ZINC



Table of Contents
image Effect of zinc supplementation in fracture healing
image A multicenter clinical trial. Zinc acexamate versus famotidine in the treatment of acute duodenal ulcer. Study Group of Zinc acexamate (new UP doses)
image Endogenous zinc concentrations in cysteamine-induced duodenal ulcers in the rat.
image Necrolytic migratory erythema and zinc deficiency
image Wound healing: The role of the mast cell as a zinc carrier
image Serum protein and zinc levels in patients with thoracic empyema
image Protection by zinc against UVA- and UVB-induced cellular and genomic damage in vivo and in vitro
image Prevention of the inhibitory effect of intraperitoneal 5-FU on intestinal anastomosis by zinc
image The management of lower-extremity ulcers with zinc-saline wet dressings versus normal saline wet dressings
image Lipid peroxidation in insulin-dependent diabetic patients with early retina degenerative lesions: Effects of an oral zinc supplementation
image Carcinogenicity of oral cadmium in the male Wistar (WF/NCr) rat: Effect of chronic dietary zinc deficiency
image Zinc, vitamin A and prostatic cancer
image The impact of zinc supplementation on Schistosoma mansoni reinfection rate and intensities: a randomized, controlled trial among rural Zimbabwean schoolchildren.
image Increased pancreatic metallothionein and glutathione levels: protecting against cerulein- and taurocholate-induced acute pancreatitis in rats.
image Zinc administration prevents wasting in stressed mice.
image Pathogenic mechanisms in familial amyotrophic lateral sclerosis due to mutation of Cu, Zn superoxide dismutase.
image Clinical evaluation of in-feed zinc bacitracin for the control of porcine intestinal adenomatosis in growing/fattening pigs.
image The role of metals in ischemia/reperfusion injury of the liver.
image Plasma copper, zinc and magnesium levels in patients with premenstrual tension syndrome
image The pineal and regulation of fibrosis: pinealectomy as a model of primary biliary cirrhosis: Roles of melatonin and prostaglandins in fibrosis and regulation of T lymphocytes
image Zinc, copper and magnesium concentration in serum and CSF of patients with neurological disorders
image Expression and regulation of brain metallothionein.
image Studies on the mechanism of early onset macular degeneration in c ynomolgus monkeys. II. Suppression of metallothionein synthesis in the retina in oxidative stress
image Association of zinc and antioxidant nutrients with age-related maculopathy.
image Oral zinc and the second eye in age-related macular degeneration.
image Zinc deficiency: Changes in cytokine production and T-cell subpopulations in patients with head and neck cancer and in noncancer subjects
image Immunotherapy of leprosy
image Immune and nutritional recovery of severely malnourished children
image Cellular and humoral immunity in rats after gestational zinc or magnesium deficiency
image Effects of short-term zinc supplementation on cellular immunity, respiratory symptoms, and growth of malnourished Equadorian children
image The immuno-reconstituting effect of melatonin or pineal grafting and its relation to zinc pool in aging mice.
image The pathogenesis of eclampsia: the 'magnesium ischaemia' hypothesis.
image Serum calcium, magnesium, copper and zinc and risk of cardiovascular death.
image [Evaluation of selected parameters of zinc metabolism in patients with primary hypertension]
image Antioxidant status and lipid peroxidation in patients infected with HIV
image Zinc in etiology of periodontal disease.
image ZINC AND SANGUINARIA
image Supplementation or loca1 application may reduce gingival exudate from inflammed and infected gums - which suggests improved tissue health. (Folate mouthwash appears to to be more effective than oral folate.)
image Evidence of a relationship between childhood-onset type I diabetes and low groundwater concentration of zinc
image Zinc lozenges reduce the duration of common cold symptoms
image The age-associated decline in immune function of healthy individuals is not related to changes in plasma concentrations of beta-carotene, retinol, alpha-tocopherol or zinc
image How does zinc modify the common cold? Clinical observations and implications regarding mechanisms of action
image Zinc for treating the common cold: review of all clinical trials since 1984.
image Zinc gluconate lozenges for treating the common cold. A randomized, double-blind, placebo-controlled study [see comments]
image In vivo anti-influenza virus activity of a zinc finger peptide.
image Evaluation of zinc complexes on the replication of rhinovirus 2 in vitro.
image Zinc gluconate and the common cold: a controlled clinical study.
image Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges.
image Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study.
image Zinc in different tissues: Relation to age and local concentrations in cachexia, liver cirrhosis and long-term intensive care
image Effect of antioxidants on adriamycin-induced microsomal lipid peroxidation.
image The prevention and management of pressure ulcers
image Gastrointestinal infections in children
image Effect of topical zinc oxide on bacterial growth and inflammation in full-thickness skin wounds in normal and diabetic rats.
image Bronchial reactivity and dietary antioxidants
image Decreased Cu,Zn-SOD activity in asthmatic airway epithelium: Correction by inhaled corticosteroid in vivo
image Asthma but not smoking-related airflow limitation is associated with a high fat diet in men: Results from the population study 'Men born in 1914'
image Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium
image Trace elements in prognosis of myocardial infarction and sudden coronary death
image The biological significance of zinc
image [Deficiency of certain trace elements in children with hyperactivity]
image Antioxidant status of hypercholesterolemic patients treated with LDL apheresis
image The role of free radicals in disease
image Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide
image Alzheimers disease/alcohol dementia: Association with zinc deficiency and cerebral vitamin B12 deficiency
image Rationales for micronutrient supplementation in diabetes.

