Verification of Nuclear Magnetic Resonance Characterization of Traditional Homeopathically Manufactured Metal (Cuprum metallicum) and Plant (Gelsemium sempervirens) Medicines and Controls.

BACKGROUND: Nuclear magnetic resonance (NMR) proton relaxation is sensitive to the dynamics of the water molecule, H2O, through the interaction of the spin of the proton (1H) with external magnetic and electromagnetic fields. NMR relaxation times describe how quickly the spin of 1H, forced in a direction by an external electromagnetic field, returns to a normal resting position. As a result, such measurements allow us potentially to describe higher structuring of water in homeopathic medicines. OBJECTIVE: The purpose of the present study was to verify whether specific NMR relaxation times could be measured in full lines of cH dynamizations of a metal (copper) and of a plant substance (Gelsemium sempervirens), compared with a solvent control, a potentized lactose control and a control prepared by simple dilution, in three production lines. It is aimed at verification of a previous publication (2017) on two new manufacturing lines of the same starting material and controls. MATERIALS AND METHODS: To monitor dilution and potentization processes, measurements of 1H spin-lattice T1 and spin-spin T2 relaxation times were used. T1 and T2 relaxation times were measured at 25°C with a spin analyser working at a frequency of 20 MHz. To account for its possible role as a confounding factor, free oxygen was also measured in all samples, using a MicroOptode meter. RESULTS: When the values of the three production lines were pooled, a statistically significant discrimination of NMR relaxation times between the medicines and their controls was confirmed. We found for copper cH and Gelsemium sempervirens cH a highly significant influence of the starting material (p = 0.008), a highly significant influence of level of dilution (p < 0.001), and a significant influence of the O2 concentration (p = 0.04). CONCLUSIONS: We have evidence of an obvious retention of a specific magnetic resonance signal when a substance (lactose, copper, Gelsemium) is diluted/potentized in pure water. This means that homeopathic solutions cannot be considered to be pure water. O2 is a covariant and not an explanatory variable: this factor itself is too weak to explain the NMR signal specificities in potentized samples. Homeopathic dilutions may thus have a specific material configuration governed not only by the potentized substance but also by the chemical nature of the containers, the chemical nature of dissolved gases and even by the electromagnetic environment. This sensitivity of homeopathically prepared medicines to electromagnetic fields may be amplified by the processes routinely applied during their preparation; because it occurs only when a dynamization has been performed, we may call this phenomenon "dynamic pharmacy".

A pilot study into a possible relationship between diet and stuttering.

PURPOSE: There are theoretical and empirical reasons to consider a potential role for copper metabolism in the brain in how it could influence stuttering. However, a link between stuttering and dietary intake has never been researched in a systematic way. This pilot study therefore aimed to explore a possible association between ingested amounts of copper and thiamine (vitamin B1) with stuttering frequency using a double blind cross-over longitudinal paradigm. METHODS: 19 adults who stutter between 20 and 51 years old filled out an online survey for 9 consecutive weeks. The survey consisted of self-assessed fluency and mood state scales, as well as food journals. After 4 weeks, the participants consumed either copper or thiamine supplements for 2 weeks, followed by a 1-week washout period, and another period of two weeks taking the other supplement. Formal speech assessments were done pre/post baseline and at the end of each supplement intake. Participants were not informed about the nature of the supplements during the experiment and the investigators were blinded to the order of the supplements. RESULTS: The results demonstrated that copper and thiamine had no measurable effect on the amount of stuttering (self and formal assessments) but there was a moderate, significant correlation between mood state and fluency. CONCLUSION: The findings do not support notions of dietary influences of ingested copper or thiamine on stuttering but do provide modest support for a relationship between variations in stuttering and self-perceived anxiety.

Perspectives on the Role and Relevance of Copper in Cardiac Disease.

