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Purpose: Erythromycin is an effective topical antibiotic for treating mild-to-moderate inflammatory acne vulgaris, especially papules acne during puberty as well as papules - pustular acne in adult women. Erythromycin is a macrolide antibiotic that has long been used as a topical dosage form to treat acne. It has favorable effects in resolving inflammatory acne lesions not only by reducing Propioni bacterium acnes density, but also by directly inhibiting neutrophil chemotactic factors and reactive oxygen species (ROS) production. Zinc, a metallic element has bacteriostatic activity against Propioni bacterium acnes. Combining zinc with antibiotic (erythromycin) can reduce antibiotic resistance and increase antibiotic absorption in-to the skin. Material and methods: In the present study, erythromycin (2% w/v) with zinc acetate (1.2% w/v) as 'topical gel' and erythromycin (2% w/v) gel alone were evaluated for treating mild to moderate inflammatory acne vulgaris. This double-blind study was carried out on 102 patients 13-25 years of age, divided into two groups. The group A received erythromycin and group B received erythromycin with zinc acetate topical gels during 3 weeks. Acne grading and lesion counts for comedones, papules and pustules were performed during each visit zero, first, second and third weeks. Results: Erythromycin treatment (with zinc acetate) gel showed to be more effective than erythromycin (alone) gel with respect to reducing the number of acne lesions and severity grade of acne.Number of lesions and severity of acne were significantly reduced at the end of 3rd week in both groups ( p < .001). Conclusions: In conclusion, it can be stated that erythromycin with and without zinc acetate was clinically effective, and both formulations produced a significant reductions in acne grading as well as inflamed and noninflamed lesion counts ( p < .000). Statistically, there was no significant difference between formulation A and B.

Background: To investigate whether pre-dialysis level of serum creatinine (SCre) could indicate the responsiveness to zinc supplementation of patients on maintenance hemodialysis (MHD)., Methods: We retrospectively reviewed the results of our previous randomized study of 91 patients who had been on MHD and received zinc supplementation with either zinc acetate hydrate (ZAH; zinc, 50 mg/day) or polaprezinc (PPZ; zinc, 34 mg/day). A late response to zinc supplementation was defined as a serum zinc level of < 80 μg/dL three months after the study began. Patients were divided into two groups: late response (serum zinc level < 80 μg/dL) and early response (serum zinc level ≥ 80 μg/dL). Factors independently associated with a late response to zinc supplementation were determined using inverse probability of treatment weighting (IPTW) multivariate logistic analysis., Results: Of 91 patients, 86 continued to receive zinc supplementation after three months. The mean pre-dialysis SCre level was 10.0 mg/dL. The number of patients with a late response and response to zinc supplementation was 32 and 54, respectively. There was a significant negative correlation between the pre-dialysis SCre and the Δserum zinc change for 3 months. (r = - 0.284, P = 0.008). IPTW multivariate analysis showed that a pre-dialysis SCre level ≥ 10.0 mg/dL (odds ratio, 3.71; 95% confidence interval; 1.24-11.1, P = 0.022) was an independent factor associated with a late response to zinc supplementation., Conclusions: Pre-dialysis SCre level was independently associated with responsiveness to zinc supplementation after three months in patients on MHD.

The essential trace element zinc maintains liver functions. Liver diseases can alter overall zinc concentrations, and hypozincemia is associated with various hepatic pathologies. Modulating systemic zinc through dietary supplementation is potentially useful for liver diseases. We evaluated the usefulness of zinc (NPC-02; acetate formulation) supplementation. We conducted two NPC-02 studies on zinc-deficient patients (serum zinc < 70 μg/dL). Study 1: double-blind, randomized, placebo-controlled trial on 57 subjects with chronic liver diseases comparing serum zinc in patients given NPC-02 (NPC-02 group) versus placebo (Placebo group). Study 2: dose adjustment study on 43 subjects with/without liver diseases to determine proportions maintaining serum zinc target (≥ 80 μg/dL but < 200 μg/dL). In study 1, NPC-02 subjects had higher serum zinc concentrations at week 8 than Placebo subjects (83.2 ± 20.2 and 61.3 ± 12.0, respectively; P < 0.0001), and more NPC-02 than Placebo subjects achieved the serum zinc target (15/27 vs. 1/26). In study 2, the NPC-02-induced serum zinc increase was dose-dependent in subjects both with and without liver diseases (r = 0.5143, P = 0.0022 and r = 0.5753, P = 0.0005, respectively). Interestingly, there was a marginally positive correlation between serum zinc and albumin levels in subjects with but not in those without liver diseases (r = 0.4028, P = 0.0631 and r = 0.1360, P = 0.5567, respectively). NPC-02 dose-dependently increases serum zinc in hypozincemic patients, regardless of liver disease. NPC-02 is a potentially effective therapy for liver cirrhosis, in which zinc deficiency is common. Clinical trial registry number: NCT02337569, NCT02321865.

Case: A 27-year-old, gravida 2, para 0, Japanese female who was maintained on zinc acetate (75 mg/day) during pregnancy expressed her desire to breastfeed after birth. We investigated the possibility of breastfeeding while on treatment. Breast milk zinc concentrations were determined using an atomic absorption photometer. Breast milk zinc concentrations on the 4 th (colostrum) and 32 nd (post-colostrum) days post partum were 10.80 μg/mL and 3.28 μg/mL, respectively. These values are less than the reported range of breast milk zinc concentrations in Japanese women who are not under any medication. Conclusion: We measured blood and breast milk zinc concentrations of a patient with Wilson's disease who was taking zinc acetate (75 mg/day). Zinc values were within the range of breast milk concentrations of mothers who are not on zinc acetate.

Wilson disease is an autosomal recessive disorder based on inborn error of copper metabolism. The copper accumulates in the liver, brain, cornea, kidney, and other organs. This disease should be considered any individual with liver abnormality except infant, any patient older than teenage with neurological (especially for extra pyramidal signs) or neuropsychiatric disorder with or without liver disease and sibling of Wilson disease patient. Typically, a combination of low serum ceruloplasmine levels and high levels of urinary copper contents is sufficient to establish a diagnosis. As other diagnostic tests, measurement of hepatic copper content and ATP7B gene analysis are available. The key strategy of treatment is to reduce the amount of copper in the liver and other tissues by administering both copper-chelating agents, such as D-penicillamine or Trientine, and/or zinc acetate. The author recommend zinc acetate monotherapy for mild to moderate hepatic disorder, Trientine mono therapy for mild to moderate neurologic disorder and combination therapy of Trientine and zinc acetate for sever hepatic or neurologic disorder.

