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Maternal severe zinc (Zn) deficiency resulted in growth retardation and high mortality during embryonic development in human. Therefore, this study is aimed at evaluating the effect of maternal marginal Zn deficiency on the development and redox status to avoid severe Zn deficiency using an avian model. A total of 324 laying duck breeders at 214 days old were randomly allotted into 3 dietary Zn levels with 6 replicates of 18 ducks per replicate. The birds were fed experimental diets including 3 dietary supplemental Zn levels of 0 mg/kg (maternal Zn-deficient group, 29.2 mg Zn/kg diet), 60 mg/kg (maternal Zn-adequate group), and 120 mg/kg (maternal Zn-high group) for 6 weeks. Dietary Zn levels had on effect on egg production and fertility ( P > 0.05 ), whereas dietary Zn deficiency decreased breeder plasma Zn concentration and erythrocytic alkaline phosphatase activity at week 6 and inhibited erythrocytic 5 ′ -nucleotidase (5 ′ -NT) activity at weeks 2, 4, and 6 ( P < 0.05 ), indicating that marginal Zn-deficient status occurred after Zn depletion. Maternal marginal Zn deficiency increased embryonic mortality and contents of superoxide anion radical, MDA, and PPC and reduced MT content and CuZnSOD activity in duck embryonic livers on E29. The MDA content was positively correlated with embryonic mortality. Maternal marginal Zn deficiency increased BCL2-associated X protein and Caspase-9 mRNA expressions as well as decreased B-cell lymphoma-2 and MT1 mRNA and signal AKT1 and ERK1 protein expressions ( P < 0.05 ). Breeder plasma Zn concentration and erythrocytic 5 ′ -NT activities at week 6 were positively correlated with GSH-Px activity and GPx, MT1, and BCL2 mRNA expressions in embryonic livers on E29. In conclusion, erythrocytic 5 ′ -NT activity could be more rapid and reliable to monitor marginal Zn-deficient status. Marginal Zn deficiency impaired hatchability and antioxidant defense system and then induced oxidative damage and apoptosis in the embryonic liver, contributing to the greater loss of duck embryonic death.

Dry skin is a common symptom of various conditions, and elderly individuals commonly exhibit this physiological symptom. Dry skin develops owing to sebum deficiency; however, the use of moisturizers can typically overcome this issue, particularly in patients in whom there are no other skin problems. If dry skin is left untreated, itching and eczema can occur, resulting in skin damage. Additionally, hemodialysis patients exhibit reduced barrier function and can experience pain associated with repeated needle insertion; the repeated use of lidocaine tape to manage the pain can cause further skin damage. To reduce the occurrence of dry skin, the skin is hydrated using moisturizers. Dry skin is also prominent in patients with varicose veins in the lower extremities, and many biochemical studies have shown that skin immunity is altered in patients with dry skin. Moreover, the incidences of dry skin and pruritus differ in male and female patients. Furthermore, in elderly patients, zinc deficiency is likely to cause dry skin, and zinc supplementation may maintain skin hydration. To date, few reports have described dry skin from a clinical point of view. In this review, research on dry skin is presented, and the findings of basic research studies are integrated.

Objective: Placental iodide transport is necessary for maintaining an adequate iodide supply to the developing fetus. We hypothesized that compounds from the placental barrier can compensate for de...

Summary Zinc deficiency has a global impact on health in both developing and developed countries, especially among children and the elderly. By modulating anti-inflammatory and antioxidant pathways, zinc supplementation is recommended for the treatment of several ailments, such as liver disease, male hypogonadism, cancers, heart disease (e.g. dyslipidemia) and central nervous system disorders; however, the topic of dietary vs. pharmacological doses of zinc remains controversial. This paper provides a detailed critical review of the effects of zinc supplementation in medicinal doses (i.e. >40 mg/d of elemental zinc) on human health. We further highlight the difficulty in achieving a therapeutic dose of zinc from foodstuffs.

Stress is the nonspecific response of the body to any demand for change. Excess or chronic psychological or environmental stress is associated with an increased risk of mental and physical diseases, with several mechanisms theorized to be associated with its detrimental effects. One underappreciated potential mechanism relates to the effects of psychological and environmental stress on micronutrient concentrations. Micronutrients (vitamins and minerals) are essential for optimal physical and mental function, with deficiencies associated with an array of diseases. In this article, animal and human studies investigating the effects of various psychological and environmental stressors on micronutrient concentrations are reviewed. In particular, the effects of psychological stress, sleep deprivation, and physical exercise on micronutrient concentrations and micronutrient excretion are summarized. Micronutrients identified in this review include magnesium, zinc, calcium, iron, and niacin. Overall, the bulk of evidence suggests stress can affect micronutrient concentrations, often leading to micronutrient depletion. However, before definitive conclusions about the effects of stress can be made, the impact of different stressors, stress severity, and acute versus chronic stress on micronutrient concentrations requires investigation. Moreover, the impact of stress on micronutrients in different populations varying in age, gender, and premorbid health status and the durability of changes after a stressor is resolved require examination. The medical, physical, and psychological implications of nutrient changes caused by a stressor also remain to be determined.

Chronic arsenic exposure via drinking water is associated with diabetes in human pop-ulations throughout the world. Arsenic is believed to exert its diabetogenic effects via multiple mechanisms, including alterations to insulin secretion and insulin sensitivity. In the past, acute arsenicosis has been thought to be partially treatable with selenium supplementation, though a potential interaction between selenium and arsenic had not been evaluated under longer-term exposure models. The purpose of the present study was to explore whether selenium status may augment arsenic’s effects during chronic arsenic exposure. To test this possibility, mice were exposed to arsenic in their drinking water and provided ad libitum access to either a diet replete with selenium (Control) or deficient in selenium (SelD). Arsenic significantly improved glucose tolerance and decreased insulin secretion and β-cell function in vivo. Dietary selenium deficiency resulted in similar effects on glucose tolerance and insulin secretion, with significant interactions between arsenic and dietary conditions in select insulin-related parameters. The findings of this study highlight the complexity of arsenic’s metabolic effects and suggest that selenium deficiency may interact with arsenic exposure on β-cell-related physiological parameters.