Cardiac hypertrophy as a result of dietary copper deficiency has been studied for 40 plus years and is the subject of this review. While connective tissue anomalies occur, a hallmark pathology is cardiac hypertrophy, increased mitochondrial biogenesis, with disruptive cristae, vacuolization of mitochondria, and deposition of lipid droplets. Electrocardiogram abnormalities have been demonstrated along with biochemical changes especially as it relates to the copper-containing enzyme cytochrome c oxidase. The master controller of mitochondrial biogenesis, PGC1-α expression and protein, along with other proteins and transcriptional factors that play a role are upregulated. Nitric oxide, vascular endothelial growth factor, and cytochrome c oxidase all may enhance the upregulation of mitochondrial biogenesis. Marginal copper intakes reveal similar pathologies in the absence of cardiac hypertrophy. Reversibility of the copper-deficient rat heart with a copper-replete diet has resulted in mixed results, depending on both the animal model used and temporal relationships. New information has revealed that copper supplementation may rescue cardiac hypertrophy induced by pressure overload.

What has fluorescent sensing told us about copper and brain malfunction?

There is growing evidence that copper and copper-binding proteins are common denominators in the mechanisms of neurodegenerative diseases such as Alzheimer's and Parkinson's. These pathologies have been linked to changes in copper homeostasis, but the question of whether this is a causal or effective relationship remains unanswered. A clearer understanding will require a way to visualise copper at a molecular level in vivo. Fluorescent metal sensing is one such tool, and a number of Cu(i) probes have been reported with excellent sensing properties and complementary studies that validate their biological application. This review critically evaluates the recent progress in fluorescent copper sensing and suggests some new directions for future study of copper neurochemistry.

Dietary copper supplementation improves pelt characteristics of female silver fox (Vulpes fulva) during the winter fur-growing season.

Copper has an essential role in normal fur pigmentation and fur quality. This study evaluated the effects of cupric citrate (CuCit) supplementation on growth, nutrients metabolism and pelt characteristics of the female silver fox (Vulpes fulva). Fifty age-matched female silver foxes with similar body weights were randomly divided into five dietary groups for 58 days during the winter fur-growing season. The basal diet contained 4.92 mg/kg copper. Groups I-V were supplemented with 6, 30, 60, 90 or 150 mg Cu from CuCit per 1 kg dry matter basal diet. Serum alkaline phosphatase activity was significantly higher (P<0.05) in those fed 90 mg/kg Cu than those fed 150 mg/kg Cu. Pelt total thickness was significantly higher (P<0.05) in those fed 30 mg/kg Cu than foxes fed 6 mg/kg Cu supplemented diet, but were similar to the other groups. Length of guard hair was significantly lower (P<0.05) in those fed 90 mg/kg Cu than fed 6 mg/kg Cu and 30 mg/kg Cu, but were similar to the other groups. Length of underhair was significantly higher (P<0.05) in those fed 6 mg/kg Cu than those fed 90 mg/kg Cu, but was similar to the other groups. Considering decreasing environmental contamination and improving pelt performance, supplementing 30 mg/kg Cu from CuCit (actual copper 35 mg/kg dry matter) is appropriate for female silver fox.

Metal ions in macrophage antimicrobial pathways: emerging roles for zinc and copper.

The immunomodulatory and antimicrobial properties of zinc and copper have long been appreciated. In addition, these metal ions are also essential for microbial growth and survival. This presents opportunities for the host to either harness their antimicrobial properties or limit their availability as defence strategies. Recent studies have shed some light on mechanisms by which copper and zinc regulation contribute to host defence, but there remain many unanswered questions at the cellular and molecular levels. Here we review the roles of these two metal ions in providing protection against infectious diseases in vivo, and in regulating innate immune responses. In particular, we focus on studies implicating zinc and copper in macrophage antimicrobial pathways, as well as the specific host genes encoding zinc transporters (SLC30A, SLC39A family members) and CTRs (copper transporters, ATP7 family members) that may contribute to pathogen control by these cells.

Selected macro/micronutrient needs of the routine preterm infant.