ZnO and Zn acetate nanoparticles were embedded in polycaprolactone coaxial-fibers and uniaxial-fibers matrices to develop potential antibacterial nanocomposite wound dressings (mats). Morphology, composition, wettability, crystallinity and fiber structure of mats were characterized. Antibacterial properties of mats were tested against E. coli and S. aureus by turbidity and MTT assays. The effect of UVA illumination (prior to bacteria inoculation) on mats' antibacterial activity was also studied. Results showed that a coaxial-fibers design maintained nanoparticles distributed in the outer-shell of fibers and, in general, enhanced the antibacterial effect of the mats, in comparison to conventional uniaxial-fibers mats. Results indicated that mats simultaneously inhibited planktonic and biofilm bacterial growth by, probably, two main antibacterial mechanisms; 1) release of Zn 2+ ions (mainly from Zn acetate nanoparticles) and 2) photocatalytic oxidative processes exerted by ZnO nanoparticles. Antibacterial properties of mats were significantly improved by coaxial-fibers design and exposure to UVA-light prior to bacteria inoculation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Acne vulgaris is a chronic disease of the pilosebaceous units presenting as inflammatory or noninflammatory lesions in individuals of all ages. The current standard of treatment includes topical formulations in the forms of washes, gels, lotions, and creams such as antibiotics, antibacterial agents, retinoids, and comedolytics. Additionally, systemic treatments are available for more severe or resistant forms of acne. Nevertheless, these treatments have shown to induce a wide array of adverse effects, including dryness, peeling, erythema, and even fetal defects and embolic events. Zinc is a promising alternative to other acne treatments owing to its low cost, efficacy, and lack of systemic side effects. In this literature review, we evaluate the effectiveness and side-effect profiles of various formulations of zinc used to treat acne., (© 2017 Wiley Periodicals, Inc.)

During the postweaning period, piglets are prone to gastrointestinal infections. The resulting impairment of intestinal barrier function may cause diarrhea associated with growth retardation or even death of piglets. Orally applied Zn is commonly used to prevent and treat diarrhea, but its mode of action still needs to be elucidated. To analyze the molecular mechanism whereby Zn acts on porcine intestinal barrier function, ex vivo studies on piglet jejunum and accompanying in vitro studies on a porcine jejunal epithelial cell line, IPEC-J2/PS, were performed with electrophysiological tools. Feeding pharmacological Zn doses exerted no significant electrophysiologically ascertainable short- and long-term effects on jejunal barrier function ex vivo. However, in IPEC-J2/PS, basolateral Zn was cytotoxic since its application caused a release of lactate dehydrogenase and an irreversible breakdown of the epithelial barrier. In contrast, apical Zn application caused an immediate increase in paracellular resistance and a decrease in permeability to the paracellular marker fluorescein, reflecting overall barrier strengthening in vitro. Apical effects were fully reversible upon washout. This indicates that Zn supplemented to feed was completely washed out during ex vivo jejunum preparation. We conclude that there is no evidence for long-term barrier effects through prophylactic Zn supplementation and that extracellular Zn acts acutely and reversibly from the apical side via tightening the paracellular route, thus counteracting leak-flux diarrhea. NEW & NOTEWORTHY Therapeutically administered Zn successfully treats diarrhea in veterinary and human medicine. Here we present data that Zn strengthens the porcine jejunal epithelial barrier by reversibly tightening the paracellular route for inorganic ions and small solutes. Acute or long-lasting Zn effects on transcellular transport (Cl - secretion) were not detected. We therefore conclude that Zn is useful for acutely treating leak-flux diarrhea rather than secretory diarrhea. Suitability as prophylactic feed supplement, however, is questionable., (Copyright © 2017 the American Physiological Society.)

We previously showed that the combination of the non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 with zinc acetate (ZA) formulated in a carrageenan (CG; MZC) gel provided macaques significant protection against vaginal simian-human immunodeficiency virus-RT (SHIV-RT) challenge, better than either MIV-150/CG or ZA/CG. The MZC gel was shown to be safe in a phase 1 clinical trial. Herein, we used in vitro approaches to study the antiviral properties of ZA and the MIV-150/ZA combination, compared to other NNRTIs. Like other NNRTIs, MIV-150 has EC 50 values in the subnanomolar to nanomolar range against wild type and NNRTI or RT-resistant HIVs. While less potent than NNRTIs, ZA was shown to be active in primary cells against laboratory-adapted and primary HIV-1 isolates and HIV-1 isolates/clones with NNRTI and RT resistance mutations, with EC 50 values between 20 and 110 μM. The MIV-150/ZA combination had a potent and broad antiviral activity in primary cells. In vitro resistance selection studies revealed that previously described NNRTI-resistant mutations were selected by MIV-150. ZA-resistant virus retained susceptibility to MIV-150 (and other RTIs) and MIV-150-selected virus remained sensitive to ZA. Notably, resistant virus was not selected when cultured in the presence of both ZA and MIV-150. This underscores the potency and breadth of the MIV-150/ZA combination, supporting preclinical macaque studies and the advancement of MZC microbicides into clinical testing.

Women globally need access to multipurpose prevention technologies (MPTs) that prevent human immunodeficiency virus (HIV), sexually transmitted infections that increase HIV acquisition/transmission risk, and unintended pregnancy. Seeking an MPT with activity against HIV, herpes simplex virus-2 (HSV-2), and human papillomavirus (HPV), we developed a prototype intravaginal ring (IVR), the MZCL IVR, which released the antiviral agents MIV-150, zinc acetate, and carrageenan (MZC for short) and the contraceptive levonorgestrel (LNG). Previously, we showed that an MZC gel has potent activity against immunodeficiency viruses, HSV-2, and HPV and that the MZCL (MZC with LNG) IVR releases all four components in macaques in vivo at levels associated with efficacy. Vaginal fluid from treated macaques has in vitro activity against HIV, HSV-2, and HPV. Herein, we assessed the ability of the MZCL IVR to protect macaques against repeated co-challenge with HSV-2 and SHIV-RT (simian immunodeficiency virus [SIV] containing the reverse transcriptase gene from HIV) and prevent hormonal cycling. We evaluated in vivo drug release in co-challenged macaques by measuring drug levels in blood and vaginal fluid and residual drug levels in used IVRs. The MZCL IVR significantly prevented SHIV-RT infection, reduced HSV-2 vaginal shedding, and prevented cycling. No non-nucleoside HIV reverse transcriptase inhibitor (NNRTI)-resistant SHIV was detected in macaques that became infected after continuous exposure to MZC from the IVR. Macaques wearing the MZCL IVR also had carrageenan levels in vaginal fluid expected to protect from HPV (extrapolated from mice) and LNG levels in blood associated with contraceptive efficacy. The MZCL IVR is a promising MPT candidate that warrants further development.

Zinc level in the blood plasma and brain of rats was studied by inductively coupled plasma mass spectrometry. Maximum amount of zinc was observed in the cerebellum (15.0±5.5 μg/mg wet tissue). Single intraperitoneal administration of a zinc donor acyzol (24 mg/kg) did not change the content of this element in the tissues. Repeated injections of acyzol (7 injections over 14 days) significantly increased zinc level in rat plasma and brain. This elevation was most pronounced in the forebrain (cortex and subcortical structures). The rise in zinc concentration in blood plasma correlated with its level in the brain.