Vitamin D receptor (VDR) deficiency is associated with cancer, infection, and chronic inflammation. Prior research has demonstrated VDR regulation of bacteria; however, little is known regarding VDR and viruses. We hypothesize that VDR deficiency impacts on the intestinal virome and viral-bacterial interactions. We specifically deleted VDR from intestinal epithelial cells (VDRΔIEC), Paneth cells (VDRΔPC), and myeloid cells (VDRΔLyz) in mice. Feces were collected for shotgun metagenomic sequencing and metabolite profiling. To test the functional changes, we evaluated pattern recognition receptors (PRRs) and analyzed microbial metabolites. Vibrio phages, Lactobacillus phages, and Escherichia coli typing phages were significantly enriched in all three conditional VDR-knockout mice. In the VDRΔLyz mice, the levels of eight more virus species (2 enriched, 6 depleted) were significantly changed. Altered virus species were primarily observed in female VDRΔLyz (2 enriched, 3 depleted) versus male VDRΔLyz (1 enriched, 1 depleted). Altered alpha and beta diversity (family to species) were found in VDRΔLyz. In VDRΔIEC mice, bovine viral diarrhea virus 1 was significantly enriched. A significant correlation between viral and bacterial alterations was found in conditional VDR knockout mice. There was a positive correlation between Vibrio phage JSF5 and Cutibacterium acnes in VDRΔPC and VDRΔLyz mice. Also, there were more altered viral species in female conditional VDR knockout mice. Notably, there were significant changes in PRRs: upregulated TLR3, TLR7, and NOD2 in VDRΔLyz mice and increased CLEC4L expression in VDRΔIEC and VDRΔPC mice. Furthermore, we identified metabolites related to virus infection: decreased glucose in VDRΔIEC mice, increased ribulose/xylulose and xylose in VDRΔLyz mice, and increased long-chain fatty acids in VDRΔIEC and VDRΔLyz female mice. Tissue-specific deletion of VDR changes the virome and functionally changes viral receptors, which leads to dysbiosis, metabolic dysfunction, and infection risk. This study helps to elucidate VDR regulating the virome in a tissue-specific and sex-specific manner.

The influence of dietary nutrient intake on the onset and trajectory of hearing loss during aging and in mediating protection from challenges such as noise is an important relationship yet to be fully appreciated. Dietary intake provides essential nutrients that support basic cellular processes related to influencing cellular stress response, immune response, cardiometabolic status, neural status, and psychological well-being. Dietary quality has been shown to alter risk for essentially all chronic health conditions including hearing loss and tinnitus. Evidence of nutrients with antioxidant, anti-inflammatory, and anti-ischemic properties, and overall healthy diet quality as otoprotective strategies are slowly accumulating, but many questions remain unanswered. In this article, the authors will discuss (1) animal models in nutritional research, (2) evidence of dietary nutrient-based otoprotection, and (3) consideration of confounds and limitations to nutrient and dietary study in hearing sciences. Given that there are some 60 physiologically essential nutrients, unraveling the intricate biochemistry and multitude of interactions among nutrients may ultimately prove infeasible; however, the wealth of available data suggesting healthy nutrient intake to be associated with improved hearing outcomes suggests the development of evidence-based guidance regarding diets that support healthy hearing may not require precise understanding of all possible interactions among variables. Clinical trials evaluating otoprotective benefits of nutrients should account for dietary quality, noise exposure history, and exercise habits as potential covariates that may influence the efficacy and effectiveness of test agents; pharmacokinetic measures are also encouraged.

Meta-analytic evidence indicates that mood and psychotic disorders are associated with both omega-3 polyunsaturated fatty acid (omega-3 PUFA) deficits and progressive regional gray and white matter pathology. Although the association between omega-3 PUFA insufficiency and progressive neuropathological processes remains speculative, evidence from translational research suggests that omega-3 PUFA insufficiency may represent a plausible and modifiable risk factor not only for enduring neurodevelopmental abnormalities in brain structure and function, but also for increased vulnerability to neurodegenerative processes. Recent evidence from human neuroimaging studies suggests that lower omega-3 PUFA intake/status is associated with accelerated gray matter atrophy in healthy middle-aged and elderly adults, particularly in brain regions consistently implicated in mood and psychotic disorders, including the amygdala, anterior cingulate, hippocampus, prefrontal cortex, and temporal cortex. Human neuroimaging evidence also suggests that both low omega-3 PUFA intake/status and psychiatric disorders are associated with reductions in white matter microstructural integrity and increased rates of white matter hyperintensities. Preliminary evidence suggests that increasing omega-3 PUFA status is protective against gray matter atrophy and deficits in white matter microstructural integrity in patients with mood and psychotic disorders. Plausible mechanisms mediating this relationship include elevated pro-inflammatory signaling, increased synaptic regression, and reductions in cerebral perfusion. Together these associations encourage additional neuroimaging research to directly investigate whether increasing omega-3 PUFA status can mitigate neuropathological processes in patients with, or at high risk for, psychiatric disorders.

International audience; Objective: Dietary intakes must cover protein and essential amino acid (EAA) requirements. For this purpose, different methods have been developed such as the nitrogen balance method, factorial method, or AA tracer studies. However, these methods are either invasive or imprecise, and the Food and Agriculture Organization of the United Nations (FAO, 2013) recommends new methods and, in particular, metabolomics. The aim of this study is to determine total protein/EAA requirement in the plasma and urine of growing rats. Methods: 36 weanling rats were fed with diets containing 3, 5, 8, 12, 15, and 20% protein for 3 weeks. During experimentation, urine was collected using metabolic cages, and blood from the portal vein and vena was taken at the end of the experiment. Metabolomics analyses were performed using LC-MS, and the data were analyzed with a multivariate analysis model, partial least Squares (PLS) regression, and independent component-discriminant analysis (ICDA). Each discriminant metabolite identified by PLS or ICDA was tested by one-way ANOVA to evaluate the effect of diet. Results: PLS and ICDA allowed us to identify discriminating metabolites between different diet groups. Protein deficiency led to an increase in the AA catabolism enzyme systems inducing the production of breakdown metabolites in the plasma and urine. Conclusion: These results indicate that metabolites are specific for the state of EAA deficiency and sufficiency. Some types of biomarkers such as AA degradation metabolites appear to be specific candidates for protein/EAA requirement.

Micronutrient deficiencies are relatively common, in particular iron and cobalamin deficiency, and may potentially lead to life-threatening clinical consequences when not promptly recognized and treated, especially in elderly patients. The stomach plays an important role in the homeostasis of some important hematopoietic micronutrients like iron and cobalamin, and probably in others equally important such as ascorbic acid, calcium, and magnesium. A key role is played by the corpus oxyntic mucosa composed of parietal cells whose main function is gastric acid secretion and intrinsic factor production. Gastric acid secretion is necessary for the digestion and absorption of cobalamin and the absorption of iron, calcium, and probably magnesium, and is also essential for the absorption, secretion, and activation of ascorbic acid. Several pathological conditions such as Helicobacter pylori-related gastritis, corpus atrophic gastritis, as well as antisecretory drugs, and gastric surgery may interfere with the normal functioning of gastric oxyntic mucosa and micronutrients homeostasis. Investigation of the stomach by gastroscopy plus biopsies should always be considered in the management of patients with micronutrient deficiencies. The current review focuses on the physiological and pathophysiological aspects of gastric acid secretion and the role of the stomach in iron, cobalamin, calcium, and magnesium deficiency and ascorbate homeostasis.

Zinc (Zn) is the second most abundant necessary trace element in the human body. It is reported that zinc deficiency (ZD) promotes many types of cancer progression through multiple signal pathways. It is well known that oxidative stress, DNA damage, DNA repair, cell cycle, cell apoptosis, metabolic alterations, microRNAs abnormal expression, and inflammation level are closely related to cancer development. Cumulative evidence suggests that ZD influences these biological functions. This review explores the latest advances in understanding the role of ZD in tumorigenesis. Fully comprehending the potential mechanisms of ZD-induced tumors may provide novel clues for prevention and clinical treatment of cancers.

