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Zinc deficiency causes dysgeusia and dermatitis as well as anemia. As approximately half of dialysis patients have zinc deficiency, zinc supplementation should be considered in case of erythropoiesis-stimulating agent (ESA)-hyporesponsive anemia. We report a case of a chronic dialysis patient with copper deficiency anemia caused by standard-dose zinc supplementation. The patient was a 70-year-old woman who had received maintenance hemodialysis for 8 years due to diabetic nephropathy. She had been treated with weekly administration of darbepoetin 30 μg for renal anemia, which resulted in Hb 12 to 14 g/dL. She had no dysgeusia. When zinc deficiency (44 μg/dL) had been identified 4 months earlier, 50 mg daily zinc acetate hydrate (Nobelzin®), which is the standard dose, was started. Unexpectedly, her anemia progressed slowly with macrocytosis together with granulocytopenia. Her platelet count did not decrease at that time. Laboratory tests revealed a marked decrease of serum copper (< 4 μg/dL) and ceruloplasmin (< 2 mg/dL), although serum zinc was within the normal limit (125 μg/dL). We discontinued zinc acetate and started copper supplementation including cocoa for 1 month. Her anemia and granulocytopenia were dramatically restored coincident with the increase in both serum copper and ceruloplasmin. Copper supplementation also improved her iron status as assessed by transferrin saturation and ferritin. Clinicians should monitor both zinc and copper status in anemic dialysis patients during zinc supplementation, as both are important to drive normal hematopoiesis., Competing Interests: Declarations. Conflict of interest: The authors declare that they have no conflict of interests. Ethical approval and consent to participate: The ethical committee of Kitano Hospital approved this case report. Consent for publication: Informed consent was obtained from the patient in this case report., (© 2024. The Author(s), under exclusive licence to Japanese Society of Nephrology.)

Background: This study aimed to compare the effects of three mucoadhesive gels containing lidocaine, zinc acetate, and tannic acid on the gag reflex of dental patients., Methods: This randomized double-blind clinical trial was conducted on 228 dental patients with gag reflex. The patients were randomly assigned to four groups (n = 57) of placebo, 2% lidocaine, 2% tannic acid, and 2% zinc acetate. The severity of the gag reflex of patients was initially scored by stimulating their soft and hard palate with a radiographic film using a 0-5 visual analog scale. After 5 min, mucoadhesive gels containing 2% lidocaine, zinc acetate, or tannic acid were applied on the hard and soft palate for 5-10 min, and the severity of the gag reflex was scored again. Data were analyzed by ANOVA and paired t-test for the single group comparison (alpha = 0.05)., Results: The four groups had no significant difference in the baseline mean gag score (p = 0.05). The difference in the mean gag score was significant among the four groups after the intervention (p < 0.00), and the mean score in the experimental groups was significantly lower than that in the placebo group (p < 0.00). The difference in the mean gag score was not significant between the experimental groups (p > 0.05)., Conclusions: The mucoadhesive gels containing 2% lidocaine, tannic acid, or zinc acetate significantly decreased the gag reflex in dental patients, with all three treatments showing comparable efficacy compared to the placebo. These findings suggest that each gel formulation is a viable alternative for managing the gag reflex during dental procedures., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the ethics committee of the university (IR.KUMS.REC.1401.384). All methods were carried out in accordance with relevant guidelines and regulations. Written informed consent was obtained from all patients. The inclusion criteria were having age over 18 years, and willingness for participation in the study and signing informed consent forms. Consent for publication: Identified images or other personal or clinical details of participants are not presented in this manuscript. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Chikungunya virus (CHIKV), which causes chikungunya fever, is an arbovirus of public health concern with no approved antiviral therapies. A significant proportion of patients develop chronic arthritis after an infection. Zinc and magnesium salts help the immune system respond effectively against viral infections. This study explored the antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV infection., Methods: The highest non-toxic concentration of the salts (100 µM) was used to assess the prophylactic, virucidal, and therapeutic anti-CHIKV activities. Dose-dependent antiviral effects were investigated to find out the 50% inhibitory concentration of the salts. Entry bypass assay was conducted to find out whether the salts affect virus entry or post entry stages. Virus output in all these experiments was estimated using a focus-forming unit assay, real-time RT-PCR, and immunofluorescence assay., Results: Different time- and temperature-dependent assays revealed the therapeutic antiviral activity of zinc and magnesium salts against CHIKV. A minimum exposure of 4 hours and treatment initiation within 1 to 2 hours of infection are required for inhibition of CHIKV. Entry assays revealed that zinc salt affected virus-entry. Entry bypass assays suggested that both salts affected post-entry stages of CHIKV. In infected C57BL6 mice orally fed with zinc and magnesium salts, a reduction in viral RNA copy number was observed., Conclusion: The study results suggest zinc salts exert anti-CHIKV activity at entry and post entry stages of the virus life cycle, while magnesium salt affect CHIKV at post entry stages. Overall, the study highlights the significant antiviral potential of zinc sulphate, zinc acetate, and magnesium sulphate against CHIKV, which can be exploited in designing potential therapeutic strategies for early treatment of chikungunya patients, thereby reducing the virus-associated persistent arthritis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Davuluri, Shukla, Kakade, Cherian, Alagarasu and Parashar.)

Recently the complexation-mediated antioxidative and glycaemic control synergism between zinc(II) and caffeic acid was demonstrated in vitro. The present study evaluated the complexation-mediated antidiabetic and antioxidative synergism between zinc(II) and caffeic acid in diabetic rats and the possible underlying mechanisms. Male SD rats were induced with diabetes using 10% fructose and 40 mg/kg bw streptozotocin. The diabetic rats were treated with Zn(II)-caffeic acid complex and its precursors (caffeic acid and zinc acetate) for 4 weeks at predetermined doses. The effect of the treatments on diabetes and oxidative stress was measured. The complex ameliorated diabetic alterations. It reduced polyphagia and polydipsia and recovered weight loss. It increased insulin secretion, insulin sensitivity, hepatic and muscle glycogen, muscle hexokinase activity and Akt phosphorylation, which resulted in improved glucose tolerance and reduced blood glucose in the diabetic rats. The complex concomitantly reduced systemic and tissue lipid peroxidation and increased antioxidant enzymes activity in the diabetic rats. The complex outperformed the antidiabetic and antioxidative action of its precursors and had a broader bioactivity profile. Complexing zinc acetate with caffeic acid improved their ameliorative effect on insulin resistance by ∼24% and 42%, respectively, as well as their anti-hyperglycaemic action by ∼24 - 36% and ∼42 - 47%, respectively, suggesting a complexation-mediated synergism. In some instances, the antidiabetic action of the complex was comparable to metformin, while its antioxidant effect was better than that of metformin. Zinc(II)-caffeic acid complexation may be an alternative approach to improving the efficacy of antidiabetic and antioxidative therapy with minimal adverse or side effects., Competing Interests: Conflict of interest statement All authors declare that they have no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Dysgeusia is a relatively early symptom of zinc deficiency, and zinc replacement is effective in treating dysgeusia. The administration of zinc acetate hydrate (ZAH) was approved in 2017 for patients with hypozincemia in Japan. This retrospective study was conducted to explore the efficacy and safety of ZAH administration in patients with hypozincemia-induced dysgeusia., Methods: Patients with hypozincemia-induced dysgeusia who visited our hospital from May 2013 to December 2019 were included in this study. ZAH (zinc content; 50 mg/day) was administered to 42 patients for 24 weeks. The taste test was performed using the filter paper disk method, and the total cognitive thresholds of the left and right chorda tympani regions were used. Changes in taste function, serum zinc and copper levels, and copper/zinc ratio were analyzed. A total of 28 patients who received polaprezinc (PPZ, zinc content; 34 mg/day) for 24 weeks, who were prescribed until ZAH was approved, were registered as controls., Results: Serum zinc levels at 12 and 24 weeks after ZAH or PPZ administration were higher than those before administration. These levels were significantly higher in the ZAH-treated group than in the PPZ-treated group. However, serum copper levels did not significantly change before and after administration. In the taste test, the taste thresholds for the acidity and salty at 12 and 24 weeks after ZAH administration were significantly decreased compared to before administration. In contrast, in the PPZ group, the taste thresholds for the acidity and salty were significantly decreased 24 weeks after administration., Conclusions: ZAH (50 mg/day) administration was effective in improving the gustatory sensitivity of patients with dysgeusia and hypozincemia 12 weeks after administration without affecting the serum copper level. ZAH was also more effective than PPZ., (© 2023. The Author(s).)