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Serum calcium, magnesium, copper and zinc and risk of cardiovascular death.

Eur J Clin Nutr (ENGLAND) Jul 1996, 50 (7) p431-7

OBJECTIVE: To study the association of serum calcium, magnesium, copper and zinc concentrations with cardiovascular mortality. DESIGN: A nested case-control study within a prospective population study. SUBJECTS AND METHODS: 230 men dying from cardiovascular diseases and 298 controls matched for age, place of residence, smoking and follow-up time. Mean follow-up time was 10 years. Serum calcium, magnesium, copper and zinc concentrations were determined from samples kept frozen at -20 degrees C. RESULTS: High serum copper and low serum zinc concentrations were significantly associated with an increased mortality from all cardiovascular diseases and from coronary heart disease in particular. The relative risk of coronary heart disease mortality between the highest and lowest tertiles of serum copper and zinc were 2.86 (P = 0.03) and 0.69 (P = 0.04), respectively. Adjustment for social class, serum cholesterol, body mass index, hypertension and known heart disease at baseline examination did not materially alter the results. No significant differences were observed in concentrations of serum calcium and magnesium between cases and controls. CONCLUSIONS: High serum copper and low serum zinc are associated with increased cardiovascular mortality whereas no association was found with serum calcium and magnesium and mortality risk.



[Evaluation of selected parameters of zinc metabolism in patients with primary hypertension]

Pol Arch Med Wewn (POLAND) Mar 1996, 95 (3) p198-204

The aim of the study was to investigate the role of zinc (Zn) in essential hypertension (EH). PATIENTS AND METHODS: Material of the study consisted of 31 patients (12 female, 19 male) with mild and moderate EH and 20 healthy persons (NT) (7 female, 13 male). Erythrocyte (ZnE) and serum (ZnS) zinc as well as 24 hour urinary zinc excretion (ZuU) were assessed in both groups. Zn parameters were measured by atomic absorption spectrophotomery. RESULTS: ZnS was lower and ZnE was higher in EH (p < 0.001) than in normotensives. ZnU did not differ between EH and NT. ZnE and ZnS negatively correlated with age in NT but not in EH, ZnU negatively correlated with age only in EH. BP positively correlated with ZnS in EH but not in NT. In both groups negative correlations were found between BP and ZnU. CONCLUSIONS: 1. Zinc probably plays a role in pathogenesis of essential hypertension.