Requirements for optimal nutrition, especially for micronutrients, are not well defined for premature infants. The "reference fetus," developed by Ziegler et al,(1) has served as a model to define nutritional needs and studies designed to determine nutrient requirements. Revision of nutrient requirements and provision of optimal nutrition may lead to improved outcomes in preterm infants. Appropriate provision of nutrients also may help prevent nutritional disorders, such as metabolic bone disease and anemia. In this review, we discuss calcium, phosphorus, magnesium, vitamin D, iron, and copper, and define optimal intakes based on the available published data.

Limbic system pathologies associated with deficiencies and excesses of the trace elements iron, zinc, copper, and selenium.

Deficiencies of nutrients such as amino acids, vitamins, lipids, and trace elements during gestation and early infanthood have strong deleterious effects on the development of the limbic system; these effects may be irreversible, even when adequate supplementation is provided at later developmental stages. Recent advances in the neurochemistry of biometals are increasingly establishing the roles of the trace elements iron, copper, zinc, and selenium in a variety of cell functions and are providing insight into the repercussions of deficiencies and excesses of these elements on the development of the central nervous system, especially the limbic system. The limbic system comprises diverse areas with high metabolic demands and differential storage of iron, copper, zinc, and selenium. This review summarizes available evidence suggesting the involvement of these trace elements in pathological disorders of the limbic system.

Earthing the human body influences physiologic processes.

OBJECTIVES: This study was designed to answer the question: Does the contact of the human organism with the Earth via a copper conductor affect physiologic processes? Subjects and experiments: Five (5) experiments are presented: experiment 1-effect of earthing on calcium-phosphate homeostasis and serum concentrations of iron (N = 84 participants); experiment 2-effect of earthing on serum concentrations of electrolytes (N = 28); experiment 3-effect of earthing on thyroid function (N = 12); experiment 4-effect of earthing on glucose concentration (N = 12); experiment 5-effect of earthing on immune response to vaccine (N = 32). Subjects were divided into two groups. One (1) group of people was earthed, while the second group remained without contact with the Earth. Blood and urine samples were examined. RESULTS: Earthing of an electrically insulated human organism during night rest causes lowering of serum concentrations of iron, ionized calcium, inorganic phosphorus, and reduction of renal excretion of calcium and phosphorus. Earthing during night rest decreases free tri-iodothyronine and increases free thyroxine and thyroid-stimulating hormone. The continuous earthing of the human body decreases blood glucose in patients with diabetes. Earthing decreases sodium, potassium, magnesium, iron, total protein, and albumin concentrations while the levels of transferrin, ferritin, and globulins α1, α2, ß, and γ increase. These results are statistically significant. CONCLUSIONS: Earthing the human body influences human physiologic processes. This influence is observed during night relaxation and during physical activity. Effect of the earthing on calcium-phosphate homeostasis is the opposite of that which occurs in states of weightlessness. It also increases the activity of catabolic processes. It may be the primary factor regulating endocrine and nervous systems.

Influence of copper on early development: prenatal and postnatal considerations.

Copper (Cu) is an essential nutrient whose requirement is increased during pregnancy and lactation. These represent times of critical growth and development, and the fetus and neonate are particularly vulnerable to deficiencies of this nutrient. Genetic mutations that predispose the offspring to inadequate stores of Cu can be life threatening as is observed in children with Menkes disease. During the last decade, severe Cu deficiency, once thought to be a rare condition, has been reported in the literature at an increasing frequency. Secondary Cu deficiencies can be induced by a variety of ways such as excessive zinc or iron intake, certain drugs, and bariatric surgery. Premature and low birth weight infants can be born with low Cu stores. A number of mechanisms can contribute to the teratogenicity of Cu including decreased activity of select cuproenzymes, increased oxidative stress, decreased nitric oxide availability, altered iron metabolism, abnormal extracellular matrix protein crosslinking, decreased angiogenesis and altered cell signaling among others. The brain, heart, and vessels as well as tissues such as lung, skin and hair, and systems including the skeletal, immune, and blood systems, are negatively affected by suboptimal Cu during development. Additionally, persistent structural, biochemical, and functional adverse effects in the offspring are noted even when Cu supplementation is initiated after birth, supporting the concept that adequate Cu nutriture during pregnancy and lactation is critical for normal development. Although Cu-containing IUDs are an effective method for increasing intrauterine Cu concentrations and for reducing the risk of pregnancy, high amounts of dietary Cu are not thought to represent a direct developmental risk.

