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Effect of treatment with zinc gluconate or zinc acetate on experimental and natural colds.

Two clinical trials were conducted, one involving 273 subjects with experimental rhinovirus colds and the other involving 281 subjects with natural colds. Symptomatic volunteers were randomized to receive oral lozenges containing zinc gluconate (13.3 mg), zinc acetate (5 or 11.5 mg), or placebo. The median duration of illness in zinc gluconate recipients was 2.5 days, contrasted with 3.5 days in the placebo recipients (P=.035), in the experimental colds study. Zinc gluconate had no effect on symptom severity and zinc acetate had no effect on either duration or severity. Neither formulation had an effect on the duration or severity of natural cold symptoms. Evaluation of blinding, taste, and adverse events revealed no significant differences among the 4 treatment arms. Zinc compounds appear to have little utility for common-cold treatment.

Adolescent↗

Acute zinc intoxication: comparison of the antidotal efficacy of several chelating agents.

Four zinc compounds (acetate, nitrate, chloride and sulfate) were administered po or ip to rats and mice. The LD50 values were determined. Animals were observed for 14 days. The majority of deaths occurred during the first 48 hr. The clinical and physical signs appearing after intoxication included miosis, conjunctivitis, decreased food and water consumption and hemorrhages and hematomas in the tail. These changes decreased with time which would suggest a quick elimination of zinc. To determine the effect of 6 chelating agents on the toxicity of zinc, various doses of zinc acetate (66-330 mg/kg) were given ip to male mice followed by the injection of one of the chelators. DTPA, D-PA, CDTA and EDTA were the most effective. CDTA and DTPA were also the most effective in increasing the urinary excretion of zinc. DTPA appears to be the most effective agent of those tested in the prevention of acute zinc intoxication. However, CDTA may be considered as a possible alternative.

Animals↗

Preventive effect of zinc acexamate administration in streptozotocin-diabetic rats: Restoration of bone loss.

The preventive effect of zinc compounds on bone loss in streptozotocin (STZ)-diabetic rats was investigated. Rats received a single subcutaneous administration of STZ (6.0 mg/100 g body weight), and 7, 14 or 21 days later the animals were sacrificed by bleeding. STZ administration caused a significant decrease in body weight and a significant increase in serum glucose and triglyceride levels, indicating diabetic condition. Femoral-diaphyseal and -metaphyseal alkaline phosphatase activity, calcium and deoxyribonucleic acid (DNA) contents were significantly decreased by STZ administration, showing that diabetic condition causes bone loss. Zinc sulfate (2.5 mg Zn/100 g) or zinc acexamate (2.5 mg Zn/100 g) was orally administered once daily for 14 days to rats received a single subcutaneous administration of STZ (6.0 mg/100 g). STZ administration-induced increase in serum glucose and triglyceride levels and decrease in body weight, femoral-diaphyseal and -metaphyseal alkaline phosphatase activity, DNA and calcium contents were significantly prevented by the administration of zinc acexamate. The preventive effect of zinc sulfate on bone components was not seen. The present results demonstrate that the administration of zinc acexamate has a preventive effect on bone loss in STZ-diabetic rats in vivo.

Alkaline Phosphatase↗

[Zinc: concepts on an essential micronutrient].

It is now well known that zinc is an essential micronutrient. Even though much information is available, there are many points that remain to be studied. zinc is absorbed by the intestine and transported in the plasma by albumin, forming a small exchangeable pool, which is rapidly exhausted even in cases of mild deficiency. zinc is essential for the activity of about 70 enzymes among other functions. Therefore, zinc deficiency produces a great number of clinical disorders, the symptoms of which may range between mild up to serious dysfunctions. These problems are corrected by a dietary supplementation with zinc. The lack of a reliable method to determine the zinc nutritional status reflects the problem to estimate the metal recommended dietary allowances, which are difficulty met specially by children, old persons and pregnant women which constitute the main risk groups. Although our knowledge concerning zinc toxicity is scarce, it is well known that the amounts of zinc that produces toxic effects are much higher than those that are contained in regular diets as well as in diets supplemented with this metal. Therefore, the need of the development of effective strategies, like food fortification with proper zinc compounds, appears as an attractive alternative in order to prevent and/or correct the deficiency of this vital element and to improve the health and the life quality of the whole population.