Antioxidant status and lipid peroxidation in patients infected with HIV

CHEM.-BIOL. INTERACT. (Ireland), 1994, 91/2-3 (165-180)

Deficiency in antioxidant micronutrients have been observed in patients with AIDS. These observations concerning only some isolated nutrients demonstrate a defect in zinc, selenium, and glutathione. An increase in free radical production and lipid peroxidation has been also found in these patients, and takes a great importance with recent papers presenting an immunodeficiency and more important an increase in HIV-1 replication secondary to free radicals overproduction. We have assessed different studies, trying to obtain a global view of the antioxidant status of these patients. In adults we observe a progressive decrease for zinc, selenium, and vitamin E with the severity of disease, except that selenium remains normal at stage II. However, the main dramatic decrease concerns carotenoids whose level at stage II is only half the normal value. To understand if these decreases in antioxidant and increases in oxidative stress occur secondary to the aggravation of the disease or, conversely, are responsible for it, we undertook a longitudinal survey of asymptotic patients. The preliminary results of this evaluation are presented. Paradoxically, lipid peroxidation is higher at stage II than at stage IV. This may be consecutive to a more intense overproduction of oxygen free radicals by more viable polymorphonuclear (PMN) at the asymptomatic stage. The free radicals production and lipid peroxidation seem secondary to a direct induction by the virus of PMN stimulation and cytokines secretion. N-Acetyl cystein or ascorbate have been demonstrated in cell culture to be capable of blocking the expression of HIV-1 after oxidative stress and N-acetyl cysteine inhibits in vitro TNF-induced apoptosis of infected cells. In regard to all these experimental data, few serious and large trials of antioxidants have been conducted in HIV-infected patients, although some preliminary studies using zinc or selenium have been performed. In our opinion it is now time to evaluate in humans the beneficial effect of antioxidants. The more promising candidates for presenting synergistic effects when associated with N-acetyl cysteine seem to be beta-carotene, selenium and zinc.



Zinc in etiology of periodontal disease.

Med Hypotheses (ENGLAND) Mar Stomatological Clinic, Medical 1993, 40 (3) p182-5

Microbial plaque is the main etiological factor of periodontal disease. The bacterial polysaccharides stimulate gingival neutrophils and macrophages to interleukin-1 (IL-1) production. IL-1 causes a complex of redistribution processes with liver as the central organ. Accumulation of zinc in liver and their copper and ceruloplasmin production also elicits increase of copper and decrease of zinc in gingiva. The elevated level of copper in connection with zinc deficiency in gingiva causes the increase of permeability of gingival epithelium for bacteria. The stimulated inflammatory infiltrate produces more IL-1 and the vicious circle is complete.



ZINC AND SANGUINARIA

J Periodontg1 61(6):352-8, 1990)

Experimental Placebo-controlled Study: 60 pts. with moderate plaque and gingivitis were given toothpaste and oral rinse which randomly contained either sanguinaria extract and zinc chloride or placebo and were followed for 28 weeks. Active 8p. scores were signiDcantly lower (p<0.001) than placebo scores at each post-baseline time point for all indices, with the exception of plaque at 2 weeks. The 28-wk. active 8p. scores were 21% lower than the controls for bleeding on probing. 3/30 active 8p. pts. exhibited minor soft tissue irritations that resolved spontaneously without discontinuation of product use (Harper DS et al. Clinical efficacy of a dentifrice and oral rinse containng sanguinaria extract and zinc chloride during 6 months of use.



Supplementation or loca1 application may reduce gingival exudate from inflammed and infected gums - which suggests improved tissue health. (Folate mouthwash appears to to be more effective than oral folate.)