Zinc is an essential trace element for the maintenance of life because it acts as a center of activity or cofactor for hundreds of enzymes. Zinc deficiency causes a variety of symptoms, including anemia, dermatitis, stomatitis, alopecia, bedsores, decreased appetite, impaired growth, gonadal dysfunction, susceptibility to infection, and taste disorders, etc. In March 2017, zinc acetate hydrate, which had been approved for Wilson disease in Japan, received an additional indication for hypozincemia. Hypozincemia is frequently observed in patients with chronic liver disease (CLD), especially cirrhosis, and it has recently been shown that hypozincemia is closely related to the development of liver fibrosis and increased risk of liver carcinogenesis, in addition to the appearance of various subjective symptoms. Moreover, hypozincemia in CLD may be associated with sarcopenia (i.e., decrease in muscle strength and muscle mass) and frailty (i.e., vulnerability), which receive much attention these days. It is assumed that treatment with zinc acetate hydrate will become widespread in patients with CLD. Zinc acetate hydrate may also have potential for improving sarcopenia in patients with CLD. This review primarily outlines the significance of zinc in patients with CLD.

Purpose: Dysgeusia is an adverse event caused by chemotherapy. Although retrospective studies have shown zinc administration improves dysgeusia, there have been no prospective studies. The present study examined effects of zinc therapy on dysgeusia in patients with gastrointestinal cancer., Methods: This multicenter, prospective, observational study enrolled patients with dysgeusia during chemotherapy treatment. Patients received no intervention (control), polaprezinc p.o., or zinc acetate hydrate p.o., and serum zinc levels were measured at 0 (baseline), 6, and 12 weeks. Dysgeusia was assessed using CTCAE v5.0 and subjective total taste acuity (STTA) criteria using questionnaires at baseline and 12 weeks., Results: From February 2020 to June 2021, 180 patients were enrolled from 17 institutes. There were no differences in mean baseline serum zinc levels among the groups (67.3, 66.6, and 67.5 μg/dL in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. P = 0.846). The changes in mean serum zinc levels after 12 weeks were - 3.8, + 14.3, and + 46.6 μg/dL, and the efficacy rates of dysgeusia were 33.3%, 36.8%, and 34.6% using CTCAE and 33.3%, 52.6%, 32.7% using STTA in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. The STTA scores improved in all groups, with significant improvement observed in the polaprezinc group compared with the no intervention group (P = 0.045)., Conclusion: There was no significant correlation between the degree of serum zinc elevation and improvement in dysgeusia, suggesting that polaprezinc, but not zinc acetate hydrate, was effective in improving chemotherapy-induced dysgeusia., Trial Registration: UMIN000039653. Date of registration: March 2, 2020., (© 2022. The Author(s).)

With the increasing morbidity and mortality rates associated with multidrug-resistant bacteria, interest in bacteriophage therapy has been revived. However, bacterial resistance to phage infection threatens the usefulness of phage therapy, especially its inclusion in modern medicine. Multidrug-resistant Acinetobacter baumannii is a top-priority pathogen requiring urgent intervention and new therapeutic approaches, such as phage therapy. Here, we experimentally adapted A. baumannii WHG40004 to its lytic phage P21 and thereafter isolated a phage-resistant bacterial mutant, named Ev5-WHG. We then aimed to identify potential agents to aid phage killing of Ev5-WHG by analyzing its genome and that of the wild-type strain. The enriched Gene Ontology (GO) analysis based on genetic alterations in minor alleles and mutations showed that pathways such as zinc ion transport and cell membrane synthesis could play certain roles in phage resistance. Remarkably, the combination of zinc acetate and P21 showed increased bactericidal effect on Ev5-WHG. Significantly also, we showed that P21 completely prevented the growth of wild-type WHG40004 in the presence of antibiotics (meropenem and imipenem). The results from this study indicate that the analysis of phage resistance signatures during adaptation of bacteria to a lytic phage can inform the choice of agents to work cooperatively with phage to limit and/or reverse resistance. This approach could be important for guiding future successful phage therapy. IMPORTANCE Bacteriophages have proven very useful as alternative therapeutic agents in combating multidrug-resistant bacterial infections; however, bacterial resistance to phages threatens their use. In this study, we showed a new strategy of leveraging genetic signatures that accompany phage resistance in bacteria to predict agents that can be used with lytic phages to combat multidrug-resistant Acinetobacter baumannii. Significantly, this approach was helpful in suggesting the use of zinc acetate to reduce resistance in phage-resistant bacteria, as well as the use of phage with antibiotics meropenem and imipenem to prevent resistance in a wild-type strain of multidrug-resistant A. baumannii. The approach of this study will be helpful for improving the outcome of phage therapy and in overcoming antimicrobial resistance.

We aimed to determine the efficacy of zinc acetate hydrate (ZAH) treatment for hypozincemia in elderly inpatients and to identify the factors affecting its therapeutic effect. We enrolled 79 patients with a mean age of 82 years. The mean serum zinc level before ZAH administration was 53.4 ± 11.5 µg/dL. More than half of the patients (67%) had zinc deficiency (<60 µg/dL), whereas 33% had subclinical zinc deficiency (60-80 µg/dL). The median increase in serum zinc level per ZAH tablet (25 mg) was 1.00 µg/dL. Based on the cutoff value, two groups were identified: slight increase (<1.00 µg/dL) and marked increase (≥1.00 µg/dL) groups; the difference between the two groups was significant (0.57 ± 0.22 µg/dL, n = 39 vs. 1.68 ± 0.70 µg /dL, n = 40; p < 0.0001, Wilcoxon rank sum test). Logistic regression analysis using total zinc dose, serum albumin level, impaired renal function, and diuretics as multivariate variables revealed a significant difference in total zinc dose (total number of tablets per 25 mg tablet: odds ratio 1.056, 95% confidence interval 1.019-1.095, p = 0.003). A significant increase in serum zinc levels was observed in the group with a total zinc dose of less than 1000 mg. The results suggest that an increasing trend in total zinc dose is associated with a low increase in serum zinc levels. Therefore, for the treatment of zinc deficiency in elderly inpatients, serum zinc levels need to be measured once, at a total dose of 1000 mg after initiation of ZAH.

