Comparison of zinc acetate hydrate and polaprezinc for zinc deficiency in patients on maintenance hemodialysis: A single-center, open-label, prospective randomized study.

The efficacy and safety of zinc acetate hydrate (ZAH) for zinc supplementation in patients on maintenance hemodialysis (MHD) remains unknown. In this prospective, single-center, open-label, parallel-group trial for MHD patients with serum zinc level <70 µg/dL, we compared ZAH (zinc; 50 mg/day) and polaprezinc (PPZ; zinc; 34 mg/day) beyond 6-month administration in a 1:1 randomization manner. The ZAH and PPZ groups had 44 and 47 patients, respectively. At 3 months, the change rate of serum zinc levels in the ZAH group was significantly higher than that in the PPZ group. Three months after the study, serum copper levels significantly decreased in the ZAH group, but not in the PPZ group. No significant differences were noted in anemia management in either group. ZAH was superior to PPZ in increasing serum zinc levels. Clinicians should note the stronger decline in serum copper levels when using ZAH for MHD patients.

Toxicity and serum metabolomics investigation of Mn-doped ZnS quantum dots in mice.

PURPOSE: Mn-doped ZnS quantum dots (QDs) with special luminescent properties have been widely researched and applied in various fields. Thus, their release toxicity and security cannot be ignored. METHODS: In the present study, the toxicity and non-targeted metabolomics of Mn-doped ZnS QDs were investigated after single intravenous injection. Serum metabolites were evaluated based on gas chromatography-mass spectrometry together with multivariate statistical analyses [principal component analysis, partial least squares discriminant analysis, and orthogonal PLS-DA]. RESULTS: The modified metabolites (variable importance in the projection (VIP) >1 and p<0.05) revealed that Mn-doped ZnS QDs exposure disturbed glycolysis, tricarboxylic acid cycle, ketoplasia, glutaminolysis, and amino acid and lipid metabolism. The behavior, coefficients of organs, and histological changes were the same as in the control group, and the disturbance of hematology and serum biochemistry was not dose- or time-dependent. CONCLUSION: Our study provides a general observation regarding the toxicity and potential metabolic responses of mice exposed to Mn-doped ZnS QDs.

Comparison of the Biological Impacts of the Fluoride Compounds by Graphical Risk Visualization Map Technique.

Various fluoride compounds are widely used in industry. The present risk assessment study was conducted using a series of inorganic binary fluorides of the type XFn, where X(n) = Na(+), K(+), Li(+), Mg(2+), Ca(2+), Sr(2+), Ba(2+), Al(3+), Nd(3+), La(3+), Ce(3+), Sm(3+), Gd(3+), Y(3+), Yb(2+), and Zn(2+). The aqueous solutions of these salts were orally administrated to 16 experimental groups (one for each of the salts tested). The levels of fluoride, N-acetyl-ß-D-glucosaminidase in cumulative 24-h urine samples and creatinine clearance were measured to assess possible acute renal damages. The levels of fluoride, alanine aminotransferase, and aspartate aminotransferase were also determined in serum samples to assess possible acute hepatic damages. The results reveal that sodium fluoride (NaF), potassium fluoride (KF), and zinc fluoride tetrahydrate (ZnF2 (.)4H2O) can carry the fluoride ion into the bloodstream and that it is excreted via urine more readily than the other compounds tested. These fluorides were assigned the highest risk impact factor. Most of the rare earth fluorides are insoluble in water while those groups 2 and 13 of the periodic table are slightly soluble, so that they do not have a significant negative risk. These findings suggest that the biological impact of fluoride depends on the accompanying counter ion and its solubility. The risk map obtained in the present study shows that the graphical visualization map technique employed is a valuable new tool to assess the toxicological risk of chemical compounds.

Degradation of aqueous synthesized CdTe/ZnS quantum dots in mice: differential blood kinetics and biodistribution of cadmium and tellurium.

