we evaluate critical extraction and assay conditions (e.g. extraction buffer, temperature, and fura-2 concentration) required for efficient extraction and quantitative detection of cellular Mn from cultured cells. Mn concentrations can be derived from quenching of fura-2 fluorescence with standard curves based on saturation one-site specific binding kinetics. Importantly, we show that extracted calcium and magnesium concentrations below 10 µM have negligible influence on measurements of Mn by fura-2. CFMEA is able to accurately measure extracted Mn levels from cultured striatal cells over a range of at least 0.1-10 µM. We have used two independent Mn supplementation approaches to validate the quantitative accuracy of CFMEA over a 0-200 µM cellular Mn-exposure range. Finally, we have utilized CFMEA to experimentally confirm a deficit in net Mn accumulation in the mutant HD striatal cell line versus wild-type cells. To conclude, we have developed and applied a novel assay to assess Mn transport dynamics in cultured striatal cell lines. CFMEA provides a rapid means of evaluating Mn transport kinetics in cellular toxicity and disease models.

[The relationship of clinical and morphological characteristics of chronic gastritis with microelements deficiency].

We aimed to analyze the interconnection of chronic gastritis clinicopathologic characteristics with the content of selenium, zinc and manganese in blood serum. It is stated that the concentration of the microelements being studied (mostly selenium) is the prognostic indication of prescription of inflammatory process in the mucous coat of stomach and its clinical activity (pain and dyspeptic syndrome intensity), and the degree of microelements deficiency increases proportionally with intensity augmentation of atrophic processes in stomach.

Consequences of dietary manganese and copper imbalance on neuronal apoptosis in a murine model of scrapie.

AIMS: Copper and manganese levels are altered in mice both lacking PrPc and prion-infected brains. The aim of this study was to analyse the effects of manganese and copper imbalance on neuronal apoptosis in a scrapie-infected Tga20 mouse model. METHODS: Immunoreactivities for the apoptotic proteins Bax and active caspase-3 were evaluated in nine regions of the brain of scrapie-infected and control Tga20 mice treated with one of several diets: depleted cooper (-Cu), loaded manganese (+Mn), depleted copper/loaded manganese (-Cu+Mn) and regular diet. Immunohistochemical determination of NeuN was used to detect possible neuronal loss. RESULTS: Intracellular Bax detection was significantly decreased in animals fed with modified diets, particularly in those treated with copper-depleted diets. A decrease in active caspase-3 was primarily observed in animals fed with enhanced manganese diets. Our results show that the -Cu, -Cu+Mn and +Mn diets protected against apoptosis in scrapie-infected mice. However, NeuN immunolabelling quantification revealed that no diet was sufficient to arrest neuronal death. CONCLUSIONS: With regard to apoptosis induction, the response of Tga20 mice to prion infection was similar to that reported for other mice models. Our results demonstrate the neuroprotective effects of -Cu, -Cu+Mn and +Mn diets in a murine model of scrapie. However, neuronal death induced by infection with prions seems to be independent of apoptosis marker signalling. Moreover, copper-modified diets were neuroprotective against the possible toxicity of the prion transgene in Tga20 control and infected mice even though manganese supplementation could not counteract this toxicity.

Manganese in parenteral nutrition: who, when, and why should we supplement?

Micronutrient requirements are not fully understood. Parenteral nutrition (PN) usually contains the trace element (TE) manganese (Mn) from fixed-concentration TE supplements. Multiple TE formulations may not be optimal in pediatric and home PN. Moreover, most PN products contain Mn as a ubiquitous contaminant. Excessive Mn can lead to Parkinson-like symptoms resulting from hypermanganesemia. A survey of 40 Australasian hospitals that contributed data on 108 patients to the annual home PN register and a systematic review of the literature were conducted to establish the scope of the potential problem of Mn toxicity in PN patients. Exposure to Mn doses 5-6 times current daily requirements, together with the TE contamination that is reported in PN products, can lead to neurotoxicity. Whole-blood levels are more accurate for monitoring and correlate well with signal intensity of magnetic resonance imaging. Current TE formulations restrict prescribing options. The regulatory mechanisms of Mn homeostasis are bypassed via the parenteral route so elimination via the hepatobiliary system is impaired, resulting in tissue or brain accumulation. Published dosage recommendations may be excessive and official guidelines require revision. Variability in clinical practices necessitates that individual TE additives are more widely available and multiple TE products reformulated. More frequent monitoring for any brain accumulation is recommended. The scarcity of PN-associated Mn deficiency, plus the growing evidence for Mn toxicity, leads to the conclusion that it is unnecessary for Mn to be prescribed routinely for pediatric or long-term PN patients.