Purpose: To measure the serum levels of the oxidative stress markers superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx) and compare them before and after zinc supplementation in patients with early age-related macular degeneration (AMD). Methods: We measured serum zinc levels in 65 patients with early AMD. Of these, 29 patients with macular drusen and a serum zinc level <80 μg/dL received oral zinc acetate dihydrate (50 mg/day). Serum trace metal levels (zinc and copper) and oxidative stress marker levels (SOD, MDA, and GPx) were measured at baseline and 12 weeks after the treatment. The macular drusen areas and best-corrected visual acuity were evaluated in 24 participants who attended the 3-month follow-up. Results: MDA level was significantly decreased from baseline to 12 weeks after zinc administration (170.5 ± 100.9 vs. 148.3 ± 57.9 pmol/mL, P  = 0.03), while SOD was significantly increased from baseline to 12 weeks after zinc intake (4.2 ± 0.9 vs. 4.6 ± 0.9 U/mL, P  = 0.03). The serum zinc level was significantly correlated with the MDA level ( P  = 0.03, ρ = -0.26). The area of soft drusen was significantly decreased after zinc treatment (1,936,654.9 ± 1,348,267.6 vs. 966,883.9 ± 719,938.1 μmm 2 , P  = 0.04). Conclusions : The levels of oxidative stress markers MDA and SOD decreased and increased, respectively, after oral zinc administration to 24 patients with AMD. The therapeutic effect of zinc treatment on drusen area might differ depending on the drusen phenotype in early AMD.

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., (© 2019 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Objective: To examine a commercially available zinc acetate lozenge for treating the common cold., Design: Randomised, double-blinded, placebo-controlled trial., Setting: Working population in Finland., Participants: We included men and women aged ≥18 years who usually had ≥1 cold per winter. Exclusions were pregnancy, lactation, chronic runny nose or chronic cough., Intervention: We randomised 253 participants to receive a package of lozenges to be taken if they caught the common cold. Of the 253 participants, 88 contracted the common cold and 87 were included in our primary analysis. Zinc acetate lozenges contained 13 mg elemental zinc and placebo lozenges contained sucrose octa-acetate to camouflage the taste of zinc. Instruction to use was six times per day for the maximum of 5 days., Primary Outcome: Rate of recovery from the common cold analysed by Cox regression., Results: There was no difference in the recovery rate between zinc and placebo participants during the 10-day follow-up (rate ratio for zinc vs placebo=0.68, 95% CI 0.42 to 1.08; p=0.10). The recovery rate for the two groups was similar during the 5-day intervention, but for 2 days after the end of zinc/placebo use, the zinc participants recovered significantly slower compared with the placebo participants (p=0.003). In the zinc group, 37% did not report adverse effects, the corresponding proportion being 69% in the placebo group., Conclusions: A commercially available zinc acetate lozenge was not effective in treating the common cold when instructed to be used for 5 days after the first symptoms. Taste has been a common problem in previous zinc lozenge trials, but a third of zinc participants did not complain of any adverse effects. More research is needed to evaluate the characteristics of zinc lozenges that may be clinically efficacious before zinc lozenges can be widely promoted for common cold treatment., Trial Registration Number: NCT03309995., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

A 37-year-old Wilson disease patient treated with D-penicillamine visited our hospital for the evaluation of his liver function. Laboratory data showed a low serum copper level and ceruloplasmin. The ratio of urinary copper to urinary creatinine in a spot urinary analysis after 4 days' cessation of D-penicillamine was under 0.1. We concluded that the copper chelation was excessive and changed D-penicillamine to zinc acetate. However, his liver function test results did not normalize. We performed a liver biopsy and discovered a high copper content. The liver dysfunction was improved after resuming chelating therapy. Accurate measurement of the hepatic copper content via a biopsy is important for the adequate management of this disease.

Background:Environmental copper has been implicated in the pathogenesis of Alzheimer’s disease based on evidence that: 1) brain copper levels increase with age, 2) copper promotes misfolding and toxicity of amyloid-β in vitro, 3) copper-modulating interventions reduce amyloid pathology in animal models. However, the effect of copper upon non-amyloid Alzheimer’s pathology is relatively under-explored.Objective:To determine if modulation of brain copper level affects brain tau pathology and/or associated cognitive impairment.Methods:We tested the hypothesis that brain copper modulates tau pathology by manipulating brain levels of copper in the PS19 transgenic mouse model of tau pathology. We treated PS19 and wild-type mice with oral zinc acetate, an established therapy for long term control of excess brain copper, and examined treatment effects upon brain copper, brain tau, NFT-like pathology, and spatial memory. We treated a second cohort of mice with exogenous dietary copper in order to evaluate whether excess environmental copper promotes brain tau pathology.Results:Copper-lowering with oral zinc attenuated spatial memory impairment in female but not male PS19 mice, without a significant effect upon tau pathology. Copper loading increased brain copper, but did not have an effect on brain tau pathology or spatial memory function.Conclusion:These findings suggest that a strategy to lower brain copper may be viable for symptomatic benefit in the setting of tau neuropathology, but unlikely to have robust effects on the underlying pathology. These findings are consistent with dietary or other exogenous copper being unlikely to promote tau pathology.

Zinc is one of the most important essential trace elements. It is involved in more than 300 enzyme systems and is an indispensable participant in many biochemical processes. Zinc deficiency causes a number of disorders in the human body, the main ones being the delay of growth and puberty, immune disorders, and cognitive dysfunctions. There are over two billion people in the world suffering from zinc deficiency conditions. Acyzol, a zinc-containing medicine, developed as an antidote against carbon monoxide poisoning, demonstrates a wide range of pharmacological activities: Anti-inflammatory, reparative, detoxifying, immunomodulatory, bacteriostatic, hepatoprotective, adaptogenic, antioxidant, antihypoxic, and cardioprotective. The presence of zinc in the composition of Acyzol suggests the potential of the drug in the treatment and prevention of zinc deficiency conditions, such as Prasad's disease, immune system pathology, alopecia, allergodermatoses, prostate dysfunction, psoriasis, stomatitis, periodontitis, and delayed mental and physical development in children. Currently, the efficiency of Acyzol in the cases of zinc deficiency is shown in a large number of experimental studies. So, Acyzol can be used as a highly effective drug for pharmacologic therapy of a wide range of diseases and conditions and it opens up new perspectives in the treatment and prevention of zinc deficiency conditions.

Immunoglobulin A nephropathy is the most common primary glomerulonephritis worldwide, and it can be associated with liver disease. However, cases of Immunoglobulin A nephropathy secondary to Wilson's disease are very rare. A 20-year-old Japanese man presented with microscopic hematuria, proteinuria, and renal dysfunction. A renal biopsy showed mesangial cell proliferation, immunoglobulin A deposition, and electron-dense deposit in the mesangial areas, all of which are consistent with Immunoglobulin A nephropathy. Computed tomography of the abdomen showed liver atrophy and splenomegaly, and the diagnosis of Wilson's disease was confirmed with decreased serum ceruloplasmin levels, increased urinary copper excretion, Kayser-Fleischer rings and copper deposition in the liver biopsy. The patient was treated successfully with trientine hydrochloride and zinc acetate and showed improvement in renal manifestations. Wilson's disease is a rare cause of secondary Immunoglobulin A nephropathy. We recommend that Wilson's disease should be considered the cause of secondary Immunoglobulin A nephropathy in juvenile patients with hematuria, proteinuria, and splenomegaly and suggest measuring the serum ceruloplasmin concentrations, urinary copper excretion, and evaluating Kayser-Fleischer rings in these patients.

A 64-year-old woman was referred to our hospital with jaundice of the bulbar conjunctiva and general fatigue. After admission, she developed hepatic encephalopathy and was diagnosed with fulminant hepatitis based on the American Association for the Study of Liver Disease (AASLD) position paper. Afterwards, additional laboratory findings revealed that serum ceruloplasmin levels were reduced, urinary copper levels were greatly elevated and Wilson's disease (WD)-specific routine tests were positive, but the Kayser-Fleischer ring was not clear. Based on the AASLD practice guidelines for the diagnosis and treatment of WD, the patient was ultimately diagnosed with fulminant WD. Then, administration of penicillamine and zinc acetate was initiated; however, the patient unfortunately died from acute pneumonia on the 28 th day of hospitalization. At autopsy, the liver did not show a bridging pattern of fibrosis suggestive of chronic liver injury. Here, we present the case of a patient with clinically diagnosed late-onset fulminant WD without cirrhosis, who had positive disease-specific routine tests., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare.