The metal chelating and chaperoning effects of clioquinol: insights from yeast studies.

Clioquinol (CQ), a once popular antibiotic, was used to inhibit the growth of microorganisms. Recently, CQ and its analog PBT2 have shown encouraging effects in the animal and clinical trials for Alzheimer's disease (AD). However, the mechanism by which this class of molecules works remains controversial. In this work, we used the yeast Saccharomyces cerevisiae as a model to study how CQ affects molecular and cellular functions and particularly, copper, iron, and zinc homeostasis. We observed a CQ-induced inhibition of yeast growth, which could be slightly relieved by supplementation of copper or iron. Microarray results indicated that yeast cells treated with CQ sense a general deficiency in metals, despite elevated total cellular contents of copper and iron. Consistent with this, reduced activities of some metal-sensitive enzymes were observed. Intriguingly, CQ can increase the SOD1 activity, likely through Ccs1's accessibility to CQ-bound copper ions. Further studies revealed that CQ sequestrates copper and iron at the cellular membrane, likely the plasma membrane, resulting overall metal accumulation but cytosolic metal depletion. CQ's effects on metal-sensitive metalloenzymes were also verified in mammalian cell line SH-SY5Y. Together, our results revealed that CQ can regulate metal homeostasis by binding metal ions, resulting the cell sensing a state of deficiency of bioavailable metal ions while simultaneously increasing available metals to SOD1 (via Ccs1) and possibly some other metalloproteins that can access CQ-bound metals. We hope this regulation of metal homeostasis may be helpful in explaining the therapeutic effects of CQ used in disease treatment.

Inactivation of cytochrome c oxidase by mutant SOD1s in mouse motoneuronal NSC-34 cells is independent from copper availability but is because of nitric oxide.

The copper-enzyme cytochrome c oxidase (Cytox) has been indicated as a primary molecular target of mutant copper, zinc superoxide dismutase (SOD1) in familial amyotrophic lateral sclerosis (fALS); however, the mechanism underlying its inactivation is still unclear. As the toxicity of mutant SOD1s could arise from their selective recruitment to mitochondria, it is conceivable that they might compete with Cytox for the mitochondrial copper pool causing Cytox inactivation. To investigate this issue, we used mouse motoneuronal neuroblastoma x spinal cord cell line-34, stably transfected for the inducible expression of low amounts of wild-type or mutant (G93A, H46R, and H80R) human SOD1s and compared the effects observed on Cytox with those obtained by copper depletion. We demonstrated that all mutants analyzed induced cell death and decreased the Cytox activity, but not the protein content of the Cytox subunit II, at difference with copper depletion that also affected subunit II protein. Copper supplementation did not counteract mutant hSOD1s toxicity. Otherwise, the treatment of neuroblastoma x spinal cord cell line-34 expressing G93A, H46R, or H80R hSOD1 mutants, and showing constitutive expression of iNOS and nNOS, with either a NO scavenger, or NOS inhibitors prevented the inhibition of Cytox activity and rescued cell viability. These results support the involvement of NO in mutant SOD1s-induced Cytox damage, and mitochondrial toxicity.