Objective: To evaluate the safety and pharmacokinetics of MIV-150 and zinc acetate in a carrageenan gel (PC-1005). Acceptability, adherence, and pharmacodynamics were also explored., Design: A 3-day open-label safety run-in (n = 5) preceded a placebo-controlled, double-blind trial in healthy, HIV-negative, abstinent women randomized (4:1) to vaginally apply 4 mL of PC-1005 or placebo once daily for 14 days., Methods: Assessments included physical examinations, safety labs, colposcopy, biopsies, cervicovaginal lavages (CVLs), and behavioral questionnaires. MIV-150 (plasma, CVL, tissue), zinc (plasma, CVL), and carrageenan (CVL) concentrations were determined with LC-MS/MS, ICP-MS, and ELISA, respectively. CVL antiviral activity was measured using cell-based assays. Safety, acceptability, and adherence were analyzed descriptively. Pharmacokinetic parameters were calculated using noncompartmental techniques and actual sampling times. CVL antiviral EC50 values were calculated using a dose-response inhibition analysis., Results: Participants (n = 20) ranged from 19-44 years old; 52% were black or African American. Among those completing the trial (13/17, PC-1005; 3/3, placebo), 11/17 reported liking the gel overall; 7 recommended reducing the volume. Adverse events, which were primarily mild and/or unrelated, were comparable between groups. Low systemic MIV-150 levels were observed, without accumulation. Plasma zinc levels were unchanged from baseline. Seven of seven CVLs collected 4-hour postdose demonstrated antiviral (HIV, human papillomavirus) activity. High baseline CVL anti-herpes-simplex virus type-2 (HSV-2) activity precluded assessment of postdose activity., Conclusions: PC-1005 used vaginally for 14 days was well tolerated. Low systemic levels of MIV-150 were observed. Plasma zinc levels were unchanged. Postdose CVLs had anti-HIV and anti-human papillomavirus activity. These data warrant further development of PC-1005 for HIV and sexually transmitted infection prevention., Competing Interests: The authors have no conflicts of interest to disclose.

Background: Pneumonia is a leading cause of morbidity and mortality in children younger than five years of age. Most deaths occur during infancy and in low-income countries. Daily zinc supplements have been reported to prevent acute lower respiratory tract infection (LRTI) and reduce child mortality. This is an update of a review first published in 2010., Objectives: To evaluate the effectiveness of zinc supplementation in the prevention of pneumonia in children aged two to 59 months., Search Methods: We searched CENTRAL (Issue 21 October 2016), MEDLINE (1966 to October 2016), Embase (1974 to October 2016), LILACS (1982 to October 2016), CINAHL (1981 to October 2016), Web of Science (1985 to October 2016) and IMSEAR (1980 to October 2016)., Selection Criteria: Randomised controlled trials (RCTs) evaluating zinc supplementation for the prevention of pneumonia in children aged from 2 months to 59 months., Data Collection and Analysis: Two review authors independently assessed trial quality and extracted data., Main Results: We did not identify any new studies for inclusion in this update. We included six studies that involved 5193 participants.Analysis showed that zinc supplementation reduced the incidence of pneumonia by 13% (fixed-effect risk ratio (RR) 0.87; 95% confidence interval (CI) 0.81 to 0.94, six studies, low-quality evidence) and prevalence of pneumonia by 41% (random-effects RR 0.59; 95% CI 0.35 to 0.99, one study, n = 609, low-quality evidence). On subgroup analysis, we found that zinc reduced the incidence of pneumonia defined by specific clinical criteria by 21% (i.e. confirmation by chest examination or chest radiograph) (fixed-effect RR 0.79; 95% CI 0.0.71 to 0.88, four studies, n = 3261), but had no effect on lower specificity pneumonia case definition (i.e. age-specific fast breathing with or without lower chest indrawing) (fixed-effect RR 0.95; 95% CI 0.86 to 1.06, four studies, n = 1932)., Authors' Conclusions: Zinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia.

We compared the preclinical safety and efficacy of tenofovir (TFV) 1% gel with that of MZC gel [containing 50 μM MIV-150, 14 mM Zn(O2CCH3)2(H2O)2, and 3% carrageenan] through a series of in vitro, ex vivo, and in vivo assays. The two gels showed good antiviral therapeutic indexes (50% cytotoxic concentration/50% effective concentration ratios; range, >25 to 800). MZC showed greater anti-simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) activity than TFV 1% gel in rhesus macaque vaginal explants. MZC protected mice from vaginal herpes simplex virus 2 (HSV-2) challenge (P < 0.0001), but the TFV 1% gel did not., (Copyright © 2016 Jean-Pierre et al.)

Women urgently need a self-initiated, multipurpose prevention technology (MPT) that simultaneously reduces their risk of acquiring HIV-1, HSV-2, and HPV (latter two associated with increased risk of HIV-1 acquisition) and prevents unintended pregnancy. Here, we describe a novel core-matrix intravaginal ring (IVR), the MZCL IVR, which effectively delivered the MZC combination microbicide and a contraceptive. The MZCL IVR contains four active pharmaceutical ingredients (APIs): MIV-150 (targets HIV-1), zinc acetate (ZA; targets HIV-1 and HSV-2), carrageenan (CG; targets HPV and HSV-2), and levonorgestrel (LNG; targets unintended pregnancy). The elastomeric IVR body (matrix) was produced by hot melt extrusion of the non-water swellable elastomer, ethylene vinyl acetate (EVA-28), containing the hydrophobic small molecules, MIV-150 and LNG. The solid hydrophilic core, embedded within the IVR by compression, contained the small molecule ZA and the macromolecule CG. Hydrated ZA/CG from the core was released by diffusion via a pore on the IVR while the MIV-150/LNG diffused from the matrix continuously for 94 days (d) in vitro and up to 28 d (study period) in macaques. The APIs released in vitro and in vivo were active against HIV-1ADA-M, HSV-2, and HPV16 PsV in cell-based assays. Serum LNG was at levels associated with local contraceptive effects. The results demonstrate proof-of-concept of a novel core-matrix IVR for sustained and simultaneous delivery of diverse molecules for the prevention of HIV, HSV-2 and HPV acquisition, as well as unintended pregnancy., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to determine the effects in Bos indicus calves of intra-testicular injection of either saline (n=9) or one of two doses of zinc acetate ((ZA1, 57.75mg, n=10, or ZA2, 71.75mg, n=10) or surgical castration (n=9) on circulating concentrations of testostosterone and liveweight. Human chorionic gonadotrophin (hCG, 1500IU) was administered 202 and 525 days after treatment on Day 0 and animals were slaughtered on Day 860. In animals left intact treatment with ZA reduced mean serum concentrations of testosterone (Saline: 5.58±0.79ng/mL, ZA1: 1.28±0.27ng/mL, ZA2: 1.01±0.17ng/mL; P<0.001) and concentrations 48h following administration of hCG. The maximum concentration of testosterone recorded throughout the study in six out of 19 animals treated with ZA was ≤0.21ng/mL. Treatment with ZA did not significantly affect live weights or carcass weights or result in any detectable scrotal lesions. Animals with concentrations of testosterone ≥1.0ng/mL exhibited greater liveweights throughout most of the study and yielded heavier carcass weights (340.9±7.02 versus 309.3±6.17kg, P=0.002). It is concluded that a single, intra-testicular administration of either 57.75mg or 71.75mg of ZA was able to similarly reduce circulating concentrations of testosterone without significantly affecting liveweights or carcass weights. Treatment with ZA can result in variation in circulating concentrations of testosterone which could lead to differences in behaviour, liveweights and carcass characteristics., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: A previous meta-analysis found that high dose zinc acetate lozenges reduced the duration of common colds by 42%, whereas low zinc doses had no effect. Lozenges are dissolved in the pharyngeal region, thus there might be some difference in the effect of zinc lozenges on the duration of respiratory symptoms in the pharyngeal region compared with the nasal region. The objective of this study was to determine whether zinc acetate lozenges have different effects on the duration of common cold symptoms originating from different anatomical regions., Methods: We analyzed three randomized trials on zinc acetate lozenges for the common cold administering zinc in doses of 80-92 mg/day. All three trials reported the effect of zinc on seven respiratory symptoms, and three systemic symptoms. We pooled the effects of zinc lozenges for each symptom and calculated point estimates and 95% confidence intervals (95% CI)., Results: Zinc acetate lozenges shortened the duration of nasal discharge by 34% (95% CI: 17% to 51%), nasal congestion by 37% (15% to 58%), sneezing by 22% (-1% to 45%), scratchy throat by 33% (8% to 59%), sore throat by 18% (-10% to 46%), hoarseness by 43% (3% to 83%), and cough by 46% (28% to 64%). Zinc lozenges shortened the duration of muscle ache by 54% (18% to 89%), but there was no difference in the duration of headache and fever., Conclusions: The effect of zinc acetate lozenges on cold symptoms may be associated with the local availability of zinc from the lozenges, with the levels being highest in the pharyngeal region. However our findings indicate that the effects of zinc ions are not limited to the pharyngeal region. There is no indication that the effect of zinc lozenges on nasal symptoms is less than the effect on the symptoms of the pharyngeal region, which is more exposed to released zinc ions. Given that the adverse effects of zinc in the three trials were minor, zinc acetate lozenges releasing zinc ions at doses of about 80 mg/day may be a useful treatment for the common cold, started within 24 hours, for a time period of less than two weeks.