Aim: To evaluate the long-term effects of a zinc acetate and chlorhexidine diacetate mouth rinse (Zn/CHX) on intra-oral halitosis., Materials and Methods: Forty-six adults with intra-oral halitosis were randomized into a 6-month, double-blind, placebo-controlled clinical study. The presence of intra-oral halitosis was evaluated at baseline, 3 and 6 months after treatment by assessment of organoleptic score (OLS) and by total volatile sulphur compounds (T-VSC), hydrogen sulphide (H 2 S) and methyl mercaptan (MM) concentrations in exhaled air., Results: A Zn/CHX mouth rinse provided significantly better control of intra-oral halitosis than a placebo mouth rinse. At 3 and 6 months, individuals rinsing with the Zn/CHX rinse presented with reductions of the OLS, T-VSC (p < .01, respectively), H 2 S (p < .001), and MM (p < .01) in subjects' exhaled air. At 6 months, 68.2% of individuals using the Zn/CHX rinse experienced a 1 or 2 category improvement in OLS compared with 19.1% of placebo-treated subjects. 91% of subjects in the Zn/CHX group were categorized as being effectively treated for intra-oral halitosis (i.e. H 2 S < 112 ppb), compared to 43% in the placebo group., Conclusion: Zn/CHX mouth rinse provides effective long-term efficacy against intra-oral halitosis, assessed both objectively and subjectively. With regular rinsing, the effect was sustained for 6 months., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aims: The aim of this study was to determine whether the allergy status and other characteristics of common cold patients modify the effects of zinc acetate lozenges., Methods: We had available individual patient data for three randomized placebo-controlled trials in which zinc acetate lozenges were administered to common cold patients. We used both one stage and two stage meta-analysis to estimate the effects of zinc lozenges., Results: The total number of common cold patients was 199, the majority being females. Eighty percent of them fell into the age range 20-50 years. One third of the patients had allergies. The one stage meta-analysis gave an overall estimate of 2.73 days (95% CI 1.8, 3.3 days) shorter colds by zinc acetate lozenge usage. The two stage meta-analysis gave an estimate of 2.94 days (95% CI 2.1, 3.8 days) reduction in common cold duration. These estimates are to be compared with the 7 day average duration of colds in the three trials. The effect of zinc lozenges was not modified by allergy status, smoking, baseline severity of the common cold, age, gender or ethnic group., Conclusion: Since the effects of zinc acetate lozenges were consistent between the compared subgroups, the overall estimates for effect seemed applicable over a wide range of common cold patients. While the optimal composition of zinc lozenges and the best frequency of their administration should be further investigated, given the current evidence of efficacy, common cold patients may be encouraged to try zinc lozenges for treating their colds., (© 2016 The British Pharmacological Society.)

Aim: To evaluate the effect of different mouth rinses 12 h after rinsing on genuine intra-oral halitosis., Materials and Methods: Twenty-four adults with halitosis were included in a double-blind, crossover, randomized clinical trial. Halitosis was evaluated 12 h after rinsing with placebo and five mouth rinse products containing zinc acetate and chlorhexidine diacetate; zinc lactate, chlorhexidine and cetylpyridinium chloride; zinc acetate and chlorhexidine diacetate with reduced amounts of mint and menthol; zinc chloride and essential oil; and chlorine dioxide using the organoleptic method and a gas chromatograph. Test periods were separated by 1 week., Results: Hydrogen sulphide (H2 S), methyl mercaptan (MM) and the organoleptic scores (OLS) were significantly reduced 12 h following rinsing with all substances compared to placebo (P < 0.05). H2 S was more effectively reduced after rinsing with zinc acetate and chlorhexidine diacetate and zinc acetate and chlorhexidine diacetate with reduced amounts of mint and menthol compared to rinsing with zinc chloride and essential oil (P < 0.05), and significantly lower values of MM were obtained after rinsing with zinc acetate and chlorhexidine diacetate compared to zinc lactate, chlorhexidine and cetylpyridinium chloride (P < 0.05). The percentage effectively treated individuals (H2 S (<112 ppb), MM (<26 ppb) and OLS score <2) varied from 58% percentage (zinc acetate and chlorhexidine diacetate) to 26% (zinc chloride and essential oil)., Conclusion: All treatments resulted in reduction in halitosis 12 h after rinsing compared to placebo. H2 S and MM were most effectively reduced by zinc acetate and chlorhexidine diacetate., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background and Aims: Zinc therapy is considered a good option in Wilson disease (WD), as a first-line treatment in presymptomatic children and a maintenance therapy after the initial chelator therapy. The aim of the study was to determine the practical use of zinc treatment in French pediatric centers., Methods: A national survey was conducted in the 6 French centers using zinc acetate to treat WD. Clinical and biological parameters, dosage, and outcome were recorded., Results: A total of 26 children were reported to be treated with zinc acetate, alone or in association with chelators. Of the 9 children (35%) who received zinc alone as a first-line therapy, 2 were switched to D-penicillamine because of inefficacy and 7 remained on zinc alone, but serum transaminase levels normalized in only 4 of them. Five children (19%) were initially treated with zinc in association with D-penicillamine (n = 4) or Trientine (n = 1) with good efficacy. Among the 12 children (46%) who received zinc as a maintenance therapy after D-penicillamine, no relapse of hepatic cytolysis occurred during a median follow-up of 5.2 years, but 2 of them were switched to Trientine because of zinc-related adverse effects. Epigastric pain was observed in 4 children, and a gastric perforation occurred in 1 child., Conclusions: The present study demonstrates poor efficacy of zinc as first-line therapy to control liver disease in half presymptomatic children and a high incidence of related gastrointestinal adverse effects in children with WD.

The transmission of both cell-free and cell-associated immunodeficiency viruses has been demonstrated directly in multiple animal species and possibly occurs in humans, as suggested by genotyping of the infecting human immunodeficiency virus (HIV) in acutely infected women and in semen from their partners. Therefore, a microbicide may need to block both mechanisms of HIV transmission to achieve maximum efficacy. To date, most of the preclinical evaluation of candidate microbicides has been performed using cell-free HIV. New models of mucosal transmission of cell-associated HIV are needed to evaluate candidate microbicide performance. The MIV-150/zinc acetate/carrageenan (MZC) gel protects Depo-Provera-treated macaques against cell-free simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) infection when applied vaginally up to 8 h before challenge. We recently demonstrated the potent activity of MZC gel against cell-free SHIV-RT in macaque vaginal explants. In the current study, we established a cell-associated SHIV-RT infection model of macaque vaginal tissues and tested the activity of MZC gel in this model. MZC gel protected tissues against cell-associated SHIV-RT infection when present at the time of viral exposure or when applied up to 4 days prior to viral challenge. These data support clinical testing of the MZC gel. Overall, our ex vivo model of cell-associated SHIV-RT infection in macaque vaginal mucosa complements the cell-free infection models, providing tools for prioritization of products that block both modes of HIV transmission., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

A 37-year-old male patient presented with psychiatric symptoms, dysarthria, limb dystonia, increased tendon reflexes, and a Kayser-Fleischer ring in his late teens. Laboratory examinations showed decreased concentrations of serum copper and ceruloplasmin, and increased urinary copper levels. Magnetic resonance imaging (MRI) showed high-signal-intensity lesions in the bilateral putamen, globus pallidus, thalamus, and brainstem on T2-weighted images (T2WI). Based on the MRI results and laboratory data, we diagnosed this patient with Wilson's disease (WD). He was treated with trientine hydrochloride and zinc acetate. Four months after the initiation of treatment, the patient'symptoms began to improve. On a follow-up MRI that was obtained 6 years after treatment, the high-signal-intensity lesions on the T2WI had disappeared completely. However, the low-signal-intensity lesions in the basal ganglia had spread to the caudate nuclei. Here, we discuss the characteristics of the MRI changes in WD following treatment. The Pathological basis for the low-signal-intensity lesions on T2WI in WD remains unclear. Our results suggest that this lesion may reflect the accumulation of materials other than copper.