J Clin Periodonlol 14(6):315-9, 1987)

Experimental Double-bliod Study: 60 pts with visible gingivitis rinsed for I min. twice daily with either 5 ml of 0.1% folate solution (1 mg/ml) or a placebo. After 4 wks., the folate 8p. was significantly improved compared to the placebo group. Dietary folate did not correlate with treatment results, suggesting a local effect (Pack ARC. Folate mouthwash: Effects on established gingivitis in periodontal patients. J Clin Periodontol 11:619-28, 1984).

Experimental Double-blind Study: 30 women in their 32nd wk. of pregnancy randomly received either placebo mouthwash and placebo tablets (Gp. A), placebo mouthwash 1 min. twice daily and folate 5 mg/d (Gp. B), or a 1% folate mouthwash and placebo tablets (Gp. C). After 28 days, folate levels increased signif~cantly in Gps. B and C. Gp. C showed a highly significant improvement in a gingival index despite no significant changes in a plaque index (p<0.01) while there were no significant changes in Gps. A or B (Thomson ME, Pack ARC. Effects of extended systemic and topical folate supplementation on gingivitis of pregnancy. J Clin periodontal 9(3):27580, 1982).

Experimental Double-blind Study: 30 women in their 4th or 8th mot of pregnancy randomly received either placebo mouthwash 1 min. twice daily and placebo tablets (Gp. A), placebo mouthwash and folate 5 mg/d (Gp. B), or 1% folate mouthwash and placebo tablets (Gp. C). The gingival index tended to increase throughout pregnancy in all gas. except Gp C, for whom there was a highly significant improvement in the 8th mot despite no change in plaque index. Compared to Gps. A and B, dietary intake of folate was significantly higher in Gp. C in the 8th mot (p<O.Ol) (Pack ARC, Thomson ME. Effects of topical and systemic folic acid supplementation on gingivitis in pregnancy. J Clin Periodontol 7(5):402-14, 1980).

Experimental Double-blind Study: 30 pts. with normal fasting blood folate levels rinsed their mouths daily with 5 cc of a 1 mg/cc folate solution or placebo. After 60 days, experimental subjects showed significant improvement in gingival health compare to controls (Vogel Rl et al. The effect of topical application of folic acid on gingival health. J Oral Med 33(1):20-22,1978).

Experimental Study: Contraceptive users with normal plasma folate levels demonstrated improved gingival health after receiving supplementation with folic acid 4 mg/d for 60 days (Vogel Rl et al. J Prev Dent 6:221, 1980).

Experimental Double-blind Study: 30 ptS. ingested either folic acid 2 mg twice daily or placebo. After 30 days, based on plaque and gingival indices, folic acid supplementation appeared to increase the resistance of the gingiva to local irritants leading to a reduction in inflammation. Plasma folate levels, which were normal, were unaffected by supplementation (Vogel Rl e' al. The effect of folic acid on gingival health. J periodontol 47(11):667-8, 1976).



Evidence of a relationship between childhood-onset type I diabetes and low groundwater concentration of zinc

Diabetes Care (USA), 1996, 19/8 (873-875)

OBJECTIVE - Zinc deficiency ha shown to increase the risk for diabetes in diabetes-prone experimental animals. Low concentrations of zinc have also been shown in serum of recent onset cases with IDDM. The present study examines the hypothesis that exposure to a low concentration of zinc in drinking water could increase the risk for future onset of IDDM. RESEARCH DESIGN AND METHODS - Using the Swedish childhood diabetes registry and data on residence 3 years before the onset of disease, a case-control study was designed comparing cases and control subjects with estimates of groundwater contents of zinc obtained in biogeochemical samples from areas of residence. RESULTS - A high groundwater concentration of zinc was associated with a significant decrease in risk (odds ration (OR) = 0.8; 95% CI = 0.7-0.9). The same OR was obtained when the model included information of other metals that might act as possible confounders (chromium, vanadium, cobalt selenium, cadmium, lead, and mercury). In small rural areas, in which drinking water is taken from local wells and thus is closely associated with the groundwater content within the area, an even stronger association between zinc and diabetes (OR = 0.6; 95% CI = 0.4-0.9) was found. CONCLUSIONS - It is concluded that this study for the first time provides evidence that a low groundwater content of zinc, which may reflect long-term exposure through drinking water, is associated with later development of childhood onset diabetes.