Aims/hypothesis: SLC30A8 encodes a zinc transporter in the beta cell; individuals with a common missense variant (rs13266634; R325W) in SLC30A8 demonstrate a lower early insulin response to glucose and an increased risk of type 2 diabetes. We hypothesised that zinc supplementation may improve insulin secretion in a genotype-dependent manner., Methods: We evaluated the early insulin response to glucose (using frequently sampled intravenous glucose tolerance testing) by R325W genotype before and after 14 days of supplementation with oral zinc acetate (50 mg elemental zinc) twice daily in healthy non-diabetic Amish individuals (N = 55)., Results: Individuals with RW/WW genotypes (n = 32) had the lowest insulin response to glucose at 5 and 10 min at baseline (vs RR homozygotes [n = 23]). After zinc supplementation, the RW/WW group experienced 15% and 14% increases in the insulin response to glucose at 5 and 10 min, respectively (p ≤ 0.04), and, compared with RR homozygotes, experienced a 26% (p = 0.04) increase in insulin at 5 min. We observed reciprocal decreases in proinsulin:insulin in the RW/WW (p = 0.002) vs RR group (p = 0.048), suggesting a genotype-specific improvement in insulin processing., Conclusions/interpretation: Zinc supplementation appears to affect the early insulin response to glucose differentially by rs13266634 genotype and could be beneficial for diabetes prevention and/or treatment for some individuals based on SLC30A8 variation., Trial Registration: ClinicalTrials.gov NCT00981448.

To extend our observations that single or repeated application of a gel containing the NNRTI MIV-150 (M) and zinc acetate dihydrate (ZA) in carrageenan (CG) (MZC) inhibits vaginal transmission of simian/human immunodeficiency virus (SHIV)-RT in macaques, we evaluated safety and anti-SHIV-RT activity of MZC and related gel formulations ex vivo in macaque mucosal explants. In addition, safety was further evaluated in human ectocervical explants. The gels did not induce mucosal toxicity. A single ex vivo exposure to diluted MZC (1∶30, 1∶100) and MC (1∶30, the only dilution tested), but not to ZC gel, up to 4 days prior to viral challenge, significantly inhibited SHIV-RT infection in macaque vaginal mucosa. MZC's activity was not affected by seminal plasma. The antiviral activity of unformulated MIV-150 was not enhanced in the presence of ZA, suggesting that the antiviral activity of MZC was mediated predominantly by MIV-150. In vivo administration of MZC and CG significantly inhibited ex vivo SHIV-RT infection (51-62% inhibition relative to baselines) of vaginal (but not cervical) mucosa collected 24 h post last gel exposure, indicating barrier effect of CG. Although the inhibitory effect of MZC (65-74%) did not significantly differ from CG (32-45%), it was within the range of protection (∼75%) against vaginal SHIV-RT challenge 24 h after gel dosing. Overall, the data suggest that evaluation of candidate microbicides in macaque explants can inform macaque efficacy and clinical studies design. The data support advancing MZC gel for clinical evaluation.

We have previously reported that Zn(2+) infused into the coronary arteries of isolated rat hearts leads to the potent dephosphorylation of phospholamban (PLB) as well as a noticeable but less potent dephosphorylation of the ryanodine receptor 2. We hypothesized in the present study that a Zn(2+)-activated phosphatase is located in the vicinity of the sarcoplasmic reticulum (SR) where PLB and ryanodine receptor 2 reside. We report here the novel finding of tissue-nonspecific alkaline phosphatase (TNAP), a zinc-dependent enzyme, localized to the SR in the cardiac sarcomere of mouse myocardium. TNAP activity was enhanced by injection of Zn acetate into a tail vein before harvesting the heart and imaged using electron microscopy of electron dense deposits indicative of the hydrolysis of exogenous β-glycerophosphate. TNAP activity was observed localized to the ends of the Z-line corresponding to SR and was qualitatively more visible in myocardium of males compared with females. Correspondingly, PLB phosphorylation status was potently reduced in myocardium of males injected with Zn acetate, whereas there was no apparent effect of Zn acetate injection on PLB phosphorylation in females. Surprisingly, Western blot analysis of TNAP content suggested a significantly lower TNAP content in males compared with females. These data suggest that TNAP plays a role in governing the phosphorylation status of calcium handling proteins in the SR. Furthermore, the content and activity of TNAP are differentially regulated between the sexes and thus may account for some sex differences in cardiopathologies associated with calcium handling., (Copyright © 2014 the American Physiological Society.)

The aggregation of amyloid-β in Alzheimer's disease can be affected by free transition metals such as copper and zinc in the brain. Addition of copper and zinc with amyloid acts to increase aggregation and copper additionally promotes the formation of reactive oxygen species. We propose that reduction of brain copper by blocking uptake of copper from the diet is a viable strategy to regulate the formation of insoluble amyloid-β in the brain of Tg2576 mice. Mice were treated with regimens of zinc acetate, which acts with metallothionein to block copper uptake in the gut, at various times along their lifespan to model prevention and treatment paradigms. We found that the mice tolerated zinc acetate well over the six month course of study. While we did not observe significant changes in cognition and behavior, there was a reduction in insoluble amyloid-β in the brain. This observation coincided with a reduction in brain copper and interestingly no change in brain zinc. Our findings show that blocking copper uptake from the diet can redistribute copper from the brain and reduce amyloid-β aggregation.