Feeding a low manganese diet to heifers during gestation impairs fetal growth and development.

A study was conducted to examine the effects of low dietary Mn on growth performance of pregnant heifers and fetal development of their offspring. Twenty pregnant Angus (n = 9) and Simmental (n = 11) heifers averaging 17 mo of age and 447.6 kg of initial body weight were used in the 267-d study. Heifers were selected from a previous study examining the effects of supplemental Mn on growth and reproductive performance of heifers. Ten pregnant heifers per treatment from the control (analyzed at 15.8 mg of Mn/kg of DM) and supplemental Mn (50 mg/kg of DM) treatments were randomly selected at the conclusion of the previous study to continue on their respective dietary treatments through gestation and early lactation. Serum cholesterol for the 267-d period was not affected by treatment. Whole-blood Mn concentration of heifers on d 267 was not affected by treatment. Whole-blood Mn concentration at birth was lower in calves born to control heifers than in those born to supplemented heifers. Calves born to control heifers weighed less at birth than those born to heifers receiving supplemental Mn. Calves born to control heifers suffered from varying signs of Mn deficiency, including superior brachygnathism, unsteadiness, disproportionate dwarfism, and swollen joints. Results suggest that feeding gestating heifers a diet containing 16.6 mg of Mn/kg of DM is not adequate for proper fetal development. Supplementation of 50 mg of Mn/kg of DM to the control diet was sufficient to overcome any signs of Mn deficiency in calves.

Dietary manganese suppresses alpha1 adrenergic receptor-mediated vascular contraction.

We examined the effect of dietary manganese (Mn) on the vascular contractile machinery in rat thoracic aortas. Weanling male Sprague-Dawley rats were fed either an Mn-deficient (MnD), Mn-adequate (MnA) or Mn-supplemented (MnS) diet (<1, 10-15 and 45-50 ppm Mn, respectively). After 15 weeks on the diets the rats were sacrificed and 3-mm aortic rings were contracted in six cumulative doses of the alpha(1) adrenergic receptor agonist L-phenylephrine (l-Phe, 10(-8) to 3 x 10(-6) M) under 1.5-g preload and relaxed with one dose of acetylcholine (3 x 10(-6) M) to assess intact endothelium. The maximal force (F(max)) of contraction and relaxation, as well as the vessel sensitivity (pD(2)) were determined. Manganese deficiency, assessed by hepatic Mn content, significantly lowered the rate of animal growth. A two-way analysis of variance revealed that MnS animals developed lower F(max) when contracted with L-Phe compared with the MnD and MnA animals (P

O uso das panelas de ferro como suprimento das necessidades de ferro: [revisão] / Role of iron cookware in supplying the daily iron requirement: [review]

A anemia ferro piva é considerada o principal problema nutricional a ser vencido na atualidade. Segundo dados publicados pela Organização Mundial da Saúde, há cerca de dois bilhões de pessoas portadoras dessa anemia. A fortificação de alimentos industrializados e o tratamento médico com sulfato ferro são as formas mais usadas no combate à doença, ambos com sucesso parcial. Entretanto, o uso de utensílios culinários de ferro no preparo das refeições também tem sido apontado, por alguns pesquisadores, como solução alternativa no tratamento e prevenção desta anemia. É essa solução alternativa que o presente artigo visa discutir, bem como os cuidados necessários e a indicação e contra-indicação da utilização destes utensílios, fazendo uma ampla revisão da literatura científica com objetivo de fornecer subsídio técnico científico aos profissionais que atuam na área da saúde pública, abordando a forma como os mesmos podem auxiliar na prevenção e combate da anemia ferropriva com eficiência.

Data published by the World Health Organization show that there are aroundtwo billion people in the world with iron deficiency anemia. Iron deficiency anemia is currently considered the number one public nutrition problem to be solved. Enrichment of processed foods and medical treatment with iron supplementation were the usual forms to fight the disease, both with limited success. The use of iron pans in food preparation has been pointed by some researchers as an alternative solution to treat and prevent iron deficiency anemia. The present article discusses the role of iron cookware in treating and preventing iron deficiency anemia, the necessary cautions when doing so, recommendations and counterindications. The scientific literature was thoroughly reviewed in order to provide backup to professionals who work in the public health care system, showing the peculiar characteristics of iron pans and showing how they can help eradicate iron deficiency anemia efficiently.