Suplementación con cobre entre comidas no tiene efecto sobre la nutrición de hierro en hombres / Copper supplementation between meals has no effect on iron status of men

Iron deficiency is prevalent in most of the developing world where it coexists with other micronutrient deficiencies such as copper. Combined supplementation with iron and copper is one of the strategies that can be used to improve the iron and copper status of a population. However, there is concern about potential negative interactions between these two micronutrients due to a competitive binding to the divalent metal transporter 1 (DMTl), a proton-coupled transporter of a variety of divalent metals including copper. The aim of this study was to measure the effect of daily supplementation with 8 mg of copper, as copper sulfate during 6 months on the iron status. Sixty healthy male adults were randomized to receive a copper supplement or a placebo. Fasting blood samples were obtained before and after copper supplementation to evaluate the iron and copper nutritional status. Copper supplementation did not change significantly iron and copper status parameters. In conclusion, daily supplementation with 8 mg of copper during 6 months does not deteriorate iron nutrition in adult men.

La deficiencia de hierro coexiste con otras carencias, entre ellas de cobre. La suplementación combinada con estos nutrientes es una de las estrategias utilizadas en su prevención. Sin embargo, existe la posibilidad de interacciones negativas, ya que el DMT1, principal transportador de hierro no hem a nivel intestinal, también transporta cobre. El propósito del estudio fue medir el efecto de la suplementación con 8 mg diarios de cobre, como sulfato de cobre, durante 6 meses, sobre la nutrición de hierro. Sesenta hombres adultos, aparentemente sanos, fueron seleccionados al azar para recibir el suplemento de cobre o un placebo. Se tomaron muestras de sangre en ayunas antes y después de finalizada la suplementacion para evaluar la nutrición de hierro y de cobre. La suplementacion con cobre no determinó cambios significativos en los indicadores de nutrición de cobre y de hierro. En conclusión, la suplementacion con 8 mg diarios de Cu administrado entre comidas durante 6 meses no deterioró la nutrición de hierro en hombres adultos.

The alkyl chain length of 3-alkyl-3',4',5,7-tetrahydroxyflavones modulates effective inhibition of oxidative damage in biological systems: illustration with LDL, red blood cells and human skin keratinocytes.

It is shown that the relationship between the alkyl chain length of 3-alkyl-3',4',5,7 tetrahydroxyflavones (FnH) bearing alkyl chains of n=1, 4, 6, 10 carbons and their capacity to counter oxidative damage varies markedly with the nature of the biological system. In Cu(2+)-induced lipid peroxidation of low-density lipoprotein (LDL), the less hydrophobic short-chain F1H and F4H are probably located in the outer layer of LDL and parallel the reference flavonoid antioxidant, quercetin (Q) as effective inhibitors of lipid peroxidation. A marked inhibition of haemolysis induced in red blood cells (RBC) suspensions by the membrane-permeant oxidant, tert-butylhydroperoxide (t-BuOOH), is observed with F4H and F6H present at concentration in the micromolar range. However, F10H the most hydrophobic FnH is even more effective than Q against both haemolysis and lipid peroxidation as measured by malondialdehyde (MDA) equivalents. In oxidation of RBC by H(2)O(2,) at least 50 times more F6H and F10H than by t-BuOOH are required to only partly inhibit haemolysis and MDA production. The F1H, F4H and Q are found rather inactive under these conditions. At concentrations in the micromolar range, a marked protection against the cytotoxic effects of the t-BuOOH-induced oxidative stress in human skin NCTC 2544 keratinocytes is also exhibited by the four FnH antioxidants and is comparable to that of Q. Thus, the four FnH species under study may be considered as potent antioxidants which manifest complementary anti-oxidative actions in biological systems of markedly different complexity.

Iron, copper and immunocompetence.

Microminerals including copper and iron are essential to immunity and health in human beings. The development of powerful tools in analytical cell biology and molecular genetics has facilitated efforts to identify specific cellular and molecular functions of trace elements in the maturation, activation and functions of host defence mechanisms. Selected recent reports about the role of copper and iron nutrition on immune functions are critically analysed here. Effects of trace element supplementation on infectious morbidity are also reviewed. While micromineral deficiencies, in general, may have widespread effects on nearly all components of immune response, these effects can be reversed by supplementation. However, the conflicting effects of iron deficiency and iron supplementation in vitro on the defensive systems reveals the urgent need for further additional information on the in vivo situation. In the elderly, vaccination against respiratory infections is likely to protect only 30-70% of the population. However, it may be possible to modulate immune function and ultimately reduce the severity of infections through micronutrient supplementation. Thus, microminerals contribute to the maintenance of the balance between immunity and health in humans.