We previously showed that a prototype gel comprising zinc acetate (ZA) in carrageenan (CG) protected mice against vaginal and rectal herpes simplex virus 2 (HSV-2) challenge as well as macaques against vaginal simian-human immunodeficiency virus reverse transcriptase (SHIV-RT) challenge. In this work, we modified buffers and cosolvents to obtain a stable, nearly iso-osmolal formulation and evaluated its safety and efficacy against SHIV-RT and HSV-2. In vitro toxicity to lactobacilli and Candida albicans was determined. Macaques were given daily doses of ZA and CG (ZA/CG) or CG alone vaginally for 14 days and challenged with SHIV-RT 24 h later. Mice were challenged vaginally or rectally with HSV-2 immediately after a single gel treatment to measure efficacy or vaginally 12 h after daily gel treatment for 7 days to evaluate the gel's impact on susceptibility to HSV-2 infection. The modified ZA/CG neither affected the viability of lactobacilli or C. albicans nor enhanced vaginal HSV-2 infection after daily ZA/CG treatment. Vaginal SHIV-RT infection of macaques was reduced by 66% (P = 0.006) when macaques were challenged 24 h after the last dose of gel. We observed 60% to 80% uninfected mice after vaginal (P < 0.0001) and rectal (P = 0.008) high-dose HSV-2 challenge. The modified ZA/CG gel is safe and effective in animal models and represents a potential candidate to limit the transmission of HIV and HSV-2.

The present study was undertaken to establish mode of action, comparative therapeutic efficacy and safety evaluation of dithiothreitol (DTT) supplemented with Zn and Se against dimethylmercury in rats. Adult male albino rats of Sprague-Dawley strain (150±10 g, n=6 per group) were exposed a bolus dose of dimethylmercury (10 mg/kg, p.o.) for once only followed by DTT (15.4 mg/kg, i.p.) along with the combination of antioxidants Zn and Se (2 mmol/kg and 0.5 mg/kg, p.o.) after 72 h of toxicant administration for three days. The results showed a significant (P≤0.05) increase in the activities of AST, ALT, alkaline phosphatase, lactate dehydrogenase, in serum after toxicant administration. This was accompanied by histopathological observations. A significant rise was observed in lipid peroxidation level and mercury ion concentration however reduced glutathione content decreased in liver, kidney and brain. A significant (P≤0.05) decrease in the activity of acetyl cholinesterase was also seen in different regions of brain. Combined treatment of DTT along with Zn and Se significantly (P≤0.05) recouped the alterations in the enzymatic activities of serum and reversed the tissue biochemical and histopathological changes of liver, kidney and brain. Our results demonstrate that combined treatment of thiol chelator (DTT) along with antioxidants (Zn and Se) plays an important role against dimethylmercury induced tissue damage and hepatic, nephro and neurotoxicity., (Copyright © 2013. Published by Elsevier GmbH.)

Background: Haemoglobinopathies, inherited disorders of haemoglobin synthesis (thalassaemia) or structure (sickle cell disease), are responsible for significant morbidity and mortality throughout the world. The WHO estimates that, globally, 5% of adults are carriers of a haemoglobin condition, 2.9% are carriers of thalassaemia and 2.3% are carriers of sickle cell disease. Carriers are found worldwide as a result of migration of various ethnic groups to different regions of the world. Zinc is an easily available supplement and intervention programs have been carried out to prevent deficiency in people with thalassaemia or sickle cell anaemia. It is important to evaluate the role of zinc supplementation in the treatment of thalassaemia and sickle cell anaemia to reduce deaths due to complications., Objectives: To assess the effect of zinc supplementation in the treatment of thalassaemia and sickle cell disease., Search Methods: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of most recent search: 01 February 2013., Selection Criteria: Randomised, placebo-controlled trials of zinc supplements for treating thalassaemia or sickle cell disease administered at least once a week for at least a month., Data Collection and Analysis: Two review authors assessed the eligibility and risk of bias of the included trials, extracted and analysed data and wrote the review. We summarised results using risk ratios or rate ratios for dichotomous data and mean differences for continuous data. We combined trial results where appropriate., Main Results: We identified nine trials for inclusion with all nine contributing outcome data. Two trials reported on people with thalassaemia (n = 152) and seven on sickle cell anaemia (n = 307).In people with thalassaemia, in one trial, the serum zinc level value showed no difference between the zinc supplemented group and the control group, mean difference 47.40 (95% confidence interval -12.95 to 107.99). Regarding anthropometry, in one trial, height velocity was significantly increased in patients who received zinc supplementation for one to seven years duration, mean difference 3.37 (95% confidence interval 2.36 to 4.38) (total number of participants = 26). In one trial, however, there was no difference in body mass index between treatment groups.Zinc acetate supplementation for three months (in one trial) and one year (in two trials) (total number of participants = 71) was noted to increase the serum zinc level significantly in patients with sickle cell anaemia, mean difference 14.90 (95% confidence interval 6.94 to 22.86) and 20.25 (95% confidence interval 11.73 to 28.77) respectively. There was no significant difference in haemoglobin level between intervention and control groups, at either three months (one trial) or one year (one trial), mean difference 0.06 (95% confidence interval -0.84 to 0.96) and mean difference -0.07 (95% confidence interval -1.40 to 1.26) respectively. Regarding anthropometry, one trial showed no significant changes in body mass index or weight after one year of zinc acetate supplementation. In patients with sickle cell disease, the total number of sickle cell crises at one year were significantly decreased in the zinc sulphate supplemented group as compared to controls, mean difference -2.83 (95% confidence interval -3.51 to -2.15) (total participants 130), but not in zinc acetate group, mean difference 1.54 (95% confidence interval -2.01 to 5.09) (total participants 22). In one trial at three months and another at one year, the total number of clinical infections were significantly decreased in the zinc supplemented group as compared to controls, mean difference 0.05 (95% confidence interval 0.01 - 0.43) (total number of participants = 36), and mean difference -7.64 (95% confidence interval -10.89 to -4.39) (total number of participants = 21) respectively., Authors' Conclusions: According to the results, there is no evidence from randomised controlled trials to indicate any benefit of zinc supplementation with regards to serum zinc level in patients with thalassaemia. However, height velocity was noted to increase among those who received this intervention.There is mixed evidence on the benefit of using zinc supplementation in people with sickle cell disease. For instance, there is evidence that zinc supplementation for one year increased the serum zinc levels in patients with sickle cell disease. However, though serum zinc level was raised in patients receiving zinc supplementation, haemoglobin level and anthropometry measurements were not significantly different between groups. Evidence of benefit is seen with the reduction in the number of sickle cell crises among sickle cell patients who received one year of zinc sulphate supplementation and with the reduction in the total number of clinical infections among sickle cell patients who received zinc supplementation for both three months and for one year.The conclusion is based on the data from a small group of trials,which were generally of good quality, with a low risk of bias. The authors recommend that more trials on zinc supplementation in thalassaemia and sickle cell disease be conducted given that the literature has shown the benefits of zinc in these types of diseases.

We describe a case of nephrotic syndrome (NS) after a 7 months treatment with D-penicillamine in a 14 years old girl with Wilson's disease, with a prompt regression at the discontinuation of the drug. Kidney function, proteinuria in particular, must be always monitored during the chelating therapy, and the drug must be discontinued as soon as signs of renal injury are detected.

Wilson's disease (WD) is not as rare as once believed, and has a wide range of presentations with equally wide range of age of onset. Sometimes the primary presentation might be unusual and may require a thorough investigation to avoid a misdiagnosis. Our case presented with uncontrolled seizures, severe hypokalemia, renal failure, and hypoparathyroidism. After being diagnosed as WD and treated for the same patient made a remarkable recovery.

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.