Age Factors↗

[Anticalculus dentifrices. A new era in preventive dentistry?].

Anticalculus toothpastes are available on the market. Toothpastes with Zinc compounds interfere mainly with the plaque formation. Dentifrices containing pyrophosphate give the highest reductions in calculus formation. The inclusion of pyrophosphate in a fluoride containing dentifrice did not interfere with the cariostatic action of fluoride on tooth enamel. The influence of anticalculus dentifrices on root caries and root hypersensitivity are, so far, not documented. Fundamentally, a lot of doubt still exists about the precise role of supragingival calculus formation in the onset of periodontal disease.

Dental Calculus↗

The reaction between ZnO and molten Na2S2O7 or K2S2O7 forming Na2Zn(SO4)2 orK2Zn(SO4)2, studied by Raman spectroscopy and x-ray diffraction.

Reactions between solid zinc oxide and molten sodium or potassium pyrosulfates at 500 degrees C are shown by Raman spectroscopy to be 1:1 reactions leading to solutions. By lowering the temperature of the solution melts, colorless crystals form. Raman spectra of the crystals are given and tentatively assigned. Crystal structures of the monoclinic salts at room temperature are given. Na(2)Zn(SO(4))(2): space group = P2/n (No. 13), Z = 8, a = 8.648(3) Angstroms, b = 10.323(3) Angstroms, c = 15.103(5) Angstroms, beta = 90.879(6) degrees, and wR(2) = 0.0945 for 2748 independent reflections. K(2)Zn(SO(4))(2): space group = P2(1)/n (No.14), Z = 4, a = 5.3582(11) Angstroms, b = 8.7653(18) Angstroms, c = 16.152(3) Angstroms, beta = 91.78(3) degrees , and wR(2) = 0.0758 for 1930 independent reflections. In both compounds, zinc is nearly perfectly trigonally bipyramidal, coordinated to five oxygen atoms, with Zn-O bond lengths ranging from 1.99 to 2.15 Angstroms, equatorial bonds being slightly shorter on the average. The O-Zn-O angles are approximately 90 degrees and 120 degrees . The sulfate groups connect adjacent Zn(2+) ions, forming complicated three-dimensional networks. All oxygen atoms belong to nearly perfect tetrahedral SO(4)(2-) groups, bound to zinc. No oxygen atom is terminally bound to zinc; all zinc oxygens are further connected to sulfur atoms (Zn-O-S bridging). In both structures, some oxygen atoms are uniquely bound to certain S atoms. The sulfate group tetrahedra have quite short (1.42-1.45 Angstroms) terminal S-O bonds in comparison to the longer (1.46-1.50 Angstroms) Zn-bridging S-O bonds. The Na(+) or K(+) ions adopt positions between the ZnO(5) hexahedra and the SO(4) tetrahedra, completing the three-dimensional network of the M(2)Zn(SO(4))(2) structures. Bond distances and angles compare well with literature values. Empirical correlations between S-O bond distances and average O-S-O bond angles follow a previously found trend.

Journal Article↗

Synthesis and characterization of quasi-two-coordinate transition metal dithiolates M(SAr*)2 (M = Cr, Mn, Fe, Co, Ni, Zn; Ar* = C6H3-2,6(C6H2-2,4,6-Pri3)2.