Zinc lozenges reduce the duration of common cold symptoms

Nutrition Reviews (USA), 1997, 55/3 (82-85):

A randomized, double-blind, placebo-controlled clinical trial has shown that treatment of the common cold with zinc gluconate lozenges resulted in a significant reduction in duration of symptoms of the cold. Patients received zinc-containing lozenges or placebo lozenges every 2 hours for the duration of cold symptoms. The median time to complete resolution of cold symptoms was 4.4 days in the zinc group compared with 7.6 days in the placebo group. The mechanism of action of zinc in treating the common cold remains unknown.



The age-associated decline in immune function of healthy individuals is not related to changes in plasma concentrations of beta-carotene, retinol, alpha-tocopherol or zinc

Mechanisms of Ageing and Development (Ireland), 1997, 94/1-3 (55-69)

The decline in the lymphoproliferative response to mitogenic stimuli shows marked heterogeneity in elderly individuals. Adequate nutriture is required for optimal immune function, yet nutritional status may be compromised in the elderly. To address whether this variation in the proliferative response of elderly individuals is related to their nutritional status, we studied 61 elderly (80.5 plus or minus 5.7 year-old) and 27 young (27.3 plus or minus 3.8 year-old) individuals participating in an ongoing assessment of their immune response to influenza vaccine. Ambulatory elderly individuals were recruited from five different retirement communities and were in good health upon enrollment in the study. Thirty-three percent of young and 54% of elderly subjects reported consuming micronutrient supplements daily during the study. Plasma and peripheral blood mononuclear cells (PBMC) were isolated from fasting individuals twice, 4-6 weeks apart. At both times, proliferative responses to the mitogens phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) were significantly lower (P < 0.004) in the elderly compared to the young. However, at both times, elderly participants had plasma concentrations of beta-carotene, retinol, alpha-tocopherol and zinc that were either significantly greater than, or equal to, those of young subjects. No significant correlations between plasma concentrations of beta-carotene, retinol, alpha-tocopherol and zinc and level of proliferative responses to each stimuli were observed in elderly individuals at either time. Thus, the heterogeneity in the proliferative response to mitogenic stimuli exhibited by a healthy elderly population cannot be attributed to differences in these nutritional parameters.



How does zinc modify the common cold? Clinical observations and implications regarding mechanisms of action

Medical Hypotheses (United Kingdom), 1996, 46/3 (295-302)

Clinical studies have shown that ionic zinc (Zn2+) dissolved in the mouth shortened manifestations of the common cold significantly, by an unknown mechanism. The observed immediate effect on symptoms is consonant with osmotic transport of Zn2+, placing a temporary chemical clamp on critical nerves. It is proposed that transient elevation of Zn2+ concentration in and around the nasal cavity facilitates Zn2+ complexation with known intercellular adhesion molecule binding sites on rhinovirus surfaces which prevents rhinovirus binding to cells and interrupts infection. The crystallographically determined surface of rhinovirus-14 has been found to contain binding sites for at least 360 Zn2+. Such binding of Zn2+ would be stabilized by numerous histidine, methionine, tyrosine and carboxyl/carboxylate groups known to line the HRV-14 surface canyons. The resulting blockage of HRV docking with intercellular adhesion molecule binding sites is proposed to be responsible for the observed reduction of the duration of colds by statistically significant and clinically meaningful times.



Zinc for treating the common cold: review of all clinical trials since 1984.