Lysine cannot be synthesized by most higher organisms and, therefore, is an indispensable amino acid (IAA) that must be consumed in adequate amounts to maintain protein synthesis. Although lysine is an abundant amino acid in body proteins, lysine is limited in abundance in many important food sources (e.g. grains). Older observations assigned importance to lysine because animals fed a lysine-deficient diet did not lose weight as fast as animals placed upon other IAA-deficient diets, leading to the theory that there may be a special pool of lysine or metabolites that could be converted to lysine. The first step in the lysine catabolic pathway is the formation of saccharopine and then 2-aminoadipic acid, processes that are mitochondrial. The catabolism of 2-aminoadipic acid proceeds via decarboxylation to a series of CoA esters ending in acetyl-CoA. In mammals, the liver appears to be the primary site of lysine catabolism. In humans, the metabolic and oxidative response of lysine to diets either restricted in protein or in lysine is consistent with what has been measured for other IAAs with isotopically labeled tracers. Intestinal microflora are known to metabolize urea to ammonia and scavenge nitrogen (N) for the synthesis of amino acids. Studies feeding 15N-ammonium chloride or 15N-urea to animals and to humans, demonstrate the appearance of 15N-lysine in gut microbial lysine and in host lysine. However, the amount of 15N-lysine transferred to the host is difficult to assess directly using current methods. It is important to understand the role of the gut microflora in human lysine metabolism, especially in conditions where dietary lysine intake may be limited, but better methods need to be devised.

Pulmonary arterial hypertension (PAH) is characterized by sustained vasoconstriction, vascular remodeling, inflammation, and in situ thrombosis. Although there have been important advances in the knowledge of the pathophysiology of PAH, it remains a debilitating, limiting, and rapidly progressive disease. Vitamin D and iron deficiency are worldwide health problems of pandemic proportions. Notably, these nutritional alterations are largely more prevalent in PAH patients than in the general population and there are several pieces of evidence suggesting that they may trigger or aggravate disease progression. There are also several case reports associating scurvy, due to severe vitamin C deficiency, with PAH. Flavonoids such as quercetin, isoflavonoids such as genistein, and other dietary polyphenols including resveratrol slow the progression of the disease in animal models of PAH. Finally, the role of the gut microbiota and its interplay with the diet, host immune system, and energy metabolism is emerging in multiple cardiovascular diseases. The alteration of the gut microbiota has also been reported in animal models of PAH. It is thus possible that in the near future interventions targeting the nutritional status and the gut dysbiosis will improve the outcome of these patients., This study was supported by grants from Mineco (SAF2016-77222-R and SAF2017-8489-R), with funds from the European Union (Fondo Europeo de Desarrollo Regional FEDER) and Fundación Contra la Hipertensión Pulmonar (Empathy grant).

Objectives Distinct diseases prevent endangered huemul deer (Hippocamelus bisulcus) recovery. Fundamental etiological factors include nutriments, a mayor component of habitat quality. Undernutrition affects growth, skeletal development, osteopathology, reproduction and immunocompetence: this paper amplifies data corroborating micro-nutrient deficiencies among huemul. Results In Argentina, 57% huemul cadavers exhibited osteopathology, with new cases reported here. Recently, 86% live huemul had osteopathology: cranial lesions involved antemortem tooth loss, reducing feeding efficiency and body condition, with starvation deaths. This population had tissues well deficient compared to other cervids, averaging 0.28 ppm selenium, 4.98 ppm copper, whereas for manganese 55% were deficient (2.52 ppm) and 45% adequate (42.79 ppm). Recently, lesions in one Chilean huemul were interpreted to stem from parapoxvirus. That population also has cases with cranial osteopathologies, high disease susceptibility (parapoxvirus, parasitism, foot lesions), crippled antlers, and low density, indicative of marginal habitat and primary etiological factors like undernutrition and immunosuppression. The reported atypical symptoms attributed to parapoxvirus may relate to probable diagnostic limitations, but does support presence of nutritional deficiencies. Patagonia has selenium deficient plants and livestock, including severe muscular dystrophy, and soil levels in extant huemul areas considered very deficient. Moreover, 73% of Chilean huemul were selenium deficient and 64% severely deficient with concomitant cranial osteopathology.

Owing to the use of ethyl tert-butyl ether (ETBE) as a fuel additive, the possible adverse effects of ETBE exposure have become a public concern. Our previous study showed that ETBE-induced toxicity in aldehyde dehydrogenase 2 (Aldh2) gene knockout (KO) mice was caused by its primary metabolite acetaldehyde, which was toxic. However, it is unclear whether tert-butyl alcohol (TBA), another main metabolite of ETBE, plays a role in ETBE-induced toxicity. To investigate this relationship, we analyzed the changes of TBA concentrations in tissues after ETBE exposure, and then evaluated the toxicity after direct TBA treatment in both KO and wild-type (WT) mice. An exposure to 500 ppm ETBE via inhalation resulted in the formation of its three metabolites, TBA, 2-methyl-1,2-propanediol and ethanol, whose concentrations in the liver, brain, fat and testis of male KO mice were significantly higher than the corresponding concentrations observed in male WT mice. Direct treatment to TBA (20 mg/mL of drinking water) caused significant changes in relative organ weights and histopathology, and increased levels of genetic damages in both types of mice. These toxic effects were also seen in KO mice exposed to a lower concentration of TBA (5 mg/mL), which was associated with increased oxidative stress in serum (reduced glutathione and reduced glutathione/oxidized glutathione ratio decreased). Our findings indicate that ALDH2 is involved in the metabolism of ETBE and TBA, and ALDH2 deficiency could greatly increase the sensitivity to TBA-induced toxicity.

Objectives In diabetes, oxidative stress and lipid abnormalities are common and pronounced and represent important factors that are involved in the development of complications of diabetes. Zinc deficiency generally induces oxidative stress, but it is well known that the antioxidant Ruta chalepensis has an effective modulator role in oxidative stress in metabolic diseases. The aim of this study was to investigate the effect of R. chalepensis extract on blood biochemical parameters, tissue zinc status and antioxidant systems in rats with diabetes that were fed zinc-deficient diets. Methods We divided 28 male albino Wistar rats into 4 groups: 2 groups (1 group with diabetes, 1 group without diabetes) were fed zinc-sufficient diets, while the other 2 groups of rats with diabetes were fed zinc-deficient diets. One group was not treated, and the other was treated with the extract of R. chalepensis. After 3 weeks of dietary manipulation, the fasting animals were killed. Results The body-weight gains of the zinc-deficient animals with diabetes were lower than those of the zinc-adequate animals with diabetes. It was noticed also that inadequate dietary zinc intake increased the glucose, cholesterol, triglyceride, urea, uric acid, creatinine and lipid peroxidation levels. In addition, the zinc-deficient diet led to a decrease in zinc tissues (femur, liver, kidney), glutathione concentration and both glutathione peroxidase and glutathione-S-transferase activities. However, R. chalepensis treatment ameliorated all the previous parameters approximately to their normal levels. Conclusions It seems that R. chalepensis supplementation is a potent factor in reducing the oxidative severity of zinc deficiency in experimental diabetes through its hypoglycemic and antioxidant actions.