Objective: To our knowledge, no randomized study has shown whether zinc replacement therapy is effective for hyperammonemia in liver cirrhosis; therefore, we performed a double-blind, placebo-controlled trial to examine efficacy and safety of the zinc replacement therapy., Methods: Patients with liver cirrhosis and hyperammonemia (at or above the institutional reference value) and hypozincemia (≤65 μg/dL) were enrolled in the outpatient units of the participating institutions and were randomly divided to receive placebo (P group) or zinc acetate preparation at a dose of 3 capsules/d for a total zinc content of 150 mg/d (Z group) by the envelope method. Of the 18 enrolled patients, 6 dropped out; thus, the analyses included 12 patients (5 in the P group and 7 in the Z group). Variations in blood concentrations of zinc and ammonia as well as liver function test results were compared., Results: Blood zinc levels significantly increased in the Z group (P = 0.0037; Friedman test) but not the P group. Blood ammonia levels significantly decreased in the Z group (P = 0.0114; Friedman test) but not the P group. The percent change in blood ammonia level also revealed significant reduction at the eighth week in the Z group (P = 0.0188: Mann-Whitney test). No serious adverse events attributable to the zinc preparation were noted., Conclusion: Although this study is preliminary and includes a small sample, it is, to our knowledge, the first randomized controlled trial to show that zinc supplementation for 3 mo seems effective and safe for treating hyperammonemia in liver cirrhosis. Studies with a larger sample size are needed to confirm our findings., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Otitis media is inflammation of the middle ear and is usually caused by infection. It affects people of all ages but is particularly common in young children. Around 164 million people worldwide have long-term hearing loss caused by this condition, 90% of them in low-income countries. As zinc supplements prevent pneumonia in disadvantaged children, we wanted to investigate whether zinc supplements could also prevent otitis media., Objectives: To evaluate whether zinc supplements prevent otitis media in adults and children of different ages., Search Methods: We searched CENTRAL (2014, Issue 1), MEDLINE (1950 to February week 4, 2014) and EMBASE (1974 to March 2014)., Selection Criteria: Randomised, placebo-controlled trials of zinc supplements given at least once a week for at least a month for preventing otitis media., Data Collection and Analysis: Two review authors independently assessed the eligibility and methodological quality of the included trials and extracted and analysed data. We summarised results using risk ratios (RRs) or rate ratios for dichotomous data and mean differences (MDs) for continuous data. We combined trial results where appropriate., Main Results: No new trials were identified for inclusion in this update. We identified 12 trials for inclusion, 10 of which contributed outcomes data. There were a total of 6820 participants. In trials of healthy children living in low-income communities, two trials did not demonstrate a significant difference between the zinc-supplemented and placebo groups in the numbers of participants experiencing an episode of definite otitis media during follow-up (3191 participants); another trial showed a significantly lower incidence rate of otitis media in the zinc group (rate ratio 0.69, 95% confidence interval (CI) 0.61 to 0.79, n = 1621). A small trial of 39 infants undergoing treatment for severe malnutrition suggested a benefit of zinc for the mean number of episodes of otitis media (mean difference (MD) -1.12 episodes, 95% CI -2.21 to -0.03). Zinc supplements did not seem to cause any serious adverse events but a small minority of children were reported to have vomited shortly after ingestion of the supplements. The trial evidence included is generally of good quality, with a low risk of bias., Authors' Conclusions: Evidence on whether zinc supplementation can reduce the incidence of otitis media in healthy children under the age of five years living in low- and middle-income countries is mixed. There is some evidence of benefit in children being treated for marasmus (severe malnutrition), but this is based on one small trial and should therefore be treated with caution.

MEDNIK (mental retardation, enteropathy, deafness, neuropathy, ichthyosis, and keratodermia) syndrome has been recently described as a new disorder of copper metabolism. This multisystem disease combines clinical and biochemical signs of both Menkes and Wilson's diseases, in which liver copper overload is treatable using zinc acetate therapy. MEDNIK syndrome is caused by mutation of the AP1S1 gene, which codes for the σ1A subunit of adaptor protein complex 1, and directs intracellular trafficking of copper pumps ATP7A and ATP7B. Adaptor protein complexes regulate clathrin-coated vesicle assembly, protein cargo sorting, and vesicular trafficking between organelles in eukaryotic cells. A growing number of diseases have been associated with mutations in genes coding for adaptor protein complexes subunits and we propose for them the term adaptinopathies, as a new organic category of disorders of intracellular trafficking, which offers the opportunity to dissect the mechanisms involved in the crosstalk between the Golgi apparatus and the other organelles., (© 2014 New York Academy of Sciences.)

Background: The common cold is one of the most widespread illnesses and is a leading cause of visits to the doctor and absenteeism from school and work. Trials conducted in high-income countries since 1984 investigating the role of zinc for the common cold symptoms have had mixed results. Inadequate treatment masking and reduced bioavailability of zinc from some formulations have been cited as influencing results., Objectives: To assess whether zinc (irrespective of the zinc salt or formulation used) is efficacious in reducing the incidence, severity and duration of common cold symptoms. In addition, we aimed to identify potential sources of heterogeneity in results obtained and to assess their clinical significance., Search Methods: In this updated review, we searched CENTRAL (2012, Issue 12), MEDLINE (1966 to January week 2, 2013), EMBASE (1974 to January 2013), CINAHL (1981 to January 2013), Web of Science (1985 to January 2013), LILACS (1982 to January 2013), WHO ICTRP and clinicaltrials.gov., Selection Criteria: Randomised, double-blind, placebo-controlled trials using zinc for at least five consecutive days to treat, or for at least five months to prevent the common cold., Data Collection and Analysis: Two review authors independently extracted data and assessed trial quality., Main Results: Five trials were identified in the updated searches in January 2013 and two of them did not meet our inclusion criteria. We included 16 therapeutic trials (1387 participants) and two preventive trials (394 participants). Intake of zinc was associated with a significant reduction in the duration (days) (mean difference (MD) -1.03, 95% confidence interval (CI) -1.72 to -0.34) (P = 0.003) (I(2) statistic = 89%) but not the severity of common cold symptoms (MD -1.06, 95% CI -2.36 to 0.23) (P = 0.11) (I(2) statistic = 84%). The proportion of participants who were symptomatic after seven days of treatment was significantly smaller (odds ratio (OR) 0.45, 95% CI 0.20 to 1.00) (P = 0.05) than those in the control, (I(2 )statistic = 75%). The incidence rate ratio (IRR) of developing a cold (IRR 0.64, 95% CI 0.47 to 0.88) (P = 0.006) (I(2) statistic = 88%), school absence (P = 0.0003) and prescription of antibiotics (P < 0.00001) was lower in the zinc group. Overall adverse events (OR 1.58, 95% CI 1.19 to 2.09) (P = 0.002), bad taste (OR 2.31, 95% CI 1.71 to 3.11) (P < 0.00001) and nausea (OR 2.15, 95% CI 1.44 to 3.23) (P = 0.002) were higher in the zinc group. The very high heterogeneity means that the averaged estimates must be viewed with caution., Authors' Conclusions: Zinc administered within 24 hours of onset of symptoms reduces the duration of common cold symptoms in healthy people but some caution is needed due to the heterogeneity of the data. As the zinc lozenges formulation has been widely studied and there is a significant reduction in the duration of cold at a dose of ≥ 75 mg/day, for those considering using zinc it would be best to use it at this dose throughout the cold. Regarding prophylactic zinc supplementation, currently no firm recommendation can be made because of insufficient data. When using zinc lozenges (not as syrup or tablets) the likely benefit has to be balanced against side effects, notably a bad taste and nausea.