Identification and functional characterisation of ctr1, a Pleurotus ostreatus gene coding for a copper transporter.

Copper homeostasis is crucial for the maintenance of life. In lignin-degrading fungi, copper is essential for the phenol oxidase enzymes that provide this activity. In this paper we report the characterization of a gene (ctr1) coding for a copper transporter in the white rot fungus Pleurotus ostreatus. The gene was identified in a cDNA library constructed from 4-day-old vegetative mycelium grown in liquid culture. The results presented here demonstrate that: (1) ctr1 functionally complements the respiratory deficiency of a yeast mutant defective in copper transport, supporting the idea that the Ctr1 protein is itself a copper transporter; (2) transcription of ctr1 is detectable in P. ostreatus at all developmental stages and in all tissues (with the exception of lamellae), and is negatively regulated by the presence of copper in the culture medium; (3) ctr1 is a single-copy gene that maps to P. ostreatus linkage group III; and (4) the regulatory sequence elements found in the promoter of ctr1 are similar to those found in other copper-related genes described in other systems. These results provide the first description of a copper transporter in this white rot fungus and should be useful for further studies on copper metabolism in higher basidiomycetes.

Copper modifies the activity of sodium-transporting systems in erythrocyte membrane in patients with essential hypertension.

The aim of the study was to verify the hypothesis if copper could influence the activity of sodium-transporting systems in erythrocyte membrane that could be related to essential hypertension. The examined group of patients consisted of 15 men with hypertension. The control group was 11 healthy male volunteers. The Na+/H+ exchanger (NHE) activity in erythrocytes was determined according to Orlov et al. The activity of transporting systems (ATP-Na+/K+; co-Na+/K+/Cl-; ex-Na+/Li+; free Na+ and K+ outflow [Na+, K+-outflow]) was determined according to Garay's method. The concentration of copper in plasma was assessed using atomic absorption spectrometry. The activity of ATP-Na+/K+ (micromol/L red blood cells [RBCs]/h) in hypertensive patients was 2231.5 +/- 657.6 vs 1750.5 +/- 291 in the control (p < 0.05), the activity of co-Na+/K+/Cl- (micromol/L RBCs/h) in hypertensives was 171.3 +/- 77.9 vs 150.7 +/- 53.9 in the control (NS). Na+-outflow (micromol/L RBCs/h) in hypertensives was 118.3 +/- 51.6 vs 113.3 +/- 24.4 in the control (NS). The K+-outflow (micromol/L RBCs/h) in hypertensives was 1361.7 +/- 545.4 vs 1035.6 +/- 188.3 in the control (NS). The activity of ex-Na+/Li+ (micromol/L RBCs/h) in hypertensive patients was 266.1 +/- 76.1 vs 204.1 +/- 71.6 in the control (p < 0.05). NHE activity (mmol/L RBCs/h) in hypertensives was 9.7 +/- 2.96 vs 7.7 +/- 1.33 in the control (p < 0.05). In hypertensive patients, negative correlation was found between the activity of Na+/K+/Cl- co-transport and plasma copper concentration (Rs = -0.579, p < 0.05) and between the activity of ex-Na+/Li+ and plasma copper concentration (Rs = -0.508, p < 0.05). Plasma copper concentration significantly influences the activity of sodium transporting systems in erythrocyte membrane. Copper supplementation could be expected to provide therapeutic benefits for hypertensive patients.

Effect of copper status, supplementation, and source on pituitary responsiveness to exogenous gonadotropin-releasing hormone in ovariectomized beef cows.