The aim of this study was to develop and study floating controlled drug delivery systems consisting of a model drug (zinc acetate dihydrate), different forms of a matrix-forming polymer (Metolose 90 SH) and sodium bicarbonate as an effervescent component. The proportions of Metolose and bicarbonate were varied, and the effects of the different ratios on the properties of the resulting powders and tablets were determined. The water uptakes of different powder mixtures were initially evaluated. These tests indicated the interaction of the active and effervescent agent, this phenomenon leading to an unpredicted increase in the amount of liquid taken up. This interaction was evaluated as concerns the degradation of the hydrophilic matrix system. The disintegration of tablets with different compositions revealed that this interaction increases the time required for the disintegration of these systems. The study demonstrated that the interaction of the components induced significant changes in the parameters of this new sensitive delivery system. In the last steps, the buoyancy and dissolution properties of tablets that appeared appropriate for the formulation of a controlled drug delivery system were investigated., (Copyright © 2010 Elsevier B.V. All rights reserved.)

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: Pneumonia is a leading cause of morbidity and mortality in children younger than five years of age. Most deaths occur during infancy and in low-income countries. Daily regimens of zinc have been reported to prevent acute lower respiratory tract infection and reduce child mortality., Objectives: To evaluate the effectiveness of zinc supplementation in the prevention of pneumonia in children aged two to 59 months., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 2), which contains the Acute Respiratory Infections Group's Specialised Register, MEDLINE (1966 to January Week 2, 2010), EMBASE (1974 to January 2010) and LILACS (1985 to January 2010)., Selection Criteria: Randomised controlled trials (RCTs) evaluating supplementation of zinc for the prevention of pneumonia in children aged 2 to 59 months of age., Data Collection and Analysis: Two review authors independently assessed trial quality and extracted data., Main Results: We included six trials and 7850 participants in the meta-analysis. Analysis showed that zinc supplementation reduced the incidence of pneumonia by 13% (risk ratio (RR) 0.87; 95% confidence interval (CI) 0.81 to 0.94, fixed-effect, six studies) and prevalence of pneumonia by 41% (RR 0.59; 95% CI 0.35 to 0.99, random-effects, one study). On subgroup analysis, we found that zinc reduced the incidence of pneumonia defined by specific clinical criteria by 21% (i.e. confirmation by chest examination or chest radiograph) (RR 0.79; 95% CI 0.0.71 to 0.88, fixed-effect, four studies, n = 4591) but had no effect on lower specificity pneumonia case definition (i.e. age specific fast breathing with or without lower chest indrawing) (RR 0.95; 95% CI 0.86 to 1.06, fixed-effect, four studies, n = 3259)., Authors' Conclusions: Zinc supplementation in children is associated with a reduction in the incidence and prevalence of pneumonia, the leading cause of death in children.

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.

Iron and zinc are essential for normal brain function, yet the mechanisms used by astrocytes to scavenge non-transferrin-bound iron (NTBI) and zinc are not well understood. Ischaemic stroke, traumatic brain injury and Alzheimer's disease are associated with perturbations in the metabolism of NTBI and zinc, suggesting that these two metals may collectively contribute to pathology. The present study has investigated the accumulation of NTBI and zinc by rat primary astrocyte cultures. It was found that astrocytes express mRNA for both divalent metal transporter 1 (DMT1) and Zip14, indicating the potential for these transporters to contribute to the accumulation of NTBI and zinc by these cells. Astrocytes were found to accumulate iron from ferric chloride in a time- and dose-dependent manner, and the rate of accumulation was strongly stimulated by co-incubation with zinc acetate. In addition, cultured astrocytes rapidly accumulated zinc from zinc acetate, and this accumulation was stimulated by co-incubation with ferric chloride. Because a synergistic stimulation of iron and zinc accumulation is inconsistent with the known properties of DMT1 and Zip14, the present results suggest that additional mechanisms assist astrocytes to scavenge iron and zinc when they are present together in the extracellular compartment. These mechanisms may be involved in disorders that involve elevations in the extracellular concentrations of these metal ions.

We report a case of a 24-year-old man who presented with a complaint of reduced mouth opening and a burning sensation. On examination, he was clinically diagnosed with oral submucous fibrosis (OSF). Following routine biopsy and histopathological confirmation of OSF, the patient was supplemented with zinc acetate along with vitamin A and was followed up for 4 months. Following treatment the patient reported increased mouth opening and a reduced burning sensation. Histopathologically re-epithelialisation was evident along with the appearance of normal rete pegs. The data for mouth opening, collagen content and epithelial thickness of six other cases similarly treated are also presented, showing a significant increase in mouth opening and epithelial thickness and decrease in collagen content. We propose the use of zinc acetate and vitamin A for the management of OSF.

Background: Wilson's disease (WD) is an autosomal recessive defect of cellular copper export. Early diagnosis in children is difficult due to its obscure clinical presentations. The efficacy of zinc salts is well documented, although there are limited data concerning zinc use in pediatric patients with WD., Methods: We performed a retrospective analysis of clinical features, laboratory results and treatment responses in children with WD diagnosed at Taichung Veterans General Hospital between 1996 and 2008. Diagnosis was established by low serum ceruloplasmin, high 24-hour urinary copper excretion, presence of Kayser-Fleischer rings, and mutation analysis., Results: Eleven children were included in this study. The main initial presentations were impaired liver function tests (6/11) and hemolytic anemia (2/11). Gene studies in seven children showed six different mutations (G934D, R778Q, C490X, 304insC, IVS4-1 G > C, P992I) and one possible novel mutation (L1181P). All patients had improved liver function tests and hemoglobin levels after treatment with D-penicillamine, trientine and zinc supplement therapy. During a mean period of 3.4 +/- 2.1 years with zinc therapy, six patients had serum zinc levels above the normal limit, and seven patients had serum copper levels below the normal range., Conclusion: Serum ceruloplasmin and 24-hour urinary copper examinations could be used to rule out WD in children with chronic hepatitis and hemolytic anemia. Gene analysis is helpful for prompt diagnosis of asymptomatic siblings and patients with atypical features. Zinc treatment is generally safe in pediatric patients with WD. However, its adverse effects should be monitored., (Copyright 2010 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Necrolytic acral erythema (NAE) is a distinct skin entity and is strongly associated with chronic hepatitis C virus (HCV) infection. It is distinguished by its acral location, typical clinical and histopathologic features, and positive serum antibodies against HCV. Most cases have been treated with variable success using oral zinc, amino acids, and interferon with or without ribavirin therapy., Methods: We report two patients with the clinical and histopathologic features of NAE; however, both tested seronegative for HCV. Both patients were treated with oral zinc acetate with good response, with one showing a partial relapse after stopping oral zinc. The clinical features, histopathologic findings, association of HCV, and treatment of NAE in different case reports were reviewed., Conclusion: NAE has a strong association with HCV, particularly in prevalent countries such as Egypt. Nevertheless, it may occur independently without HCV association, and oral zinc may prove to be a less toxic therapeutic option for such cases.