Dietary iodine requirements are high during pregnancy, lactation, and infancy, making women and infants vulnerable to iodine deficiency. Universal salt iodization (USI) has been remarkably successful for preventing iodine deficiency in the general population, but it is uncertain if USI provides adequate iodine intakes during the first 1000 d.We set out to assess if USI provides sufficient dietary iodine to meet the iodine requirements and achieve adequate iodine nutrition in all vulnerable population groups.We conducted an international, cross-sectional, multicenter study in 3 study sites with mandatory USI legislation. We enrolled 5860 participants from 6 population groups (school-age children, nonpregnant nonlactating women of reproductive age, pregnant women, lactating women, 0-6-mo-old infants, and 7-24-mo-old infants) and assessed iodine status [urinary iodine concentration (UIC)] and thyroid function in Linfen, China (n = 2408), Tuguegarao, the Philippines (n = 2512), and Zagreb, Croatia (n = 940). We analyzed the iodine concentration in household salt, breast milk, drinking water, and cow's milk.The salt iodine concentration was low (15 mg/kg) in 2.7%, 33.6%, and 3.1%, adequate (15-40 mg/kg) in 96.3%, 48.4%, and 96.4%, and high (40 mg/kg) in 1.0%, 18.0%, and 0.5% of household salt samples in Linfen (n = 402), Tuguegarao (n = 1003), and Zagreb (n = 195), respectively. The median UIC showed adequate iodine nutrition in all population groups, except for excessive iodine intake in school-age children in the Philippines and borderline low intake in pregnant women in Croatia.Salt iodization at ∼25 mg/kg that covers a high proportion of the total amount of salt consumed supplies sufficient dietary iodine to ensure adequate iodine nutrition in all population groups, although intakes may be borderline low during pregnancy. Large variations in salt iodine concentrations increase the risk for both low and high iodine intakes. Strict monitoring of the national salt iodization program is therefore essential for optimal iodine nutrition. This trial was registered at clinicaltrials.gov as NCT02196337.

Background Low protein amounts are used in ketogenic diets (KDs), where an essential (indispensable) amino acid (IAA) can become limiting. Because the chemically sensitive, seizurogenic, anterior piriform cortex (APC) is excited by IAA limitation, an imbalanced KD could exacerbate seizure activity. Objective We questioned whether dietary IAA depletion worsens seizure activity in rodents fed KDs. Methods In a series of 6 trials, male rats or gerbils of both sexes (6-8/group) were given either control diets (CDs) appropriate for each trial, a KD, or a threonine-devoid (ThrDev) diet for ≥7 d, and tested for seizures using various stimuli. Microchip analysis of rat APCs was also used to determine if changes in transcripts for structures relevant to seizurogenesis are affected by a ThrDev diet. Glutamate release was measured in microdialysis samples from APCs during the first meal after 7 d on a CD or a ThrDev diet. Results Adult rats showed increased susceptibility to seizures in both chemical (58%) and electroshock (doubled) testing after 7 d on a ThrDev diet compared with CD (each trial, P ≤ 0.05). Seizure-prone Mongolian gerbils had fewer seizures after receiving a KD, but exacerbated seizures (68%) after 1 meal of KD minus Thr (KD-T compared with CD, P

The impact of environmental pollution, especially chronic low exposures of heavy metals (Pb, Cd, Hg, As, Cr, etc.) on nutritional status and health of human and livestock, has become a cause of concern. It is established that malnutrition inhibits enzyme system, alters neurotransmitter levels, degenerate myelin, glial and neural elements, lowering of IQ scores as well as impairment of fine and gross motor coordination. Chronic low-level exposure to heavy metals also results in similar type of deformities at sub-clinical level. However, additive impact of undernutrition and adverse effects of heavy metal exposure is emerging as a serious threat to health in developing countries. High blood Pb/Cd levels and low nutrient levels cause subclinical damage of organ system such as haemopoietic, renal, nervous systems in neonates, children, post-partum women, and occupationally exposed population. This could be due to chronic low-level heavy metal exposures and vis-à-vis interaction between pollutants and nutrients. Our studies are focused on the utility of biomarkers for early subclinical detection of haemopoietic and rental toxicity. Lead exposure from non-conventional sources such as toys, pet/glass bottles, etc. suggest long-term investigation. The present review compiles result of studies conducted in this area highlighting the importance of pollution-nutrition interaction. This may facilitate policymakers on developing the strategies to counter the heavy metal exposure of humans/livestock and their consequences.

Background: Premature infants are deprived of prenatal accumulation of brain docosahexaenoic acid [DHA (22:6n-3)], an omega-3 fatty acid [ω-3 FA (n-3 FA)] important for proper development of cognitive function. The resulting brain DHA deficit can be reversed by ω-3 FA supplementation.Objective: The objective was to test whether there is a critical period for providing ω-3 FA to correct cognitive deficits caused by developmental ω-3 FA deprivation in mice.Methods: Twelve timed-pregnant mice [embryonic day 14 (E14), C57/BL6NCr] were fed an ω-3 FA-deficient diet containing 0.04% α-linolenic acid [ALA (18:3n-3)], and their offspring were fed the same deficient diet (Def group) or changed to an ω-3 FA-adequate diet containing 3.1% ALA at 3 wk, 2 mo, or 4 mo of age. In parallel, 3 E14 pregnant mice were fed the adequate diet and their offspring were fed the same diet (Adeq group) throughout the experiment. Brain FA composition, learning and memory, and hippocampal synaptic protein expression were evaluated at 6 mo by gas chromatography, the Morris water maze test, and western blot analysis, respectively.Results: Maternal dietary ω-3 FA deprivation decreased DHA by >50% in the brain of their offspring at 3 wk of age. The Def group showed significantly worse learning and memory at 6 mo than those groups fed the adequate diet. These pups also had decreased hippocampal expression of postsynaptic density protein 95 (43% of Adeq group), Homer protein homolog 1 (21% of Adeq group), and synaptosome-associated protein of 25 kDa (64% of Adeq group). Changing mice to the adequate diet at 3 wk, 2 mo, or 4 mo of age restored brain DHA to the age-matched adequate concentration. However, deficits in hippocampal synaptic protein expression and spatial learning and memory were normalized only when the diet was changed at 3 wk.Conclusion: Developmental deprivation of brain DHA by dietary ω-3 FA depletion in mice may have a lasting impact on cognitive function if not corrected at an early age.

Background IL36RN encodes the IL-36 receptor antagonist (IL-36Ra), and loss-of-function mutations in IL36RN define a recessively inherited autoinflammatory disease named “deficiency of IL-36Ra” (DITRA). DITRA causes systemic autoinflammatory diseases, including generalized pustular psoriasis (GPP), an occasionally life-threatening disease that is characterized by widespread sterile pustules on the skin, fever and other systemic symptoms. GPP can present at any age, and provocative factors include various infections, medicines and pregnancy. Objective We aimed to elucidate the role of toll-like receptor 4 (TLR4) signaling in DITRA and to innovate an efficient treatment for DITRA. Methods We generated Il36rn−/− mice and treated them with TLR4 agonist to establish DITRA model mice. Furthermore, we administrated TLR4 antagonist TAK-242 to the model mice to inhibit the DITRA symptoms. Result Il36rn−/− mice treated by TLR4 agonist showed autoinflammatory symptoms in skin, articulation and liver. Thus, we established model mice for DITRA or GPP that show cutaneous, articular, and hepatic autoinflammatory symptoms typical of DITRA or GPP: sterile pustules on the skin, liver abscesses and enthesitis of the hind paws. Additionally, these symptoms were canceled by TAK-242 administration. We demonstrated the inhibitory effects of the TLR4 antagonist TAK-242 on the autoinflammatory symptoms exhibited by the DITRA models. Conclusion We suggested that blockage of TLR4 signaling is a promising treatment for DITRA and GPP.