BACKGROUND: Quantum dots (QDs) have been used as novel fluorescent nanoprobes for various bioapplications. The degradation of QDs, and consequent release of free cadmium ions, have been suggested to be the causes of their overall toxicity. However, in contrast to sufficient investigations regarding the biological fate of QDs, a paucity of studies have reported their chemical fate in vivo. Therefore, the overall aim of our study was to understand the chemical fate of QDs in vivo and explore analytical techniques or methods that could be used to define the chemical fate of QDs in vivo. METHODS: Male ICR mice were administered a single intravenous dose (0.2 µmol/kg) of aqueous synthesized CdTe/ZnS aqQDs. Inductively coupled plasma-mass spectrometry (ICP-MS) was used to simultaneously measure the concentrations of cadmium (Cd) and tellurium (Te) in the blood and tissues over the course of a 28 day period. We compared the blood kinetic parameters and biodistributions of Cd and Te, and used the molar ratio of Cd:Te as a marker for QDs degradation. RESULTS: Cd and Te display different blood kinetics and biodistribution profiles. The Cd:Te ratio in the blood did not vary significantly within the first hour compared with intact CdTe/ZnS aqQDs. The Cd:Te ratio decreased gradually over time from the 6 h time point on. Cd accumulated in the liver, kidneys, and spleen. Te was distributed primarily to the kidneys. Sharp time-dependent increases in the Cd:Te ratio were found in liver tissues. CONCLUSIONS: QDs can undergo degradation in vivo. In vitro, QDs are chemically stable and do not elicit the same biological responses or consequences as they do in vivo. Our methods might provide valuable information regarding the degradation of QDs in vivo and may enable the design and development of QDs for biological and biomedical applications.

The role of zinc in the treatment of taste disorders.

In the 1990s the number of patients diagnosed with taste disorders in the USA and Japan was over one million people each year, and the number is increasing annually. Taste disorders are caused by several factors such as genetic disease, head trauma, structural changes, glossodynia, cancer, change of lifestyle, and more. The role of zinc in the treatment of taste disorders has been studied since the oral administration of zinc by patients was reported to improve their taste disorders. Carbonic anhydrase (CA), a zinc metalloenzyme, has also been studied in association with taste disorders, since the regulation of serum CA levels was shown to influence the effect of orally administrated zinc in the treatment of taste disorders. Zinc is an essential trace element that contributes to the active center of approximately 300 enzymes. Studies have revealed that zinc is involved in various physiological functions. Moreover, some medications have been shown to induce a zinc deficiency, which has been associated with a variety of clinical conditions. Hence, since the relationship between taste disorder and serum zinc concentration has been discussed for long time, taste disorder may be useful in diagnosing zinc deficiency. Moreover, it appears that medicines of the zinc-containing supplement type contribute to the treatment of taste disorders caused by zinc deficiency. Orally administered zinc has been shown to directly stimulate food intake via neuropeptide in the hypothalamus. Therefore, zinc administration may potentially be used to treat taste disorders, as well as several other diseases by stimulating feeding. The article presents some promising patents on the role of zinc in the treatment of taste disorders.

Bioavailability of zinc sources and their interaction with phytates in broilers and piglets.