Intracellular levels of zinc have shown a strong inverse correlation to growth and malignancy of prostate cancer. To date, studies of zinc supplementation in prostate cancer have been equivocal and have not accounted for bioavailability of zinc. Therefore, we hypothesized that direct intra-tumoral injection of zinc could impact prostate cancer growth. In this study, we evaluated the cytotoxic properties of the pH neutral salt zinc acetate on the prostate cancer cell lines PC3, DU145 and LNCaP. Zinc acetate killed prostate cancer cell lines in vitro, independent of androgen sensitivity, in a dose-dependent manner in a range between 200 and 600 microM. Cell death occurred rapidly with 50% cell death by six hours and maximal cell death by 18 hours. We next established a xenograft model of prostate cancer and tested an experimental treatment protocol of direct intra-tumoral injection of zinc acetate. We found that zinc treatments halted the growth of the prostate cancer tumors and substantially extended the survival of the animals, whilst causing no detectable cytoxicity to other tissues. Thus, our studies form a solid proof-of-concept that direct intra-tumoral injection of zinc acetate could be a safe and effective treatment strategy for prostate cancer.

Background: Zinc lozenges have been used for treatment of the common cold; however, the results remain controversial., Methods: Fifty ambulatory volunteers were recruited within 24 h of developing symptoms of the common cold for a randomized, double-blind, placebo-controlled trial of zinc. Participants took 1 lozenge containing 13.3 mg of zinc (as zinc acetate) or placebo every 2-3 h while awake. The subjective scores for common cold symptoms were recorded daily. Plasma zinc, soluble interleukin (IL)-1 receptor antagonist (sIL-1ra), soluble tumor necrosis factor receptor 1, soluble vascular endothelial cell adhesion molecule, and soluble intercellular adhesion molecule (sICAM)-1 were assayed on days 1 and 5., Results: Compared with the placebo group, the zinc group had a shorter mean overall duration of cold (4.0 vs. 7.1 days; P < .0001) and shorter durations of cough (2.1 vs. 5.0 days; P < .0001) and nasal discharge (3.0 vs. 4.5 days, P = .02) Blinding of subjects was adequate, and adverse effects were comparable in the 2 groups. Symptom severity scores were decreased significantly in the zinc group. Mean changes in plasma levels of zinc, sIL-1ra, and ICAM-1 differed significantly between groups., Conclusion: Administration of zinc lozenges was associated with reduced duration and severity of cold symptoms. We related the improvement in cold symptoms to the antioxidant and anti-inflammatory properties of zinc.

Background: Antibiotics are often combined with other agents to provide topical acne treatments that are effective against both inflammatory and non-inflammatory lesions and minimize the development of antibiotic resistance., Objectives: To compare the clinical effectiveness of two combination treatments for facial acne: a ready mixed, once daily gel containing clindamycin phosphate (1%) plus benzoyl peroxide (5%) (CDP + BPO) and a twice daily solution of erythromycin (4%) plus zinc acetate (1.2%) (ERY + Zn)., Methods/patients: In this assessor-blind, randomized study, 73 patients were treated with CDP + BPO once daily and 75 patients with ERY + Zn twice daily. The treatment period was 12 weeks and lesion counts and global improvement were assessed at weeks 1, 2, 4, 8 and 12., Results: CDP + BPO showed an earlier onset of action with a faster significant reduction in total lesion counts than ERY + Zn. The proportion of patients with at least a 30% improvement in non-inflammatory lesions at week 1 was 31.5% for CDP + BPO and 17.3% for ERY + Zn; the corresponding percentages for inflammatory lesions were 39.7% and 29.3%. A difference was also observed at week 2 (53.4% vs. 36.0% for non-inflammatory lesions and 72.6% vs. 53.3% for inflammatory lesions). The trend in favour of CDP + BPO, although less marked, continued to the end of the study, with reductions in the total lesion count at endpoint of 69.8% for CDP + BPO group and 64.5% for ERY + Zn group. Both treatments were well tolerated., Conclusions: CDP + BPO and ERY + Zn are effective treatments for acne but CDP + BPO has an earlier onset of action that should improve patient compliance.

Objective: This project was designed to evaluate the effects of melatonin and zinc on the glycemic control in type 2 diabetes mellitus (T2DM) patients with inadequate response to the oral hypoglycemic agent metformin., Methods: A placebo controlled, double-blind clinical trial was performed at the Specialized Center for Endocrinology and Diabetes, Al-Rusafa Directorate of Health, Baghdad, Iraq during the period from February to July 2005, in which 46 type 2 diabetic patients were selected and allocated into 3 groups, these groups were treated with single daily oral doses of both 10 mg melatonin and 50 mg zinc acetate alone; 10 mg melatonin and 50 mg zinc acetate in addition to the regularly used metformin or placebo, given at bed time for 90 days. We measured the fasting plasma glucose (FPG), glycated hemoglobin (HbA1C) and serum C-peptide before starting the treatment (zero time) and after 30 and 90 days of treatment. We also performed post-prandial glucose excursion test (PPGE) for selected patients from the second and third groups before starting the treatment and after 90 days., Results: Daily administration of melatonin and zinc improved the impaired fasting and post-prandial glycemic control and decreased the level of glycated hemoglobin; addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent., Conclusion: The combination of melatonin and zinc acetate, when used alone or in combination with metformin improves fasting and post-prandial glycemic control in T2DM patients.

Glycemic control and prevention of secondary complications are the most important goals of using pharmacologic treatment of diabetes mellitus (DM). The inadequate responses to oral hypoglycemic agents may be attributed to inadequate postreceptor events even when insulin levels are quite sufficient, and associated with oxidative stress induced by long-term hyperglycemia. The administration of antioxidants such as melatonin and zinc may improve tissue responses to insulin and increase the efficacy of drugs, e.g. metformin, which act through this pathway. This project was designed to evaluate the effects of melatonin and zinc on the lipid profile and renal function in type 2 DM patients poorly controlled with metformin. A placebo-controlled, double-blind clinical trial was performed in which 46 type 2 diabetic patients were selected and allocated into three groups. These groups were treated with single daily oral doses of both 10 mg of melatonin and 50 mg of zinc acetate alone: 10 mg of melatonin and 50 mg of zinc acetate in addition to the regularly used metformin or placebo, given at bedtime for 90 days. Fasting lipid profiles and microalbuminuria (MAU) were measured before initiating the treatments (zero time) and after 30 and 90 days of treatment. Daily administration of melatonin and zinc improved the impaired lipid profile and decreased the level of MAU; the addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent. In conclusion, the combination of melatonin and zinc acetate, when used alone or in combination with metformin, improves DM-related complications such as the impaired lipid profile and MAU in type 2 DM patients.

Background/aims: Gingipains, proteolytic enzymes produced by the periodontal pathogen Porphyromonas gingivalis, are regarded as virulence factors in the pathogenesis of periodontitis. Inhibition of gingipain activity therefore may have therapeutic potential, and it has been suggested that chlorhexidine may inhibit the activities of these enzymes. The purposes of the present study were to examine systematically the inhibitory effects of chlorhexidine on three purified gingipains and to determine the effect of Zn(II) on chlorhexidine inhibition., Methods: The activities of lys-gingipain (Kgp) and two forms of arg-gingipain (RgpB and HRgpA) were measured in the presence of varying concentrations of chlorhexidine and with chlorhexidine supplemented with Zn(II). Inhibition constants (K(i)'s) were determined for chlorhexidine alone and in the presence of Zn(II). Fractional inhibitory constant indices were calculated to assess the synergy of the chlorhexidine-Zn(II) inhibition., Results: RgpB, HRgpA, and Kgp were all inhibited by chlorhexidine with K(i)'s in the micromolar range. For RgpB and HRgpA, the inhibitory effects of chlorhexidine were enhanced 3-30-fold by Zn(II). The chlorhexidine-Zn(II) interaction was synergistic for inhibition of HRgpA and RgpB. For Kgp, the effect of Zn(II) on chlorhexidine inhibition was antagonistic., Conclusions: Chlorhexidine is an effective inhibitor of gingipains, and the inhibition of R-gingipains is enhanced by Zn(II). A mixture of chlorhexidine and Zn(II) may be useful as an adjunct in the treatment of periodontitis and in the post-treatment maintenance of periodontitis patients.