Background:Vitamin D can be one of the candidate substances that are used as additional supplementation in the treatment of anxiety-related disorders in women with estrogen imbalance.Materials and methods:The aim of the present study was to examine the effects of chronic cholecalciferol administration (1.0, 2.5 or 5.0 mg/kg/day, s.c.) on the anxiety-like behavior and monoamines levels in the rat hippocampus following ovariectomy in female rats. Cholecalciferol was given to ovariectomized (OVX) rats and OVX rats treated with 17β-estradiol (17β-E2, 0.5 μg/rat, s.c.). The anxiety-like behavior was assessed in the elevated plus maze (EPM) and the light-dark tests (LDT), locomotor and grooming activities were assessed in the open-field test (OFT).Results:Cholecalciferol in high doses alone or in combination with 17β-E2-induced anxiolytic-like effects in OVX and OVX rats treated with 17β-E2as evidenced in the EPM and LDT tests, and increased grooming activity in the OFT test. We found that DA and 5-HT levels increased while 5-HT turnover in the hippocampus decreased in these groups of OVX rats.Conclusion:Our results indicate that cholecalciferol in high doses has a marked anxiolytic-like effect due to an increase in the monoamines levels in the experimental rat model of estrogen deficiency.

Dietary guidelines in many countries include a recommendation to consume oily fish, mainly on the basis of evidence from prospective cohort studies that fish consumption is cardioprotective. However, average intakes are very low in a large proportion of the UK population. Some groups, such as vegans and vegetarians, purposely omit fish (along with meat) from their diet resulting in zero or trace intakes of long chain (LC) n-3 PUFA. Although the efficacy of dietary fish oil supplementation in the prevention of CVD has been questioned in recent years, the balance of evidence indicates that LC n-3 PUFA exert systemic pleiotropic effects through their influence on gene expression, cell signalling, membrane fluidity and by conversion to specialised proresolving mediators; autacoid lipid mediators that resolve inflammatory events. The long-term impact of reduced tissue LC n-3 PUFA content on cardiovascular health is surprisingly poorly understood, particularly with regard to how low proportions of LC n-3 PUFA in cell membranes may affect cardiac electrophysiology and chronic inflammation. Randomised controlled trials investigating effects of supplementation on prevention of CHD in populations with low basal LC n-3 PUFA tissue status are lacking, and so the clinical benefits of supplementing non-fish-eating groups with vegetarian sources of LC n-3 PUFA remain to be determined. Refocusing dietary LC n-3 PUFA intervention studies towards those individuals with a low LC n-3 PUFA tissue status may go some way towards reconciling results from randomised controlled trials with the epidemiological evidence.

4-tert-octylphenol (OP) is an endocrine-disrupting chemical that causes harmful effects to human health. Chlorogenic acid is the major dietary polyphenol present in various foods and beverages. The aim of the present study was to evaluate the protective role of chlorogenic acid in anemia and mineral disturbance occurring in OP toxicity in rats. Thirty-two male albino rats were divided into four equal groups (8 rats/group) as follows. The first (control) group was treated daily with an oral dose of 1 ml saline for two weeks. The second group was treated daily with an oral dose of 60 mg chlorogenic acid/kg body weight for two weeks. The third and fourth groups received daily intraperitoneal (ip) injections with 100 mg OP/kg body weight for two weeks; the fourth group was treated daily with an oral dose of 60 mg chlorogenic acid/kg body weight for three weeks starting one week before OP injections. The results revealed that OP induced significant decreases in hemoglobin, hematocrit, red blood cells, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration, platelet count, white blood cells, lymphocyte and neutrophil percent, transferrin receptor, serum calcium, phosphorous, sodium, potassium, chloride, glutathione-S-transferase, glutathione peroxidase, catalase, glutathione reductase, and superoxide dismutase. Moreover, significant increases in serum hepcidin, ferritin, transferrin, erythropoietin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, creatinine, selenium, zinc, manganese, copper, iron, malondialdehyde, and protein carbonyl levels were found in OP groups. OP exposure also induced cell apoptosis. Chlorogenic acid pretreatment in OP-treated groups restored all the mentioned parameters to approach the normal values. In conclusion, chlorogenic acid protects from anemia and mineral disturbances in 4-tert-octylphenol toxicity by ameliorating oxidative stress and apoptosis.

Background: Subclinical zinc deficiency (SZD) represents the common zinc malnutrition phenotype. However, its association with oxidative stress is not well understood. The heart muscle may be a promising target for studying early changes in redox metabolism.Objective: We investigated the effects of short-term SZD on cardiac redox metabolism in weaned piglets.Methods: Forty-eight weaned German Large White × Landrace × Pietrain piglets (50% castrated males and 50% females; body weight of 8.5 kg) were fed diets with different zinc concentrations for 8 d. Measurements included cardiac parameters of antioxidative capacity, stress-associated gene expression, and tissue zinc status. Analyses comprised (linear, broken-line) regression models and Pearson correlation coefficients.Results: Glutathione and α-tocopherol concentrations as well as catalase, glutathione reductase, B-cell lymphoma 2-associated X protein, and caspase 9 gene expression plateaued in response to reduction in dietary zinc from 88.0 to 57.6, 36.0, 36.5, 41.3, 55.3, and 33.8 mg/kg, respectively (P < 0.0001). Further reduction in dietary zinc promoted a linear decrease of glutathione and α-tocopherol (30 and 0.6 nmol/mg dietary Zn, respectively; P < 0.05) and a linear increase of gene expression [0.02, 0.01, 0.003, and 0.02 Log10(2-ΔΔCt)/mg dietary Zn, respectively; P < 0.05)]. Tissue zinc declined linearly with reduction in dietary zinc (0.21 mg tissue Zn/mg dietary Zn; P = 0.004) from 88.0 to 42.7 mg/kg (P < 0.0001), below which it linearly increased inversely to further reduction in dietary zinc (0.57 mg tissue Zn/mg dietary Zn; P = 0.006). H2O2-detoxification activity and metallothionein 1A gene expression decreased linearly with reduction in dietary zinc from 88.0 to 28.1 mg/kg [0.02 mU and 0.008 Log10(2-ΔΔCt)/mg dietary Zn, respectively; P < 0.05]. Fas cell-surface death receptor, etoposide-induced 2.4 and cyclin-dependent kinase inhibitor 1A gene expression correlated positively to cardiac zinc in piglets fed ≤42.7 mg Zn/kg (r ≥ 0.97; P < 0.05).Conclusions: Short-term SZD decreased cardiac antioxidative capacity of weaned piglets while simultaneously increasing stress-associated gene expression and zinc concentration. This is the first report to our knowledge on the effects of SZD on redox metabolism.