Zinc (Zn) is essential for swine and poultry and native Zn concentrations in feedstuffs are too low to meet their Zn requirement. Dietary Zn bioavailability is affected by phytate, phytase and Zn supplemented in organic form is considered as more bioavailable than inorganic sources. A meta-analysis using GLM procedures was processed using broiler and piglet databases to investigate, within the physiological response of Zn, (1) the bioavailability of inorganic and organic Zn sources (Analysis I); (2) the bioavailability of native and inorganic Zn dependent from dietary phytates, vegetal and supplemental phytase activity (Analysis II). Analysis I: the bioavailability of organic Zn relative to inorganic Zn sources ranged, depending on the variable, from 85 to 117 never different from 100 (P > 0.05). The coefficients of determination of the regressions were 0.91 in broilers and above 0.89 in piglets. Analysis II: in broilers, bone Zn was explained by supplemental Zn (linear and quadratic, P < 0.001) and by supplemental phytase (linear, P < 0.001). In piglets, the interaction between dietary Zn and phytates/phytases was investigated by means of a new variable combining dietary phytic phosphorus (PP) and phytase activity. This new variable represents the remaining dietary PP after its hydrolysis in the digestive tract, mainly due to phytase and is called non-hydrolyzed phytic phosphorus (PP(NH)). Bone Zn was increased with native Zn (P < 0.001), but to a lower extent in high PP or low phytase diets (ZN(N) × PP(NH), P < 0.001). In contrast, the increase in bone zinc in response to supplemental Zn (P < 0.001) was not modulated by PP(NH) (P > 0.05). The coefficients of determination of the regressions were 0.92 in broilers and above 0.92 in piglets. The results from the two meta-analyses suggest that (1) broilers and piglets use supplemented Zn, independent from Zn source; (2) broiler use native Zn and the use is slightly enhanced with supplemental phytase; (3) however, piglets are limited in the use of native Zn because of the antagonism of non-hydrolyzed dietary phytate. This explains the higher efficacy of phytase in improving Zn availability in this specie.

Possibility of alveolar bone promoting enhancement by using lipophilic and/or hydrophilic zinc related compounds in zinc-deficient osteoporosis rats.

The purpose of this research is improvement of therapeutic treatment for periodontitis by using lipophilic and/or hydrophilic zinc materials. The sample suspension injections were prepared from zinc octanate (C8Zn), zinc stearate (C18Zn), zinc sulfate hepta-hydrate (ZnSO4) and tricalcium phosphate (ZnTCP) containing 6.17 w/w% zinc. After administrating of all injections to around alveolar bone of zinc-deficient osteoporosis rats, plasma Zn concentration, bone mineral content (BMC) of jawbone, BMC and bone mechanical strength (BMS) of femur and permeability tests for hairless rat stripped skin were measured as therapeutic scores. BMC and BMS were measured by using an X-ray computing tomography and the three-point bending method, respectively. The body weight, plasma Zn concentrations and the area under curve (AUC) for Zn of C8Zn, C18Zn and ZnTCP group rats were higher than those of control group, but those of ZnSO4 group were not changed. BMC of alveolar bone and femur and BMS of femur for C8Zn and C18Zn groups for 12 weeks were significantly higher than those of the control group, but those of ZnSO4 group were not changed. Stripped rat skin permeability treated by the hydrophilic creams containing C8Zn was 5-times higher than that of ZnTCP.

The relation between keratoconus and plasma levels of MMP-2, zinc, and SOD.

PURPOSE: To evaluate the levels of matrix metalloproteinase-2 (MMP-2), superoxide dismutase (SOD), and zinc in plasma taken from patients with keratoconus and to investigate the likely association between these factors and keratoconus. METHODS: A total of 36 patients with keratoconus and 40 control subjects at the Department of Ophthalmology, Faculty of Medicine, Gaziosmanpasa University, were included in the study. Plasma levels of zinc were determined with atomic absorption spectrometry for all the subjects. Measurements of plasma MMP-2 levels were performed by the enzyme-linked immunosorbent assay method. Total plasma (Cu/Zn and Mn) SOD activity was also determined photometrically. RESULTS: The plasma concentrations of zinc and MMP-2 were significantly lower in patients with keratoconus than in the healthy controls (P < 0.001). Total plasma SOD levels were significantly higher in patients with keratoconus than in the healthy controls (P < 0.001). CONCLUSIONS: We detected reduced plasma levels of zinc and MMP-2, and enhanced plasma levels of SOD in patients with keratoconus compared with the healthy subjects. The data presented provide insight into the potential role these molecules may play in the etiopathogenesis of this disease.

Zinc supplementation in children with acute diarrhoea.