MEDNIK syndrome-acronym for mental retardation, enteropathy, deafness, neuropathy, ichthyosis, keratodermia-is caused by AP1S1 gene mutations, encoding σ1A, the small subunit of the adaptor protein 1 complex, which plays a crucial role in clathrin coat assembly and mediates trafficking between trans-Golgi network, endosomes and the plasma membrane. MEDNIK syndrome was first reported in a few French-Canadian families sharing common ancestors, presenting a complex neurocutaneous phenotype, but its pathogenesis is not completely understood. A Sephardic-Jewish patient, carrying a new AP1S1 homozygous mutation, showed severe perturbations of copper metabolism with hypocupremia, hypoceruloplasminemia and liver copper accumulation, along with intrahepatic cholestasis. Zinc acetate treatment strikingly improved clinical conditions, as well as liver copper and bile-acid overload. We evaluated copper-related metabolites and liver function retrospectively in the original French-Canadian patient series. Intracellular copper metabolism and subcellular localization and function of copper pump ATP7A were investigated in patient fibroblasts. Copper metabolism perturbation and hepatopathy were confirmed in all patients. Studies in mutant fibroblasts showed abnormal copper incorporation and retention, reduced expression of copper-dependent enzymes cytochrome-c-oxidase and Cu/Zn superoxide dismutase, and aberrant intracellular trafficking of Menkes protein ATP7A, which normalized after rescue experiments expressing wild-type AP1S1 gene. We solved the pathogenetic mechanism of MEDNIK syndrome, demonstrating that AP1S1 regulates intracellular copper machinery mediated by copper-pump proteins. This multisystem disease is characterized by a unique picture, combining clinical and biochemical signs of both Menkes and Wilson's diseases, in which liver copper overload is treatable by zinc acetate therapy, and can now be listed as a copper metabolism defect in humans. Our results may also contribute to understand the mechanism(s) of intracellular trafficking of copper pumps.

Objectives: This study aims to assess the effects of rinsing with zinc- and chlorhexidine-containing mouth rinse with or without adjunct tongue scraping on volatile sulfur compounds (VSCs) in breath air, and the microbiota at the dorsum of the tongue., Material and Methods: A randomized single-masked controlled clinical trial with a cross-over study design over 14 days including 21 subjects was performed. Bacterial samples from the dorsum of the tongue were assayed by checkerboard DNA-DNA hybridization., Results: No halitosis (identified by VSC assessments) at day 14 was identified in 12/21 subjects with active rinse alone, in 10/21 with adjunct use of tongue scraper, in 1/21 for negative control rinse alone, and in 3/21 in the control and tongue scraping sequence. At day 14, significantly lower counts were identified only in the active rinse sequence (p < 0.001) for 15/78 species including, Fusobacterium sp., Porphyromonas gingivalis, Pseudomonas aeruginosa, Staphylococcus aureus, and Tannerella forsythia. A decrease in bacteria from baseline to day 14 was found in successfully treated subjects for 9/74 species including: P. gingivalis, Prevotella melaninogenica, S. aureus, and Treponema denticola. Baseline VSC scores were correlated with several bacterial species. The use of a tongue scraper combined with active rinse did not change the levels of VSC compared to rinsing alone., Conclusions: VSC scores were not associated with bacterial counts in samples taken from the dorsum of the tongue. The active rinse alone containing zinc and chlorhexidine had effects on intra-oral halitosis and reduced bacterial counts of species associated with malodor. Tongue scraping provided no beneficial effects on the microbiota studied., Clinical Relevance: Periodontally healthy subjects with intra-oral halitosis benefit from daily rinsing with zinc- and chlorhexidine-containing mouth rinse.

As Wilson's disease is both preventable and treatable, the diagnosis must not be missed. Despite this, it is usually misdiagnosed. Misdiagnosis and delay in treatment are clinically relevant because if left untreated, Wilson's disease progresses to hepatic failure or severe neurologic disability, and death. Those adequately treated have a normal life span. Wilson's disease is an autosomal recessive disease caused by mutations in the ATP7B gene. Mutations in ATP7B result in abnormal copper metabolism and subsequent toxic accumulation of copper. The clinical manifestations of neurologic Wilson's disease include variable combinations of dysarthria, dystonia, tremor, parkinsonism, ataxia, and choreoathetosis. Once the possibility of Wilson's disease is considered, diagnosis is straight forward. Currently available treatments, including zinc acetate and trientine, are generally well tolerated and effective., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Wilson's disease is a rare genetic disorder of copper metabolism. The difference in copper tissue accumulation is responsible for the various clinical manifestations of this disorder. If left untreated, Wilson's disease progresses to hepatic failure, severe neurological disability, and even death. Due to the complex clinical picture of Wilson's disease, its diagnosis relies on a high index of suspicion. In our paper, we present endocrine symptoms suggesting the presence of insulinoma and hyperprolactinemia as the initial clinical manifestation of Wilson's disease in a young female. Zinc acetate treatment resulted in the disappearance of hypoglycemia, galactorrhea, and menstrual abnormalities.

Objectives: To assess the effects on intra-oral halitosis by a mouth rinse containing zinc acetate (0.3%) and chlorhexidine diacetate (0.025%) with and without adjunct tongue scraping., Materials and Methods: Twenty-one subjects without a diagnosis of periodontitis were randomized in a cross-over clinical trial. Organoleptic scores (OLS) were assessed to define intra-oral halitosis by total volatile sulfur compound (T-VSC) measurements and by gas chromatography., Results: Twenty-one subjects with a mean age of 45.7 years (SD: ±13.3, range: 21-66). The OLS were significantly lower following active rinse combined with tongue scraping (p < 0.001) at all time points. Immediately after, at 30 min, and at day 14, the T-VSC values were lower in the active rinse sequence than in the negative rinse sequence (p < 0.001, p < 0.001 and p < 0.05, respectively). At 30 min and at day 14, the hydrogen sulfide (H(2)S) and methyl mercaptan (MM) values were lower in the active rinse sequence compared to the inactive rinse sequence (p < 0.001). The inactive rinse sequence with tongue scraping reduced T-VSC at 30 min (p < 0.001) but not at 14 days. Similar reductions in T-VSC, H(2)S and MM were found in the active rinse sequence with or without tongue scraping., Conclusion: The use of a tongue scraper did not provide additional benefits to the active mouth rinse, but reduced OLS and tongue coating index.