Background and Aims Patients with inflammatory bowel disease [IBD], especially Crohn’s disease, often develop zinc deficiency. However, the precise mechanisms by which zinc deficiency affects IBD pathology, particularly intestinal macrophage function, remain unclear. We studied the effects of zinc deficiency on the development and progression of colitis in mice. Methods To induce colitis, mice were treated with 2,4,6-trinitrobenzene sulphonic acid. Rag1−/− mice were then given injections of naïve CD4+CD62L+ T cells. The respective degrees of mucosal injury of mice that had received a zinc chelator (TPEN; N,N,N′,N′-tetrakis [2-pyridylmethyl]ethylenediamine) and of control mice were subsequently compared. Colonic lamina propria mononuclear cells were isolated by enzymatic digestion and were examined using flow cytometry. To generate mouse bone marrow-derived macrophages [BMDMs], bone marrow cells were stimulated with mouse macrophage-colony stimulating factor. Results Zinc deficiency aggravates colonic inflammation through the activation of type 17 helper T [Th17] cells in mice. Flow cytometric analysis revealed that zinc deficiency significantly increases the proportion of pro-inflammatory [M1] macrophages in colonic lamina propria mononuclear cells obtained from inflamed colon. Interferon-γ plus lipopolysaccharide-mediated M1 skewing alters the expression of zinc transporters in BMDMs and thereby decreases the intracellular free zinc. TPEN treatment mimicking the effects of the M1 skewing up-regulates IL-23p19 expression, which is strongly related to Th17 development. Furthermore, the nuclear accumulation of interferon-regulatory factor 5 is closely involved in IL-23p19 induction in zinc-deficient macrophages. Conclusions Zinc deficiency aggravates colonic inflammation through activation of the IL-23/Th17 axis. This activation is controlled by subcellular distribution of interferon-regulatory factor 5.

Deficiencies in methyl donors, folate, and vitamin B12 are known to lead to brain function defects. Fetal development is the most studied but data are also available for such an impact in elderly rats. To compare the functional consequences of nutritional deficiency in young versus adult rats, we monitored behavioral outcomes of cerebellum and hippocampus circuits in the offspring of deficient mother rats and in adult rats fed a deficient diet from 2 to 8 months-of-age. We present data showing that the main deleterious consequences are found in young ages compared to adult ones, in terms of movement coordination and learning abilities. Moreover, we obtained sex and age differences in the deleterious effects on these functions and on neuronal layer integrity in growing young rats, while deficient adults presented only slight functional alterations without tissue damage. Actually, the cerebellum and the hippocampus develop and maturate according to different time lap windows and we demonstrate that a switch to a normal diet can only rescue circuits that present a long permissive window of time, such as the cerebellum, whereas the hippocampus does not. Thus, we argue, as others have, for supplements or fortifications given over a longer time than the developmental period.

Species differences in calcium and phosphorus metabolism can be expressed via dietary and faecal calcium/phosphorus ratios. The aim of the present meta-analysis was to use faecal Ca/P ratios as an indicator of phosphorus digestibility in growing pigs as a simple diagnostic tool. This tool can be useful in cases of suspected phosphorus deficiency but adequate dietary calcium and phosphorus contents.Studies (n = 34) with phytase-supplemented (PHYT; n = 110) and non-supplemented control (CON; n = 106) diets were analysed for dietary intake, faecal excretion and apparent digestibility of calcium and phosphorus. A modified Lucas-test was used for both minerals plotting intake against faecal excretion (mg/kg body weightFor calcium, there was no significant difference between PHYT and CON (p = 0.29) while in accordance with literature, the relative faecal phosphorus excretion was significantly lower in PHYT than CON (p0.01). Faecal calcium/phosphorus ratios were calculated and grouped according to the animals' body weight and apparent phosphorus digestibility (body weight ≤ 30 kg: apparent phosphorus digestibility ≤ 60 % and60 %; body weight30 kg: apparent phosphorus digestibility ≤ 40 % and40 %).Data distribution as displayed in a box plot shows that - given a dietary Ca/P ratio of1.2 - faecal Ca/P ratios of1.5 in pigs with a body weight of ≤ 30 kg and of1.2 in pigs with a body weight of30 kg indicate a high apparent digestibility of phosphorus of60 % and40 %, respectively.When faecal samples reveal a Ca/P ratio above the indicated thresholds, a low phosphorus digestibility is unlikely. No conclusion regarding the apparent phosphorus digestibility can be drawn from faecal Ca/P ratios below this threshold.Speziesunterschiede im Kalzium- und Phosphorstoffwechsel lassen sich quantitativ über die Berechnung der Kalzium/Phosphor-Quotienten in Futter und Kot darstellen. In der vorliegenden Meta-Analyse wurde überprüft, ob auf diese Weise eine Aussage zur Phosphorverdaulichkeit bei wachsenden Schweinen getroffen werden kann, um einen möglichst einfachen Prüfparameter zu definieren. Dies ist in Fällen sinnvoll, in denen trotz adäquater Kalzium- und Phosphorgehalte des Futters der Verdacht auf einen Phosphormangel besteht.Es wurden 34 Studien mit phytasesupplementierten Rationen (PHYT; Datensätze n = 110) und entsprechenden Kontrollrationen (CON; Datensätze n = 106) anhand der Parameter Kalzium- und Phosphoraufnahme, fäkale Kalzium- und Phosphorausscheidung und der jeweiligen scheinbaren Verdaulichkeit ausgewertet. Für beide Mineralien kam ein modifizierter Lucas-Test zur Anwendung, indem eine Regressionsberechnung von fäkaler Ausscheidung gegen Aufnahme (beides in mg/kg KMDer Lucas-Test zeigte keinen signifikanten Unterschied der fäkalen Kalziumausscheidung zwischen PHYT und CON (p = 0,29), während der in der Literatur vielfach beschriebene positive Effekt der Phytase auf die Phosphorverdaulichkeit sehr deutlich wurde (p0,01). Die fäkalen Kalzium/Phosphor-Quotienten aller Datensätze wurden berechnet und gruppiert, und zwar nach der Körpermasse (KM) der Tiere sowie der scheinbaren Phosphorverdaulichkeit (KM ≤ 30 kg: scheinbare Phosphorverdaulichkeit ≤ 60 % und60 %; KM30 kg: scheinbare Phosphorverdaulichkeit ≤ 40 % und40 %).Aus der Datenverteilung im Box Plot kann – unter der Voraussetzung eines Kalzium/Phosphor-Verhältnisses im Futter von ≥ 1,2 – bei einem fäkalen Kalzium/Phosphor-Quotienten von1,5 (für Schweine ≤ 30 kg KM) bzw.1,2 (für Schweine30 kg KM) auf eine hohe scheinbare Phosphorverdaulichkeit von über 60 % bzw. 40 % geschlossen werden.Werden in Kotproben Kalzium/Phosphor-Quotienten über diesen Schwellenwerten erreicht, ist eine schlechte Phosphorverdaulichkeit somit unwahrscheinlich. Bei fäkalen Kalzium/Phosphor-Quotienten unterhalb dieser „Grenzwerte“ ist keine Einschätzung der Phosphorverdaulichkeit möglich.