A sequence of first row transition metal(II) dithiolates M(SAr)(2) (M = Cr(1), Mn(2), Fe(3), Co(4), Ni(5) and Zn(6); Ar = C(6)H(3)-2,6-(C(6)H(2)-2,4,6-Pr(i)(3))(2)) has been synthesized and characterized. Compounds 1-5 were obtained by the reaction of two equiv of LiSAr with a metal dihalide, whereas 6 was obtained by treatment of ZnMe(2) with 2 equiv of HSAr. They were characterized by spectroscopy, magnetic measurements, and X-ray crystallography. The dithiolates 1, 2, and 4-6 possess linear or nearly linear SMS units with further interactions between M and two ipso carbons from C(6)H(2)-2,4,6-Pr(i)(3) rings. The iron species 3, however, has a bent geometry, two different Fe-S distances, and an interaction between iron and one ipso carbon of a flanking ring. The secondary M-C interactions vary in strength in the sequence Cr(2+) approximately Fe(2+) > Co(2+) approximately Ni(2+) > Mn(2+) approximately Zn(2+) such that the manganese and zinc compounds have essentially two coordination but the chromium and iron complexes are quasi four and three coordinate, respectively. The geometric distortions in the iron species 3 suggested that the structure represents the initial stage of a rearrangement into a sandwich structure involving metal-aryl ring coordination. The bent structure of 3 probably also precludes the observation of free ion magnetism of Fe(2+) recently reported for Fe{C(SiMe(3))(3)}(2). DFT calculations on the model compounds M(SPh)(2) (M = Cr-Ni) support the higher tendency of the iron species to distort its geometry.

Journal Article↗

Comparison of measured dermal dust exposures with predicted exposures given by the EASE expert system.

Estimation and Assessment of Substance Exposure (EASE) is a rule-based computer expert system used by regulatory authorities within the European Union to assist in assessing exposure for both new and existing substances. It can provide estimates of both inhalation exposure levels and dermal exposure levels to the hands and forearms. This article describes the results of a study in which measurements of workplace dermal zinc exposures were collected for an industry-wide risk assessment and also compared with the levels predicted by EASE. Measurements were obtained from subjects in seven different workplaces that were producing or working with zinc metal or zinc compounds. The work activities were grouped a priori into one of three categories used by EASE for dermal exposure assessment: 'non-dispersive use with intermittent direct handling', 'wide dispersive use with intermittent direct handling' and 'wide dispersive use with extensive direct handling'. The predicted exposure ranges for these categories are 0.1-1, 1-5 and 5-15 mg cm(-2) day(-1). Although the average measured exposure levels for each of the categories increased in line with the predictions from EASE, the model overestimated dermal exposure to the hands by a factor of approximately 50 when the mid-point of the EASE range was compared with the measured mean exposure. Furthermore, a significant additional exposure was found on other parts of the workers' bodies for which EASE does not provide any estimates. Interpretation of the dermal exposure data was complicated by the use of protective gloves, which might have limited the amount of zinc dust adhering to the workers' skin. However, observation of the work activities suggested that the pattern of glove use was such that they would not provide a consistent level of protection. This study provided an opportunity to collect a large amount of dermal zinc exposure data for risk assessment purposes and also enabled a dermal sampling method to be developed and assessed. There is no standard method for dermal dust exposure measurement, and the choice of method was a key factor in the exposure estimation process. With regard to comparison with the EASE predictions, it is possible that EASE could appear to perform more accurately if its predictions were compared with measurements obtained using surrogate skin sampling methods. However, we believe that such sampling can provide a gross overestimate of the dust on the skin surface. We suggest that further development of the EASE system is necessary to ensure that it better reflects whole-body dermal exposures to dusts.

Dermis↗

The use of (14)C tracer technique to assess the functional response of zooplankton community grazing to toxic impact.