Background: Otitis media (OM) is inflammation of the middle ear and is usually caused by infection. It affects people of all ages but is particularly common in young children. Around 164 million people worldwide have long-term hearing loss caused by this condition, 90% of them in low-income countries. As zinc supplements prevent pneumonia in disadvantaged children, we wanted to investigate whether zinc supplements could also prevent OM., Objectives: To evaluate whether zinc supplements prevent OM in adults and children of different ages., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2012, Issue 1) which includes the Cochrane Acute Respiratory Infections Groups' Specialised Register, MEDLINE (1950 to February week 1, 2012) and EMBASE (1974 to February 2012)., Selection Criteria: Randomised, placebo-controlled trials of zinc supplements given at least once a week for at least a month for preventing OM., Data Collection and Analysis: Two review authors independently assessed the eligibility and methodological quality of the included trials and extracted and analysed data. We summarised results using risk ratios (RRs) or rate ratios for dichotomous data and mean differences (MDs) for continuous data. We combined trial results where appropriate., Main Results: We identified 12 trials for inclusion, 10 of which contributed outcomes data. There was a total of 6820 participants. In trials of healthy children living in low-income communities, two trials did not demonstrate a significant difference between the zinc supplemented and placebo groups in the numbers of participants experiencing an episode of definite OM during follow-up (3191 participants); another trial showed a significantly lower incidence rate of OM in the zinc group (rate ratio 0.69, 95% confidence interval (CI) 0.61 to 0.79, n = 1621). A small trial of 39 infants undergoing treatment for severe malnutrition suggested a benefit of zinc for the mean number of episodes of OM (mean difference (MD) -1.12 episodes, 95% CI -2.21 to -0.03). Zinc supplements did not seem to cause any serious adverse events but a small minority of children were reported to have vomited shortly after ingestion of the supplements. The trial evidence included is generally of good quality, with a low risk of bias., Authors' Conclusions: Evidence on whether zinc supplementation can reduce the incidence of OM in healthy children under the age of five years living in low- and middle-income countries is mixed. There is some evidence of benefit in children being treated for marasmus (severe malnutrition) but this is based on one small trial and should therefore be treated with caution.

We describe a 17-year-old girl with haemolytic anaemia as presentation of Wilson disease. The diagnosis was based on the findings of < 20 mg/dl ceruloplasmin serum level, Kayser-Fleischer ring and Coombs-negative haemolytic anaemia. Genetic testing revealed the presence of the H1069Q heterozygous mutation. The patient was treated with Zinc acetate monotherapy, with good response, maintened after 22 months. This case emphasizes the importance of recognizing atypical clinical presentation of Wilson disease, which must always be considered in patients with Coombs-negative haemolytic anaemia. The good clinical response to treatment with zinc acetate monotherapy in our case might lend to consider the use of zinc monotherapy as initial therapy also in symptomatic patients with Wilson disease under close clinical observation. Clinical trials are needed to provide evidence for use of zinc monotherapy as first-line therapy in symptomatic patients with Wilson disease.

Oral submucous fibrosis is a chronic debilitating disorder which is usually seen in adults with areca nut chewing habit. A rapid upsurge in the popularity of commercial areca nut products, especially among the younger generation, is a cause of grave concern, as satisfactory management is still lacking. Hereby, two pediatric cases of oral submucous fibrosis are reported.

Objective: A controlled, clinical, double-blind study was conducted to assess the efficacy of a sugar-free chewing gum containing zinc acetate and magnolia bark extract (MBE) on oral volatile sulfur-containing compounds (VSC) versus a placebo sugar-free chewing gum for two hours., Methods: To participate in the study, subjects had to have at least 24 of their teeth, no report of oral and systemic diseases, and no removable dentures. All 168 eligible participants had to avoid any professional oral hygiene, refrain from taking medicine for two weeks, and not be menstruating. They were also instructed not to brush their teeth and tongue, smoke, drink alcohol, or eat onion, garlic, or licorice for the six-hour period before the visit and during the test. Moreover, to join the protocol, they had to show a VSC score of > or = 75 ppb at the baseline measurement. One-hundred and twenty-three subjects (67 men and 56 women, mean age 37) met the criteria at baseline and were entered into either the test or control group by assignment from a table of randomized numbers. The test chewing gum (2.23 g) contained zinc acetate 0.012% and magnolia bark extract 0.15% in weight; the control gum was equivalent without these active agents. The OralChroma device was utilized to evaluate total oral VSC. Their levels were recorded at baseline, after ten minutes of mastication, after one hour, and after two hours. Data were analyzed with SPSS software and the level of significance was set at alpha = 0.05., Results: One-hundred and twenty-three subjects completed the trial (62 in the control group and 61 in the test group); none reported problems linked to zinc acetate or magnolia bark extract. The mean percentage reductions from baseline at the end of the 10-minute chewing were 31.2% in the control group (p < 0.05) and 50.9% in the test group (p < 0.05). One hour later the reductions were 6.9% in the control group and 27.6% in the test group (p < 0.05); two hours later the reductions were 2.3% in the control group and 13.6% in the test group. The comparison of the two groups after baseline adjustment showed a statistically significant difference (p < 0.05) in VSC reductions between the test and control chewing gums at the end of the mastication period and after one hour., Conclusion: Chewing gum containing zinc acetate and magnoliabark extract can significantly reduce the oral VSC levels for more than one hour. Moreover, the test chewing gum reduces oral VSC significantly more than a control chewing gum.

A 38-year-old woman with Wilson's disease developed neurological deterioration after 25 years of low-dose penicillamine administration. She showed an akinetic-rigid syndrome and cerebellar motor ataxia. Brain MRI showed increased signal intensity at the bilateral pons, midbrain, putamen, and thalamus. 123I-IMP-SPECT revealed a diffuse reduction of cerebral blood flow at the bilateral cerebral hemisphere including the basal ganglia. After the patient's regimen was changed to zinc therapy, her neurological condition gradually improved, and she showed almost complete recovery within two years. Serial MRI and SPECT studies showed a marked improvement in the lesions.

Topical microbicides that block the sexual transmission of HIV and herpes simplex virus 2 (HSV-2) are desperately needed to reduce the incidence of HIV infections worldwide. Previously we completed phase 3 testing of the carrageenan-based gel Carraguard. Although the trial did not show that Carraguard is effective in preventing HIV transmission during vaginal sex, it did show that Carraguard is safe when used weekly for up to 2 years. Moreover, Carraguard has in vitro activity against human papillomavirus (HPV) and HSV-2 and favorable physical and rheological properties, which makes it a useful vehicle to deliver antiviral agents such as zinc acetate. To that end, we previously reported that a prototype zinc acetate carrageenan gel protects macaques against vaginal challenge with combined simian-human immunodeficiency virus reverse transcriptase (SHIV-RT). Herein, we report the safety and efficacy of a series of zinc acetate and/or carrageenan gels. The gels protected mice (75 to 85% survival; P < 0.001) against high-dose (10(6)-PFU) HSV-2 vaginal or rectal challenge. In contrast, zinc acetate formulated in HEC (hydroxyethylcellulose; or the Universal Placebo) failed to protect mice against the high-dose vaginal HSV-2 challenge (similar to aqueous zinc acetate solution and the placebo controls). The gels were found to be effective spreading gels, exhibited limited toxicity in vitro, caused minimal damage to the architecture of the cervicovaginal and rectal mucosae in vivo, and induced no increased susceptibility to HSV-2 infection in a mouse model. Our results provide a strong rationale to further optimize and evaluate the zinc acetate/carrageenan gels for their ability to block the sexual transmission of HIV and HSV-2.