Background: Acne vulgaris is an extremely common skin disorder that can be treated effectively with drugs that are currently available. Poor compliance, however, is a major factor in the high failure rates seen in acne treatment. Compliance might be enhanced by considering patient preferences for acne medications. Conjoint analysis is well suited for the study of patient preferences in healthcare, but is novel to the field of dermatology., Objectives: The study aimed to determine and compare patient preferences for four topical antibiotics used for 1 week, once or twice daily, to treat acne vulgaris., Methods: A randomised, phase IV, single-centre, cross-over study was performed using conjoint analysis and a traditional patient questionnaire. Over 4 weeks, the patients used each of four topical antibiotics for 1 week: erythromycin/zinc solution, clindamycin phosphate lotion, benzoyl peroxide (BP)/erythromycin gel (each applied twice daily) and clindamycin phosphate gel (applied once daily). The conjoint analysis examined five different attributes of acne medications: form, storage, product life once opened, method of application and regimen (each with two or three possible options). From 108 possible permutations of the five attributes, 16 hypothetical medications were selected at random and described on printed cards. Pre- and post-treatment, the patients ranked the cards in order of preference and rated each hypothetical product based on their likelihood to use it. For each patient, product 'utilities' were then calculated by multiple regression. The patients also completed a patient acceptability questionnaire, by which they rated the product acceptability after 1 week of treatment with each of the four topical antibiotics. The patients later ranked the medications in order of preference after using all four treatments. Adverse events were recorded in diary cards to assess tolerability., Results: Of 67 patients recruited, 64 used all four medications and completed the study. The conjoint analysis found that a gel formulation, room temperature storage, product life of up to 18 months once opened, application with fingers and once-daily regimen were the options ranked first for the five product attributes. According to the ranking order (out of 108) for the combination of attributes representing the four study medications, clindamycin phosphate gel had the highest rankings (6 and 1 pre- and post-treatment, respectively) and BP/erythromycin gel had the lowest rankings (93 and 70 pre- and post-treatment). The rankings of clindamycin phosphate lotion and erythromycin/zinc solution worsened from pre- to post-treatment, indicating a shift in patient preference after they experienced products 'in-use' during the study. Based on the questionnaire, clindamycin phosphate gel was liked best by the highest proportion of patients (33%). In terms of overall satisfaction, the order of preference was: (i) clindamycin phosphate gel, (ii) clindamycin phosphate lotion, (iii) BP/erythromycin gel and (iv) erythromycin/zinc solution. Adverse events related to medication occurred most frequently with erythromycin/zinc solution and BP/erythromycin gel. Clindamycin phosphate gel was the only product not associated with any episodes resulting in a change of medication or dose., Conclusions: Conjoint analysis provided a convenient, reliable tool for assessing patient preferences for topical antibiotics used to treat acne. The patients clearly preferred a gel formulation that could be applied with the fingers once daily and stored at room temperature for as long as 18 months. One product (clindamycin phosphate gel) combined all five of the preferred attributes, a preference confirmed by the simulated product rankings. These findings of the conjoint analysis are consistent with the safety profiles and the results of the traditional questionnaire.

Zinc/clindamycin gel (Zindaclin 1%) gel, is a new once-daily topical acne treatment (Strakan Ltd) containing clindamycin phosphate equivalent to 1% clindamycin and zinc acetate in a formulation, which leads to a reduced systemic absorption of clindamycin through the skin. The objective of the study was to compare the systemic absorption of clindamycin from zinc/clindamycin gel and clindamycin lotion (Dalacin T topical lotion, Pharmacia Ltd) after repeated twice-daily topical administration for two periods of 5 days with an intervening gap of 2 weeks in 24 subjects with mild to moderate acne. Plasma Cmax, and AUC0-12 of clindamycin measured after single and multiple applications of zinc/clindamycin gel were between 30% and 50% lower than for clindamycin lotion. As zinc/clindamycin gel is a topical treatment for acne, the lower systemic bioavailability may be beneficial because there may be a correspondingly lower risk of systemic events in zinc/clindamycin gel-treated subjects.

Background: Mucosal damage by H. pylori infection is mainly caused by neutrophils producing large quantities of reactive oxygen species (ROS). Metallothionein (MT) an intracellular, low-molecular, cysteine-rich protein, which is inducible by dietary zinc (Zn), has been implicated in sequestering ROS. This study examines the effects of Zn supplementation on Helicobacter colonisation and associated gastritis and the relationship with gastric MT levels., Methods: C57Bl/6 mice were inoculated with either 10(8) H. pylori or H. felis and were infected for 4 weeks or 6 and 12 weeks, respectively. Mice infected with H. pylori (4 weeks) or H. felis (6 weeks) were treated with either Zn acetate (ZnA; 1 mg/ml), or Zn sulphate (ZnSO4; 5 mg/ml) for 2 weeks with 0.1 ml oro-gastric gavage twice daily. H. pylori load and H. felis colonisation density were determined by culture and microscopy, respectively. MT levels and H. felis-induced gastritis were also determined., Results: Zn treatment showed no significant difference in Helicobacter load and gastric MT, however, ZnSO4 treatment showed a significant (p<0.05) increased in gastric MT in H. felis infected mice. Both Zn-treated groups showed a significant (p<0.05) difference in gastritis score in the antrum of the stomach within the basal and submucosal compartments compared to H. felis-infected controls., Conclusions: We found that H. felis-induced gastritis can be attenuated by short-term treatment of Zn. This observation suggests that Zn alone may be effective for the suppression of gastric mucosal inflammation induced by Helicobacter.

Introduction: A topical acne treatment in which clindamycin phosphate equivalent to 1% clindamycin is presented in a gel formulation has received marketing authorizations in a number of EU and non-EU countries. Clindamycin/zinc gel contains zinc acetate in a formulation that reduces systemic absorption of clindamycin through the skin., Objectives: To compare the efficacy and safety of a 1% clindamycin/zinc gel when applied to the face once daily or twice daily with a 1% clindamycin lotion applied twice daily for 16 weeks in patients with mild to moderate acne vulgaris., Methods: This was a randomized, comparative, observer-blind, parallel-group, multicentre study involving 246 acne patients., Results: The study demonstrated therapeutic similarity between clindamycin/zinc gel applied once and twice daily with clindamycin lotion applied twice daily. All three regimens produced a gradual and time-dependent reduction in inflamed lesions, non-inflamed lesions and overall grade. Side effects were similar and minimal, consisting predominantly of mild irritant dermatitis. All regimes produced a time-related significant reduction in skin surface and follicular Propionibacterium spp. and Micrococcaceae. The emergence of resistant strains was less than 5% and was similar with all three regimes., Conclusion: The equivalent efficacy and safety of clindamycin/zinc gel either once or twice daily to clindamycin lotion twice daily has been demonstrated. It is suggested that a treatment regime of one application per day may significantly enhance compliance and thus treatment success in acne patients.