BACKGROUND: In Nigeria, diarrhoeal disease is second only to malaria as a cause of death the under 5 age group. This study was aimed at assessing the benefit or otherwise of zinc supplement in acute diarrhoea. SUBJECTS AND METHODS: This was a multi-centred randomized double blind controlled study. Children with acute diarrhoea aged between 6 and 24 months were randomized into zinc supplemented and placebo groups. Plasma zinc levels were analyzed at enrollment and at the end of the study. The children were reviewed for the next three months from the time of enrollment. RESULTS: The mean plasma zinc levels at baseline and at the end of the study were 0.06 +/- 0.04 and 0.067 +/- 0.03 ppm in the zinc supplemented group and 0.11 +/- 0.02 and 0.05 +/- 0.03 ppm in the control group. The differences were not statistically significant. The zinc supplemented group had an average weight gain of 1.1 kg as against 0.73 kg (p = 0.00) for the control group in the study period. No adverse effect was reported on account of zinc supplementation. CONCLUSION: Zinc supplementation is beneficial in acute diarrhoea as observed in this study.

Serum zinc levels in celiac disease.

This study was done to determine the zinc levels in 30 children with celiac disease. Serum zinc level was estimated at inclusion and zinc supplementation was given for 3 months. Zinc levels were repeated at 3 and 6 months after inclusion. The serum zinc levels of newly diagnosed CD cases (0.64+/-0.34 microg/mL) versus controls (0.94+/-0.14 microg/mL) were significantly lower (95% CI -0.44 to -1.4), whereas in the old cases this difference was non-significant. The serum zinc level among severely malnourished and stunted celiac cases was also significantly lower irrespective of their treatment status. We conclude that serum zinc levels are low in newly diagnosed and severely malnourished children with celiac disease.

Metallothionein, zinc, and mercury levels in tissues of young rats exposed to zinc and subsequently to mercury.

Several studies have described mercury toxicity and the role of metallothioneins (MT) in the detoxification and regulation of metal homeostasis. However, little data exist on this topic during the specific post-natal developmental phase in young mammals. This developmental phase is particularly important since young animals are more sensitive to toxicants than adults. The objective of this work was to investigate whether MT participates in the mechanism of protection conferred by zinc pre-treatment on the toxic effects induced by mercury in neonate rats. Pups were exposed to ZnCl(2) (5 doses of 27 mg/kg/day, s.c.) and subsequently to HgCl(2) (5 doses of 5 mg/kg/day, s.c.); metal (Zn and Hg) and MT contents were analyzed in the liver, kidney, and blood. MT was induced in the liver and kidney of pups of both Zn-sal and Zn-Hg groups, although the greatest increase was in neonates exposed to Zn only. A direct relationship exists between MT and metals for both hepatic and renal tissues, which indicates that the increase in metal levels occurs in parallel to the increase in MT content. Although the heat-treated cytosolic fraction is rich in MT and metals, higher Zn and Hg contents were detected in the insoluble fraction of all tissues. These results suggest that MT is, at least in part, responsible for preventing Hg accumulation in the liver and blood and decreasing renal toxicity.

Antepartum/postpartum depressive symptoms and serum zinc and magnesium levels.

In the present study, we investigated the relationship between depressive symptoms and serum zinc and magnesium level in antepartum and postpartum women. All women received standard vitamin, zinc and magnesium supplementation. Sixty-six pregnant women in the Czerwiakowski Hospital in Kraków were assessed for prepartum depressive symptoms using the Beck Depression Inventory (BDI). Sixty-two and fifty-eight women were also assessed for postpartum depressive symptoms (using Edinburgh Postnatal Depression Rating Scale, EPDRS) at 3 and 30 days after delivery, respectively. Serum zinc and magnesium levels were also determined at these time points, however, the number of examined subjects were diminished. A significantly higher EPDRS score (by 45%), indicating severity of depressive symptoms, was found on the 3rd day after childbirth compared with the 30th postpartum day. Moreover, the early post-delivery period (3rd day) was characterized by a 24% lower serum zinc concentration than that found on the 30th day after childbirth. BDI scores assessed a month before childbirth revealed mild depressive symptoms, which was accompanied by a serum zinc concentration similar to that found on the 3rd day after delivery. No significant alterations were found in the magnesium levels between these time points. The present results demonstrated a relationship between severity of depressive symptoms and decreased serum zinc (but not magnesium) concentration in a very specific type of affective disorder, the postpartum depression.