To analyze the association between supplements and Liconsa milk intake, with anemia, zinc (ZD) and iron (ID) deficiencies, and morbidity in Mexican children resident of less than 100 000 habitants' localities.A subsample of 1 516 children aged 1-4 participants of Ensanut 100k was analyzed, carried out in 2018. Anemia was considered if [Hb]11 g/dL, ZD if [Zn]65 µg/dL and ID if [ferritin]12 µg/L. Supplements and Liconsa milk consumption were obtained from a semi-quantitative food frequency; morbidity by self-report of the mother. Multiple logistic regression models were used adjusted by confounders.Medium and high consumption of Liconsa milk was associated to lower odds of ID (OR=0.02, [95%CI 0.002,0.24] and OR=0.07, [95%CI 0.01,0.52]) and anemia (OR=0.13, [95%CI 0.04,0.37] and OR=0.17, [95%CI 0.03,0.87]). A high intake of Liconsa milk (OR=0.09, [95%CI 0.01,0.44]) and Vitaniño (OR=0.05 [95%CI 0.005, 0.46]) were both associated to lower diarrhea risk.To assure the continuity of the consumption of nutritional supplements is necessary for improving the health and the micronutrients status in vulnerable Mexican children.Analizar la asociación entre el consumo de suplementos o leche Liconsa y anemia, deficiencias de zinc (DZ) y hierro (DH) y morbilidad en niños mexicanos residentes de localidades menores a 100 000 habitantes.Se analizó información de 1 516 niños de 1 a 4 años de la Encuesta Nacional de Salud y Nutrición en localidades con menos de 100 000 habitantes realizada en el año 2018. Se definió Anemia si [Hb]11 g/dL, DZ: [Zn]65 µg/dL y DH: [ferritina]12 µg/L. El consumo de suplementos y de leche Liconsa se obtuvo del cuestionario de Frecuencia de Consumo de Alimentos y morbilidad por autorreporte de la madre. Se emplearon modelos de regresión logística múltiple para el análisis de las asociaciones, ajustados por confusores.El consumo medio y alto de leche Liconsa se asoció con menor momio de DH (RM=0.02 [IC95% 0.002,0.24] y RM=0.07 [IC95% 0.01,0.52]) y anemia (RM=0.13 [IC95% 0.04,0.37] y RM=0.17 [IC95% 0.03,0.87]). Un alto consumo de leche Liconsa (RM=0.09, [IC95% 0.01,0.44]) y de Vitaniño (RM=0.05 [IC95% 0.005, 0.46]) se asoció con menor momio de diarrea.Es necesario considerar la continuidad del consumo de suplementos nutricionales para mejorar la salud y el estado de micronutrimentos en población infantil mexicana vulnerable.

Hepatic ammonia handling was analyzed in taurine transporter (TauT) KO mice. Surprisingly, hyperammonemia was present at an age of 3 and 12 months despite normal tissue integrity. This was accompanied by cerebral RNA oxidation. As shown in liver perfusion experiments, glutamine production from ammonia was diminished in TauT KO mice, whereas urea production was not affected. In livers from 3-month-old TauT KO mice protein expression and activity of glutamine synthetase (GS) were unaffected, whereas the ammonia-transporting RhBG protein was down-regulated by about 50%. Double reciprocal plot analysis of glutamine synthesis versus perivenous ammonia concentration revealed that TauT KO had no effect on the capacity of glutamine formation in 3-month-old mice, but doubled the ammonia concentration required for half-maximal glutamine synthesis. Since hepatic RhBG expression is restricted to GS-expressing hepatocytes, the findings suggest that an impaired ammonia transport into these cells impairs glutamine synthesis. In livers from 12-, but not 3-month-old TauT KO mice, RhBG expression was not affected, surrogate markers for oxidative stress were strongly up-regulated, and GS activity was decreased by 40% due to an inactivating tyrosine nitration. This was also reflected by kinetic analyses in perfused liver, which showed a decreased glutamine synthesizing capacity by 43% and a largely unaffected ammonia concentration dependence. It is concluded that TauT deficiency triggers hyperammonemia through impaired hepatic glutamine synthesis due to an impaired ammonia transport via RhBG at 3 months and a tyrosine nitration-dependent inactivation of GS in 12-month-old TauT KO mice.

Purpose: Zinc restriction during fetal and postnatal development could program cardiovascular diseases in adulthood. The aim of this study was to determine the effects of zinc restriction during fetal life, lactation, and/or post-weaning growth on cardiac inflammation, apoptosis, oxidative stress, and nitric oxide system of male and female adult rats. Methods: Wistar rats were fed a low- or a control zinc diet during pregnancy and up to weaning. Afterward, offspring were fed either a low- or a control zinc diet until 81 days of life. IL-6 and TNF-α levels, TUNEL assay, TGF-β1 expression, thiobarbituric acid-reactive substances that determine lipoperoxidation damage, NADPH oxidase-dependent superoxide anion production, antioxidant and nitric oxide synthase activity, mRNA and protein expression of endothelial nitric oxide synthase, and serine1177 phosphorylation isoform were determined in left ventricle. Results: Zinc deficiency activated apoptotic and inflammatory processes and decreased TGF-β1 expression and nitric oxide synthase activity in cardiac tissue of both sexes. Male zinc-deficient rats showed no changes in endothelial nitric oxide synthase expression, but a lower serine1177 phosphorylation. Zinc deficiency induced an increase in antioxidant enzymes activity and no differences in lipoperoxidation products levels in males. Females were less sensitive to this deficiency exhibiting lower increase in apoptosis, lower decrease in expression of TGF-β1, and higher antioxidant and nitric oxide enzymes activities. A zinc-adequate diet during postnatal life reversed most of these mechanisms. Conclusion: Prenatal and postnatal zinc deficiency induces alterations in cardiac apoptotic, inflammatory, oxidative, and nitric oxide pathways that could predispose the onset of cardiovascular diseases in adult life. Fil: Juriol, Lorena Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Gobetto, María Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Mendes Garrido Abregú, Facundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Dasso, Marina Ercilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Pineda, Gonzalo Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Güttlein, Leandro. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Carranza, Maria Andrea. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Podhajcer, Osvaldo Luis. Fundación Instituto Leloir; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Toblli, Jorge Eduardo. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Elesgaray, Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Arranz, Cristina Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina Fil: Tomat, Analia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina

This study was carried out to understand the effects of zinc deficiency in rats aged 0∼2 months on learning and memory, and the brain-derived neurotrophic factor (BDNF) gene methylation status in the hippocampus.The lactating mother rats were randomly divided into three groups (n = 12): zinc-adequate group (ZA: zinc 30 mg/kg diet), zinc-deprived group (ZD: zinc 1 mg/kg diet), and a pair-fed group (PF: zinc 30 mg/kg diet), in which the rats were pair-fed to those in the ZD group. After weaning (on day 23), offspring were fed the same diets as their mothers. After 37 days, the zinc concentrations in the plasma and hippocampus were measured, and the behavioral function of the offspring rats was measured using the passive avoidance performance test. We then assessed the DNA methylation patterns of the exon IX of BDNF by methylation-specific quantitative real-time PCR and the mRNA expression of BDNF in the hippocampus by RT-PCR.Compared with the ZA and PF groups, rats in the ZD group had shorter latency period, lower zinc concentrations in the plasma and hippocampus (P 0.05). Interestingly, the DNA methylation of the BDNF exon IX was significantly increased in the ZD group, compared with the ZA and PF groups, whereas the expression of the BDNF mRNA was decreased. In addition, the DNMT1 mRNA expression was significantly upregulated and DNMT3A was downregulated in the ZD group, but not in the ZA and PF groups.The learning and memory damage in offspring may be a result of the epigenetic changes of the BDNF genes in response to the zinc-deficient diet during 0∼2 month period. Furthermore, this work supports the speculative notion that altered DNA methylation of BDNF in the hippocampus is one of the main causes of cognitive impairment by zinc deficiency.

