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In rats, mice, and humans, it is known that zinc deficiency may be related to anemia, and zinc supplementation influences hemoglobin production. Our previous studies indicate that in fish, zinc supplementation stimulates red blood cell (RBC) formation (erythropoiesis). However, it is not clear whether the mechanism of zinc-induced erythropoiesis stimulation in fish also occurs in rats. We induced anemia in rats using phenylhydrazine (PHZ) and injected either saline or ZnSO4 solution. We found that an appropriate amount of zinc stimulated erythropoiesis in the PHZ-induced anemic rats. The effects of ZnSO4 injection were dose-dependent. When the concentration of ZnSO4 was higher than 2.8 mg zinc/kg body weight, the RBC level of the anemic rats increased from 60 ± 7% to 88 ± 10% that of the normal rats in two days. Rat bone marrow cells with or without ZnCl2 supplementation were cultured in suspension in vitro. In the cell culture when the zinc concentration was at 0.3 mM, a 1.6-fold proliferation of nascent immature reticulocytes (new RBCs) was observed after one day. In the rat blood, zinc was combined with serum transferrin to induce erythropoiesis. The stimulation of RBC formation by zinc appears to be common among different animals.

Zinc (Zn) is an essential element in the growth of all animals and plays structural and catalytic roles in many enzymes and functional proteins. Two completely randomized trials were conducted to evaluate the effects of different sources of zinc on performance, nutrient digestibility, blood mineral profile, and antioxidant enzyme activities in male growing lambs on a barley-based diet. The first trial was conducted for 70 days and consisted of 30 lambs (30.8 ± 2.8 kg mean body weight, 4–5 months of age) which were randomly allocated to five treatments consisting of a basal diet (19.72 mg Zn/kg DM), or the basal diet supplemented with 30 mg Zn/kg DM, added as either zinc-sulfate (ZnSulf; inorganic), zinc-methionine (ZnMet), zinc-proteinate (ZnProt) or zinc-glycinate (ZnGly). For the second trial, to measure the effects of dietary Zn on nutrient digestibility, four lambs from each group of the first experiment were randomly allocated to individual digestibility cages for 12 days (first 7 days as an adaptation period followed by 5 days of sample collection). Among the groups, dietary Zn supplementation above basal level significantly improved average daily gain, average daily feed intake, feed/gain ratio, and superoxide dismutase activity of red blood cells ( P  < 0.05). Glutathione peroxidase activity of lambs supplemented with organic Zn was significantly ( P  < 0.05) higher than inorganic and control groups. At the end of the trial, the concentration of plasma Zn, tri-iodothyronine (T3), thyroxine (T4), and the activity of alkaline phosphatase was increased ( P  < 0.05) in all groups receiving Zn as compared with controls ( P  < 0.05). In addition, thyroxine level in animals supplemented with Zn-methionine and Zn-proteinate was greater than in animals receiving Zn-glycine and Zn-sulfate. The results of the second trial revealed that the supplementation with Zn-methionine and Zn-proteinate increased the digestibility of crude protein (CP) and acid detergent fiber (ADF) compared to groups supplemented with Zn sulfate and control ( P  < 0.05). All organic sources of Zn improved organic matter (OM) digestibility compared to inorganic and control ( P  < 0.05). Results indicated that, regardless of source, supplementation of Zn in growing lambs improved growth performance, blood antioxidants, and thyroid hormone levels. Furthermore, Zn-methionine and Zn-proteinate supplementation appeared to improve the digestibility of CP, OM, and ADF more effectively than Zn-sulfate.

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. 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. 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. 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.

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.

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. 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. 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. 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.