Aim: To evaluate whether combination therapy with anti-tumour necrosis factor α (TNFα) antibody and Zn acetate is beneficial in dextran sodium sulphate (DSS) colitis., Methods: Colitis was induced in CD1-Swiss mice with 5% DSS for 7 d. The experimental mice were then randomised into the following subgroups: standard diet + DSS treated (induced colitis group); standard diet + DSS + subcutaneous 25 μg anti-TNFα treated group; Zn acetate treated group + DSS + subcutaneous 25 μg anti-TNFα; standard diet + DSS + subcutaneous 6.25 μg anti-TNFα treated group and Zn acetate treated group + DSS + subcutaneous 6.25 μg anti-TNFα. Each group of mice was matched with a similar group of sham control animals. Macroscopic and histological features were scored blindly. Homogenates of the colonic mucosa were assessed for myeloperoxidase activity as a biochemical marker of inflammation and DNA adducts (8OH-dG) as a measure of oxidative damage., Results: DSS produced submucosal erosions, ulcers, inflammatory cell infiltration and cryptic abscesses which were reduced in both groups of mice receiving either anti-TNFα alone or combined with zinc. The effect was more pronounced in the latter group (vs Zn diet, P < 0.02). Myeloperoxidase activity (vs controls, P < 0.02) and DNA adducts, greatly elevated in the DSS fed colitis group (vs controls, P < 0.05), were significantly reduced in the treated groups, with a more remarkable effect in the group receiving combined therapy (vs standard diet, P < 0.04)., Conclusion: DSS induces colonic inflammation which is modulated by the administration of anti-TNFα. Combining anti-TNFα with Zn acetate offers marginal benefit in colitis severity.

Background: Repeated use, coitus-independent microbicide gels that do not contain antiretroviral agents also used as first line HIV therapy are urgently needed to curb HIV spread. Current formulations require high doses (millimolar range) of antiretroviral drugs and typically only provide short-term protection in macaques. We used the macaque model to test the efficacy of a novel combination microbicide gel containing zinc acetate and micromolar doses of the novel non-nucleoside reverse transcriptase inhibitor MIV-150 for up to 24 h after repeated gel application., Methods and Findings: Rhesus macaques were vaginally challenged with SHIV-RT up to 24 h after repeated administration of microbicide versus placebo gels. Infection status was determined by measuring virologic and immunologic parameters. Combination microbicide gels containing 14 mM zinc acetate dihydrate and 50 µM MIV-150 afforded full protection (21 of 21 animals) for up to 24 h after 2 weeks of daily application. Partial protection was achieved with the MIV-150 gel (56% of control at 8 h after last application, 11% at 24 h), while the zinc acetate gel afforded more pronounced protection (67% at 8-24 h). Marked protection persisted when the zinc acetate or MIV-150/zinc acetate gels were applied every other day for 4 weeks prior to challenge 24 h after the last gel was administered (11 of 14 protected). More MIV-150 was associated with cervical tissue 8 h after daily dosing of MIV-150/zinc acetate versus MIV-150, while comparable MIV-150 levels were associated with vaginal tissues and at 24 h., Conclusions: A combination MIV-150/zinc acetate gel and a zinc acetate gel provide significant protection against SHIV-RT infection for up to 24 h. This represents a novel advancement, identifying microbicides that do not contain anti-viral agents used to treat HIV infection and which can be used repeatedly and independently of coitus, and underscores the need for future clinical testing of their safety and ability to prevent HIV transmission in humans.

Background and Aims: Wilson disease (WD) is an inherited disorder of copper metabolism. When treated, the outcome can be excellent, although the long-term survival has yet to be well documented. The aim of this study was to describe the long-term outcome of a cohort of patients with WD and to assess those factors affecting the phenotypic manifestation of WD., Methods: The presence of mutations to the ATP7B gene, the clinical manifestations, treatments and the long-term outcomes were analysed retrospectively in 117 patients with WD (59 men and 58 women, aged at evaluation 38.5 ± 11, range 16-63 years)., Results: Fifty-five patients with a neurological presentation, 51 patients with a hepatic presentation and 11 asymptomatic patients were followed up for an average of 15.1 ± 10 years (median 12 years, range 1-41 years). The H1069Q ATP7B gene mutation was the most frequent genetic variant (54.3%); the frequency of this mutation did not differ between patients with either the hepatic or the neurological presentation (P = 0.099). d-penicillamine or zinc salts (81 and 17% respectively) were used for treatment, and three patients underwent liver transplantation. The majority of symptomatic patients became asymptomatic, or improved, during the follow-up (82% patients with hepatic presentation, 69% with neurological presentation). The long-term survival of patients with WD did not differ from that of the general Czech population (P = 0.95)., Conclusions: Long-term follow-up shows a satisfactory response in the great majority of adequately treated patients with WD and survival coincides with that of the general population., (© 2010 John Wiley & Sons A/S.)

Wilson disease is an autosomal recessive disorder with copper metabolism. In Japan, the standard treatment is the administration of copper chelating agents, such as D-penicillamine and trientine. In this study, the authors used zinc acetate to treat Japanese patients with Wilson disease and investigated its efficacy. The 37 patients that comprise this study were found to have Wilson disease using clinical and biochemical tests and were administrated zinc acetate for 48 weeks. The authors followed the clinical symptoms and laboratory findings of the patients by assessing their complete blood counts, biochemical findings, as well as the results of urinalysis and special laboratory tests for copper and zinc metabolism. We also examined side effects of the treatment. Zinc acetate did not aggravate the hepatic or neurological symptoms of any of the patients. Blood biochemical analysis also did not reveal elevation of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltranspeptidase levels. Zinc treatment did not aggravate the patients' clinical signs and/or laboratory findings. However, it did improve some clinical symptoms of the Wilson disease patients. Although this agent had some side effects, none of them were severe. The authors measured spot urinary copper excretion, which gave an indication of the efficacy of treatment and of the sufficient dosage of zinc. We recommend maintaining a spot urinary copper excretion less than 0.075-μg/mg creatinine. The authors conclude that zinc acetate is an effective and safe treatment for Japanese patients with Wilson disease., (Copyright © 2010 Mosby, Inc. All rights reserved.)

It was shown that the activity of interferon-induced enzyme 2',5'-oligoadenylate-synthetase is suppressed in rat spleen lymphocytes under the chronic alcohol intoxication. The values of enzyme activity were minimal under the long-term action of etanol (21 day). The combined administration of zinc acetate and etanol to rats causes the increase of enzyme activity, the effect is most expressed on the late stages of alcohol intoxication development.

Aims/hypothesis: Treatment with the Cu(II)-selective chelator triethylenetetramine (TETA) improves cardiovascular disease in human patients, and cardiac and vascular/renal disease in rats used as a model of diabetes. Here we tested two hypotheses: first, that TETA elicits greater improvement in organ function than less Cu-selective transition-metal-targeted treatments; second, that the therapeutic actions of TETA are consistent with mediation through suppression of oxidative stress., Methods: Rats were made diabetic with streptozotocin (55 mg/kg, i. v.) and treated from 8 weeks after disease induction for the following 8 weeks with effective dosages of oral TETA, or one of three less Cu-selective transition-metal-targeted treatments: D-penicillamine, deferiprone or Zn acetate. Treatment effects were measured in ex vivo cardiac and aortic tissues, plasma and urine., Results: Diabetes damaged both cardiac and renal/vascular function by impairing the ability of cardiac output to respond physiologically to rising afterload, and by significantly elevating the urinary albumin/creatinine ratio. Diabetes also lowered total antioxidant potential and heparan sulphate levels in cardiac and arterial tissues, and serum ferroxidase activity, whereas it elevated urinary heparan sulphate excretion. TETA treatment rectified or partially rectified all these defects, whereas the other three experimental treatments were ineffectual. By contrast, none of the four drug treatments lowered diabetes-mediated elevations of plasma glucose or lipid concentrations., Conclusions/interpretation: TETA may limit the cardiac and renal/vascular damage inflicted by diabetes through its actions to reinforce antioxidant defence mechanisms, probably acting through selective chelation of 'loosely-bound'/chelatable Cu(II). It may also improve heparan sulphate homeostasis and bolster antioxidant defence by increasing vascular extracellular superoxide dismutase activity. Urinary albumin/creatinine ratio might prove useful for monitoring TETA treatment.