Summary Background Besides being the world's most widely used vaccine, BCG is the most controversial vaccine in current use. Estimates of protection impaired by BCG against pulmonary TB vary from nil to 80%. Dietary zinc deficiency has been confirmed to impair the immune function of animals. However, knowledge about effects of mild dietary zinc deficiency and the time of vaccination on BCG vaccine responsiveness in offspring and adult rats is limited. This work investigated the consequences of feeding zinc deficient and normal zinc diets to rats during gestation, infancy or adulthood on the immune responses to BCG vaccination. Methods On gestation day 0, sixteen maternal rats were divided into two groups and fed with diets bellow: a control diet ad libitum (30 μg zinc/g diet, NC), a zinc deficient diet ad libitum (8 μg zinc/g diet, ZnD). Pup rats were served as experimental subjects. From day 1 of pregnancy upon delivery, maternal rats were given a standard diet (30 mg/kg/day zinc) or zinc deficient diet (8 mg/kg/day zinc) respectively. Adult male 10-week Wistar rats were divided into two dietary groups for 17 weeks of feeding: a control diet ad libitum (30 μg zinc/g diet, NC), a zinc deficient diet ad libitum (8 μg zinc/g diet, ZnD). The birth time of newborn pups was recorded as the zero week. For adult male rats, the time of receiving different assigned diet was recorded as the zeroth week. Newborn pups of these maternal rats were immunized with BCG vaccine or MTB antigen ESAT-6/CFP-10 at postnatal 0 and 2 week. The adult male rats were immunized on the 12th and 14th week. Then, blood samples, thymus and spleen from the rats were harvested for detection of humoral and cell-mediated immune responses using ELISA, MTT and QRT-PCR analysis. Decreased INF-γ and TNF-α production in plasma, changes of expression level of ZIP2, ZIP8, NF-κB and IL-6 mRNA in immune organs, together with reduced T cell proliferation was observed in pups and adult BCG rats suffered from dietary zinc deficiency. Small differences were observed between rats received BCG vaccine and MTB antigen ESAT-6/CFP-10. Results Our data clearly indicate that dietary zinc deficiency can weaken the plasma cytokine levels and cell-mediated responses to BCG and ESAT-6/CFP-10 vaccine via decreasing T cell proliferation, down-regulating INF-γ and TNF-α production and affecting the expression of ZIP2, ZIP8, NF-κB and IL-6 mRNA. In addition, the vaccine immunogenicity of BCG and ESAT-6/CFP-10 was not significantly affected by the time of vaccination.

Systemic and cellular zinc homeostasis is elaborately controlled by ZIP and ZnT zinc transporters. Therefore, detailed characterization of their expression properties is of importance. Of these transporter proteins, Zip4 functions as the primarily important transporter to control systemic zinc homeostasis because of its indispensable function of zinc absorption in the small intestine. In this study, we closely investigated Zip4 protein accumulation in the rat small intestine in response to zinc status using an anti-Zip4 monoclonal antibody that we generated and contrasted this with the zinc-responsive activity of the membrane-bound alkaline phosphatase (ALP). We found that Zip4 accumulation is more rapid in response to zinc deficiency than previously thought. Accumulation increased in the jejunum as early as 1 day following a zinc-deficient diet. In the small intestine, Zip4 protein expression was higher in the jejunum than in the duodenum and was accompanied by reduction of ALP activity, suggesting that the jejunum can become zinc deficient more easily. Furthermore, by monitoring Zip4 accumulation levels and ALP activity in the duodenum and jejunum, we reasserted that zinc deficiency during lactation may transiently alter plasma glucose levels in the offspring in a sex-specific manner, without affecting homeostatic control of zinc metabolism. This confirms that zinc nutrition during lactation is extremely important for the health of the offspring. These results reveal that rapid Zip4 accumulation provides a significant conceptual advance in understanding the molecular basis of systemic zinc homeostatic control, and that properties of Zip4 protein accumulation are useful to evaluate zinc status closely.

The aim of this study was to investigate the effect of either sheep or cow milk supplementation to a low calcium and phosphorus diet on growth and organ mineral distribution in weanling rats. Rats were fed diets consisting of either a control chow, a 50% reduced calcium and phosphorous chow (low Ca/P), low Ca/P and sheep milk, or low Ca/P and cow milk diet for 28 days. Food intake of the rats, the growth rate of the rats, and the concentrations of minerals in the soft organs and serum were determined. Rats fed the low Ca/P diet alone had lower weight gain than rats consuming either of the milk-supplemented diets (p &lt, 0.05). Both sheep milk and cow milk supplementation overcame the effects of consuming a diet restricted in calcium and phosphorus but the sheep milk was effective at a significantly lower level of milk intake (p &lt, 0.05). Significant differences (p &lt, 0.05) in essential and trace mineral concentrations due to milk type were observed in the kidney, spleen, and liver. For non-essential minerals, significant differences (p &lt, 0.05), related to diet, were observed in all organs for arsenic, cesium, rubidium, and strontium concentrations.

Iron is the most common micronutrient deficiency in the world and it is most prevalent in young children, exposing their developing brain to inadequate iron levels. The damage related to neuroanatomical parameters is not reversed after iron treatment. However, evidence suggest that tactile stimulation (TS) may offer great therapeutic efficacy in cases of nutritional disorders postnatally, since the brain is remarkably responsive to its interaction with the environment. Recently, we shown that neonatal iron deficient rats achieved some remedial effect by exposing them to TS treatment early in life, reinforcing the fact that the TS approach is a positive enriching experience, therefore, here we ask whether exposure to TS treatment, could also be employed to prevent fine structural changes in the fibers from optic nerve of rats maintained on an iron-deficient diet during brain development. To elucidate the protective effect of tactile stimulation, our methods resulted in 10,859 analyzed fibers, divided into small and large fibers. We found that iron deficiency led to a decreased axon, fiber and myelin size of small fibers, however, TS completely reversed the iron-decifiency-induced alteration on those fiber measurements. Large fibers were disproportionately affected by iron deficiency and there was no remediating effect due to tactile stimulation treatment. The present study adds new information regarding different alterations between small and large fibers due to diet and TS, which suggest a size-based selectivity. These results emphasize the concept that compromised brain development can be mitigated at an early age by environmental factors, such as tactile stimulation.