Background Low-osmolarity oral rehydration salt (ORS) and zinc therapy effectively manage diarrhea in children under five years of age, offering both short- and long-term benefits. Despite this, caregivers’ adherence to ORS and zinc is often unsatisfactory due to factors such as forgetfulness, resolution of symptoms, and underestimation of the disease’s severity. This study assessed the effect of mobile call reminders on ORS and zinc tablet adherence among children with acute diarrhea in a secondary-level health facility in Kwara State, Nigeria. Methods Using an open-label, randomized controlled trial design, this study compared caregiver-child pairs with acute diarrhea aged 6–59 months who received standard instructions (SI) alone (control group) and an intervention group (IG) who received SI plus phone call reminders on days three and seven of zinc sulfate therapy. All participants used a pictorial diary to track loose/watery stools and ORS and zinc tablet treatments for ten days. The primary outcome measures were independent and combined adherence to ORS and zinc therapy. The secondary outcomes were independent and combined adherence scores, defined as the percentage of times the ORS was given post-diarrhea and the percentage of prescribed zinc tablets administered out of ten. Results A total of 364/400 mother–child pairs completed the study. The percentage of mothers with full adherence in the intervention group was 82.5% for ORS, 72.1% for zinc, and 58.5% for combined use, compared to 78.8%, 60.8%, and 43.6%, respectively, in the control group. The odds of full adherence to ORS and zinc were 1.6 and 1.7 times higher among intervention mothers [ORS: OR = 1.561, 95% CI = 0.939–2.598, P  = 0.085; zinc: OR = 1.671, 95% CI = 1.076–2.593, P  = 0.022], and 1.8 times higher for combined use according to WHO guidelines [OR = 1.818, 95% CI = 1.200–2.754, P  = 0.005]. The mean adherence scores for the intervention group were higher than those for the control group by 4.1% (95% CI = 0.60–7.60) for ORS, 7.3% (95% CI = 3.74–10.86) for zinc, and 5.7% (95% CI = 3.23–8.17) for the combined treatment. Conclusion Phone reminders can effectively improve consistency of home treatment administered by caregivers for children under five years old. Trial Registration The study was registered retrospectively (17/3/2023) with the Pan African Clinical Trial Registry (PACTR202301560735856).

Objectives To evaluate the efficacy of a toothpaste containing amine compound, 0.5% zinc lactate, and 1400 ppm F (NaF) in comparison to a regular fluoride toothpaste containing 1450 ppm F as MFP/NaF (negative control). Plaque and gingivitis indices were determined over a 6-month period. Materials and methods In a randomized, double-blind, two-cell, parallel-group design on healthy adults from the Bangkok, Thailand area presenting with initial gingivitis (Löe-Silness gingival index ≥ 1) and visible plaque (Turesky Modification-Quigley-Hein index ≥ 1.5) were assigned test and negative control toothpastes and instructed to brush twice daily for two minutes. Results Site-level ( N  = 10,778) and subject-level ( N  = 92) data indicated that the test toothpaste increased the number of healthy sites and improved gum health as compared to the negative control toothpaste. For the test group, after 6 months, the average reduction for plaque, gingival index, and gingival severity was 31.2%, 32.3%, and 49.3%, respectively. Average reductions were greater in the test group than the negative control group across all measures. Conclusions The amine + zinc + fluoride toothpaste significantly improved measures of plaque (12× more effective) and gingivitis (5× more effective) in comparison to a standard fluoride toothpaste, suggesting that the novel formulation with antibacterial active ingredients amine and zinc facilitates more effective plaque removal, and promotes gingival health. Clinical relevance These results suggest that daily use of amine + zinc + fluoride toothpaste can provide a significant improvement in managing plaque accumulation and bleeding associated with gingival inflammation especially for patients experiencing gingivitis. Clinical trial registration NCT06563518 (registration date: August 19, 2024).