The effect of Cu status, supplementation, and source on pituitary responsiveness to exogenous GnRH was evaluated using nine multiparous, nonpregnant, nonsuckling, ovariectomized Angus cows (7.1 +/- 3.3 yr; 622.9 +/- 49.8 kg; BCS = 6.0 +/- 0.5). Cows were considered Cu-deficient based on liver Cu concentrations (< 30 mg of Cu/kg of DM) after receiving a low-Cu, forage-based diet supplemented (DM basis) with 5 mg of Mo/kg and 0.3% S for 216 d. Copper-deficient cows were stratified based on age, BW, BCS, and liver Cu concentration and assigned randomly to repletion-phase treatments. Treatments included 1) control (no supplemental Cu); 2) organic (ORG; 100% organic Cu); and 3) inorganic (ING; 100% inorganic CuSO4). Treatments were formulated to meet all NRC recommendations, except for Cu, which was supplemented to ORG and ING cows at 10 mg of Cu/kg of dietary DM. During the 159-d repletion phase, Cu status was monitored via liver biopsy samples, and all cows received exogenous progesterone. A controlled intravaginal drug-release device (replaced every 14 d) was used to maintain luteal phase progesterone as a means to provide negative feedback on the hypothalamic-pituitary axis. During the repletion phase, liver Cu concentrations did not differ between ORG and ING cows at any time. By d 77 of the repletion phase, all supplemented cows were considered adequate in Cu, and liver Cu concentrations were greater in supplemented than in nonsupplemented control cows on d 77 (P < 0.05) and throughout (P < 0.01) the repletion phase. Beginning on d 99, exogenous GnRH was administered to all cows at low (0, 3, and 9 microg; Exp. 1) and high doses (0, 27, and 81 microg; Exp. 2) at six different times. Cows were catheterized every fifth day, and blood samples were collected every 15 min for 1 h before and 4 h after GnRH administration and analyzed for LH concentration. In Exp. 1, Cu status and supplementation did not affect basal or peak LH concentrations, but total LH released tended (P < 0.07) to be greater in Cu-supplemented vs. control cows when 3 microg of GnRH was administered. In Exp. 2, there was no effect of Cu supplementation or source on basal, peak, or total LH released, regardless of GnRH dose. Pituitary LH concentrations did not differ across treatments. In conclusion, Cu status, supplementation, and source did not affect GnRH-induced LH secretion or pituitary LH stores in ovariectomized, progesterone-supplemented cows in this experiment.

Differential response of interleukin-2 production to chronic copper supplementation in healthy humans.

BACKGROUND: Copper (Cu) is an essential trace element for many biological processes including maintenance of both innate and acquired branches of immunity. OBJECTIVE: To measure the effect of copper supplementation on IL-2 and TNF-alpha production in subjects with lower and higher ceuloplasmin (Cp) values within normal range. DESIGN: Healthy adults (17 men and 16 women) with normal-low (low Cp) and normal-high Cp (high Cp) values were supplemented with 10 mg Cu/day (as CuSO(4)) during 2 months. METHOD: Before and after supplementation blood mononuclear cells were incubated in the absence or presence of phytohaemagglutinin or lipopolysaccharide for induction of IL-2 and TNF-alpha, respectively. The secretion of cytokines was measured by ELISA. Cu supplementation did not modify classical biochemical markers of Cu status. RESULTS: After supplementation, a significant increase in IL-2 production was found only in subjects with normal-low plasma Cp. Before and after Cu supplementation geometric mean and range +/- 1 SEM values were 1,566 (1,287-1,905) and 2,514 (2,159-2,927) pg/mL, respectively (two-way ANOVA for repeated measures: Cp level p < 0.001; time = NS; interaction Cp level and time p < 0.05). We did not observe changes in TNF-alpha production after Cu supplementation. CONCLUSIONS: Cu supplementation increased secretion of IL-2 and not TNF-alpha, which suggests an activation of proliferative but not inflammatory cytokines. These results support hypothesis that IL-2 may be a good indicator to identify a subgroup of individuals (polymorphism) who differs in Cu metabolism.