A semi-parametric method for describing the age-specific distribution of clinical measurements in cross-sectional study.

Age-specific distribution of clinical measurements in cross-sectional study is described in this paper. Since the distribution of measurements usually varies with age, a model with an age-dependent structure is needed. We propose here a statistical method for describing the age-specific distribution using an extension of the power-normal-model. The age-dependent parameters are to be estimated through a nonparametric smoothing technique based on the local likelihood method. As a consequence, we can compute a smoothed percentile curve of measurements with reference to age. Several kinds of clinical measurements are analyzed to determine the proposed method.

Zinc-mediated reduction of apoptosis in cardiac allografts.

BACKGROUND: Apoptosis is thought to occur during immune-mediated acute rejection of cardiac allografts. In vitro studies have shown that zinc inhibits the activity of the proapoptotic enzyme caspase-3. We hypothesized that ZnCl(2) would reduce acute cardiac rejection in vivo via the blockade of caspase-3-dependent apoptosis. (99m)Tc-labeled annexin V was used to measure apoptosis in cardiac allografts through nuclear imaging. Annexin V binds to phosphatidylserines, which are externalized to the outer membrane of apoptotic cells. METHODS AND RESULTS: Twenty-seven PVG rat hearts were transplanted heterotopically into the abdomen of untreated ACI rats as controls (group 1). Fifteen were scanned and euthanized on postoperative day 4, and 12 were assessed for graft survival. Group 2 and 3 rats (n=15 each) received 1 and 5 mg/kg ZnCl(2) BID IP, respectively. Nine of each of these groups were scanned and euthanized on postoperative day 4, and 6 were studied for allograft survival. Group 4 rats (n=3) received isografts. Region-of-interest analysis demonstrated a dose-dependent reduction in (99m)Tc annexin uptake in ZnCl(2)-treated allografts: 2.43+/-0.37% for group 1, 1. 97+/-0.41% for group 2, 1.21+/-0.47% for group 3, and 0.55+/-0.19% for group 4 (ANOVA, P:=0.001). Graft survival times of 6.4+/-1.7, 9. 3+/-3.0, and 11.5+/-3.4 days for groups 1, 2, and 3, respectively, were also observed (ANOVA, P:=0.001). Caspase-3 activity in the allografts showed a 3.7-fold reduction in group 3 animals compared with group 1 animals (P:=0.004). CONCLUSIONS: Apoptosis that occurs in acute cardiac allograft rejection is reduced with ZnCl(2) in a dose-dependent manner via caspase-3 inhibition.

An in vivo study of the gastrointestinal absorption site for zinc chloride in mice.

The experimental model presented below enables quantitation of the uptake of zinc (Zn++) into gastrointestinal mucosal cells in vivo using gamma-counting of 65Zn. Experiments were performed in mice fed their normal diet under natural physiological conditions. The in vivo site(s) of significant zinc absorption may thereby be identified. Absorption of zinc was extensive during the first hour after administration of a single oral dose of ZnCl2. Apparently, absorption continued during at least eight hours postdosage, and probably continued for 48 hours. The intestinal mucosal labelling profile for zinc did not depend on dose size or the mode of administration (single oral doses or in drinking water). The duodenum and ileum were important sites for rapid zinc absorption. A continuous, slower absorption of zinc may take place in the jejunum. The stomach, caecum and colon appeared to be insignificant sites of zinc absorption. The transit time for zinc was very short as large quantities of zinc passed through the small intestine within one hour. In contrast to other studies, the intestinal labelling profile or the extent of zinc absorption were not changed in mice that received Tetraethylthiuram disulfide (TTD) in their food.