Objectives To determine the efficacy of zinc sulfate supplementation in managing dysmenorrhoea. Methods In total, 103 high school students were randomised into an experimental arm (52 students) and a control arm (51 students) and received 40-mg zinc sulfate or placebo, respectively, over three cycles. Primary outcome measures were the mean Visual Analogue Scale score, which measured pain over three cycles, and the frequency of nausea and vomiting. Secondary outcomes were the use of additional analgesics and the frequency of allergic reactions. Results Fifty participants were analysed in each group. Mean pain scores were not significantly different between the groups before administering zinc sulfate therapy. Following the intervention, the mean pain scores for the treatment (2.80 ± 2.28) and placebo (3.48 ± 2.85) groups were not significantly different in the first cycle; however, scores in the treatment group were significantly better in the second (2.56 ± 1.97 vs 3.80 ± 2.77) and third (1.95 ± 1.72 vs 3.95 ± 2.82) cycles. No significant differences were observed between the groups in the nausea and vomiting incidence and the requirement for additional analgesics. Conclusions Zinc sulfate reduces dysmenorrhoea severity with minimal or no adverse effects, especially with more than one cycle of usage. Trial Registration Number: PACTR202105843292338. The trial is publicly available and was registered at www.pactr.org on 25 May 2021.

Background A significant percentage of head and neck cancer (HNCs) patients receiving RT experience oral mucositis (OM). This study aimed to evaluate the effect of the polyherbal (containing chamomile, peppermint oil, Aloe vera , and honey) and zinc mouthwashes in comparison to the control (chlorhexidine) and placebo groups for prevention of radiation-induced OM. Methods This study was a double-blinded randomized clinical trial, conducted on 67 patients with HNCs undergoing radiotherapy. The eligible participants were randomized to receive either one of the following; zinc sulfate, polyherbal, chlorhexidine (Vi-one 0.2% CHX), or placebo mouthwash for 6 weeks. Follow-up evaluation of oral hygiene and the checklists of OM and the intensity of pain were filled out according to WHO assessment tool, Oral Mucositis Assessment Scale (OMAS), and Visual Analog Scale (VAS) in all the participants weekly for seven consecutive weeks. Results The results of present clinical trial demonstrated that the use of either zinc sulfate or polyherbal mouthwash significantly reduced the scores of OM and the severity of pain during weeks 2 to 7 after consumption compared with the CHX or placebo mouthwashes ( P  < 0.05). According to the post hoc analysis and compared with the placebo, a significantly better result was reported for zinc sulfate and polyherbal mouthwashes at weeks 2 to 7, but not for the CHX mouthwash. Conclusion This study showed that the use of zinc sulfate or polyherbal mouthwashes is effective in prevention of both OM severity scores and pain related to OM intensity at weeks 2 to 7 following consumption in HNCs patients. Trial registration IRCT20190123042475N1 and IRCT20190123042475N2. Registration date: 2019-06-09, 2019-07-26.

Background: In hemodialysis (HD) patients, zinc depletion caused by inadequate intake, malabsorption, and removal by HD treatment leads to erythropoiesis-stimulating agent (ESA) hyporesponsiveness. This study investigated the effects of zinc supplementation in HD patients with zinc deficiency on changes in the erythropoietin responsiveness index (ERI). Methods: Patients on HD with low serum zinc levels (<65 μg/dL) were randomly assigned to two groups: The polaprezinc group (who received daily polaprezinc, containing 34 mg/day of zinc) (n = 35) and the control group (no supplementation) (n = 35) for 12 months. All the 70 patients had been taking epoetin alpha as treatment for renal anemia. ERI was measured with the following equation: Weekly ESA dose (units)/dry weight (kg)/hemoglobin (g/dL). Results: There were no significant changes in hemoglobin levels within groups or between the control and polaprezinc groups during the study period. Although reticulocyte counts were increased immediately after zinc supplementation, this change was transient. Serum zinc levels were significantly increased and serum copper levels were significantly decreased in the polaprezinc group after three months; this persisted throughout the study period. Although there was no significant change in the serum iron or transferrin saturation levels in the polaprezinc group during the study period, serum ferritin levels significantly decreased following polaprezinc treatment. Further, in the polaprezinc group, ESA dosage and ERI were significantly decreased at 10 months and nine months, respectively, as compared with the baseline value. Multiple stepwise regression analysis revealed that the change in the serum zinc level was an independent predictor of lowered ERI. Conclusions: Zinc supplementation reduces ERI in patients undergoing HD and may be a novel therapeutic strategy for patients with renal anemia and low serum zinc levels.