The use of functional endpoints in risk assessment of pollutants for marine pelagic communities is scarce, especially for the function of zooplankton communities. This work presents a rapid, inexpensive and ecologically relevant technique to assess the effect of toxic compounds on the grazing rates of zooplankton communities. The combination of a (14)C-tracer labelling technique with a fast (< 3 h) and representative sub-sampling and handling makes it possible to measure changes in food uptake of freshly collected natural zooplankton communities in a short-term assay. The methodology is described and its validity is determined by a full account of the fate of isotope tracers (up to 15% taken up by zooplankton). Egg production of Acartia tonsa cultures exposed to DCOI yielded EC(50) values of 118+/-33 nM DCOI after three days, where EC(50) values from grazing of natural zooplankton communities was 136+/-29 nM DCOI, indicating that grazing was the more sensitive variable. Finally the method was tested in a mesocosm experiment designed to evaluate the toxicity of the antifouling compound zinc pyrithion (ZPT) with an EC(50) value of 17 nM ZPT (SD=3.3 nM, n=3). The method was found to be reproducible both at the community (CV=8-39%) and individual level (CV=23-53%), and could detect small changes in response to a toxicant in a natural pelagic system. The use of natural communities in combination with the fast and cost-effective procedure makes this technique a powerful tool in risk assessment, where lack of ecological relevance or reproducible results often results in unwanted high uncertainties.

Animals↗

Leaching with Penicillium simplicissimum: Influence of Metals and Buffers on Proton Extrusion and Citric Acid Production.

In the presence of insoluble metal oxides (industrial filter dust, zinc oxide, synthetic mixture of metal oxides), Penicillium simplicissimum developed the ability to excrete considerable amounts of citric acid (>100 mM). Parallel with the increase of citric acid concentration in the culture broth, zinc was solubilized from zinc oxide. The adsorption of filter dust onto the mycelium (the pellets formed were less than 1 mm in diameter) was required for not only the citric acid excretion but also the leaching of zinc. When the filter dust was replaced with a synthetic mixture of metal oxides or with zinc oxide in combination with trace elements, levels of adsorption and citric acid production were observed to be similar to those in experiments where industrial filter dust was used. The two most important properties of the filter dust were its heavy-metal content and its buffering capacity. These properties were simulated by adding heavy metals in soluble form (as chlorides, sulfates, or nitrates) or soluble buffers to the medium. Both heavy metals and buffers were not able to induce a citric acid efflux. As with citric acid production by Aspergillus niger, the addition of manganese lowered citric acid excretion (by 40% with metal oxide-induced citric acid efflux and by 100% with urea-induced citric acid efflux). Copper antagonized the effect of manganese. The mechanism for the bulk of citric acid excretion by P. simplicissimum, however, seemed to be different from that described for citric acid accumulation by A. niger. Because of the inefficiency of metals in solubilized form and of soluble buffers to induce a strong citric acid efflux, adsorption of an insoluble metal compound (zinc oxide) turned out to be essential. Surface phenomena possibly involving the plasma membrane H-ATPase are thought to participate in the induction of citric acid excretion by P. simplicissimum in the presence of industrial filter dust.

Journal Article↗

Optimum formulation for sustained-release insulin.

Our aim was to prepare an optimum formulation for a sustained-release preparation of insulin using biodegradable polymer composed of co-poly(D,L-lactic/glycolic) acids (PLGA)(L/G ratio: 50/50). Various kinds of PLGA microcapsules containing 3% insulin were administered subcutaneously (250 U/kg) as a single dose to rats with streptozotocin-induced diabetes, and plasma insulin levels were monitored. The following results were obtained. (1) Glycerin and water were suitable additives to prepare a reproducible injectable formulation. (2) Addition of zinc compounds was essential to diminish rapid insulin release and six-fold molar excess of ZnO to insulin was desirable. (3) The size of insulin particles showed the following order: human insulin > lyophilized human insulin > Zn-free human insulin. Zn-free insulin was similar to lyophilized insulin with respect to control of rapid release, so a smaller particle size was essential. (4) The size of the microcapsules also affected the release of insulin. With larger microcapsules (approximately 30 microm), there was gradual release and a significant second phase of insulin release, while smaller microcapsules did not allow sustained release. Some variation in microcapsule size contributed to more constant and sustained release. (5) Based on the insulin release profile in vivo, a suitable molecular weight for PLGA was around 6000. The biological activity of insulin extracted from the formulation was similar to that of normal insulin. These experiments allowed us to prepare a desirable sustained-release insulin formulation.

Animals↗