Interrelación del hierro, selenio y zinc en sangre y pelo de caballos con el tiempo de recuperación cardiaca después del ejercicio / Interelation between selenium, iron and zinc contents in blood and hair of horses to heart recuperation time after physical excercise

La interrelación del número de latidos cardiacos del animal con el contenido sanguíneo de Se, Fe y Zn permitirá a través de la medición de estos últimos predecir la capacidad cardiaca de trabajo que son los objetivos de la presente investigación. Esta investigación se llevó a cabo en diez caballos criollos de 450 kg de peso y 11 años de edad. Los resultados promedio de análisis fueron: 73 ng de Se/ml, 52.3 µg de Fe/ml y 3.5 µg de Zn/ml de sangre y 440 ng de Se/g, 3.8 µg de Fe/g y 9.3 µg de Zn/g de pelo. El promedio de la frecuencia cardiaca fue de 37 latidos por minuto. El tiempo promedio de recuperación de las constantes fisiológicas a sus valores básales después del ejercicio fue de 37 minutos. Se encontró que los caballos que presentan concentraciones de 115 ng/ml de Se y 62 µg de Fe/ml, de sangre tienen una más pronta recuperación (20 min) de las constantes cardiacas después del ejercicio, pero el Zn no tuvo un índice de correlación significativa. Cuando los caballos tuvieron 60 ng de Se y 49 µg de Fe/ml de sangre, el tiempo de recuperación fue a los 40 min. El índice de correlación entre el contenido de Se y Fe sanguíneo y el tiempo de reucperación fue de -0.84 y de -0.71, respectivamente, lo que indica que cuando más altos sean los niveles de estos elementos el tiempo de recuperación será más corto. Las correlaciones del contenido de los elementos en el pelo con el tiempo de recuperación cardiaca no fueron significativas. De acuerdo a estos resultados, el Se y Fe sanguíneo se pueden usar como parámetros para conocer la capacidad de recuperación después del ejercicio

Mangafodipir trisodium injection, a new contrast medium for magnetic resonance imaging: detection and quantitation of the parent compound MnDPDP and metabolites in human plasma by high performance liquid chromatography.

Manganese(II) dipyridoxyl diphosphate (MnDPDP) is the active component of mangafodipir trisodium injection (Teslascan), a new contrast medium for magnetic resonance imaging. A high performance liquid chromatography (HPLC) method was developed for the simultaneous determination of MnDPDP and its five major metabolites in human plasma, i.e. the dephosphorylation products MnDPMP (manganese(II) dipyridoxyl monophosphate) and MnPLED (manganese(II) dipyridoxyl ethylenediamine diacetate) and the corresponding substances obtained after transmetallation with zinc (ZnDPDP, ZnDPMP and ZnPLED). Heparinized blood samples from patients receiving mangafodipir trisodium injection were immediately mixed with solid trisodium phosphate dodecahydrate to obtain pH 10.0 +/- 0.2 in order to inhibit further in vitro dephosphorylation and transmetallation. The plasma thus obtained was ultrafiltrated prior to HPLC analysis. The chromatographic separation was obtained using a mixed-bed resin with both anion exchange and reversed-phase functions (OmniPac PAX-500) using isocratic elution and UV detection at 310 nm. With an injection volume of 50 microliters, the limit of quantitation (LOQ) values were 0.8-2.3 microM for the Mn compounds and 0.1-0.8 microM for the Zn compounds. The between-run accuracy of spiked plasma samples was in the range 97.5-106.7% with a precision in the range 3.1-9.0%. The best fit calibration curves were obtained using non-linear regression according to the equation Y = A + BXM in the concentration range from LOQ to 100 microM. Long-term storage of spiked plasma samples for three months at -20 degrees C demonstrated the required stability with recovery values within 85-115% of MnDPDP and its five metabolites.