Altern Ther Health Med (UNITED STATES) Nov 1996, 2 (6) p63-72,

All eight publications since 1984 that have reported a total of 10 clinical studies of the treatment of common colds with zinc are reviewed. The reasons for the puzzling mix of diametrically opposite results in these studies are elucidated and related to independent in vitro investigations. A theoretical framework is put forth that explains the beneficial effects of zinc and that has a solid foundation based on the known molecular structures of the surface of human rhinovirus and intercellular adhesion molecule-1, the docking point for human rhinovirus present on the surfaces of cells of the nasal epithelium. The results of clinical investigations and theory suggest that consistently beneficial therapeutic effects can be expected of zinc ions from zinc gluconate with glycine in lozenges prepared according to homeopathic principles and procedures. The latest study published used an "intent to treat" statistical model, and the highly beneficial effects of zinc found in that study could not be compared directly with results from any earlier studies. Raw data from that study were therefore reanalyzed on the basis of assessable patients, and the results show an even better effect and can be compared directly with earlier findings. No side effects or adverse experiences due to zinc that were serious, disturbing, or persistent were found in any of the 10 studies.



Zinc gluconate lozenges for treating the common cold. A randomized, double-blind, placebo-controlled study [see comments]

Ann Intern Med (UNITED STATES) Jul 15 1996, 125 (2) p81-8, Comment in Ann Intern Med 1996 Jul 15;125(2):142-4

BACKGROUND. The common cold is one of the most frequent human illnesses and is responsible for substantial morbidity and economic loss. No consistently effective therapy for the common cold has been well documented, but evidence suggests that several possible mechanisms may make zinc an effective treatment. OBJECTIVE. To test the efficacy of zinc gluconate lozenges in reducing the duration of symptoms caused by the common cold. DESIGN. Randomized, double-blind, placebo-controlled study. SETTING. Outpatient department of a large tertiary care center. PATIENTS. 100 employees of the Cleveland Clinic who developed symptoms of the common cold within 24 hours before enrollment. INTERVENTION. Patients in the zinc group (n = 50) received lozenges (one lozenge every 2 hours while awake) containing 13.3 mg of zinc from zinc gluconate as long as they had cold symptoms. Patients in the placebo group (n = 50) received similarly administered lozenges that contained 5% calcium lactate pentahydrate instead of zinc gluconate. MAIN OUTCOME MEASURES. Subjective daily symptom scores for cough, headache, hoarseness, muscle ache, nasal drainage, nasal congestion, scratchy throat, sore throat, sneezing, and fever (assessed by oral temperature). RESULTS. The time to complete resolution of symptoms was significantly shorter in the zinc group than in the placebo group (median, 4.4 days compared with 7.6 days; P < 0.001). The zinc group had significantly fewer days with coughing (median, 2.0 days compared with 4.5 days; P = 0.04), headache (2.0 days and 3.0 days; P = 0.02), hoarseness (2.0 days and 3.0 days; P = 0.02), nasal congestion (4.0 days and 6.0 days; P = 0.002), nasal drainage (4.0 days and 7.0 days; P < 0.001), and sore throat (1.0 day and 3.0 days; P < 0.001). The groups did not differ significantly in the resolution of fever, muscle ache, scratchy throat, or sneezing. More patients in the zinc group than in the placebo group had side effects (90% compared with 62%; P < 0.001), nausea (20% compared with 4%; P = 0.02), and bad-taste reactions (80% compared with 30%; P < 0.001), CONCLUSION. Zinc gluconate in the form and dosage studied significantly reduced the duration of symptoms of the common cold. The mechanism of action of this substance in treating the common cold remains unknown. Individual patients must decide whether the possible beneficial effects of zinc gluconate on cold symptoms outweigh the possible adverse effects.



In vivo anti-influenza virus activity of a zinc finger peptide.

Antimicrob Agents Chemother (UNITED STATES) Mar 1997, 41 (3) p687-92

Matrix protein (M1) is a major structural protein of influenza virus, and it inhibits its own polymerase. A 19-amino-acid peptide, corresponding to a zinc finger region of the M1 sequence of influenza virus strain A/PR/8/34 (H1N1), centered around amino acids 148 to 166, was synthesized. This peptide, designated peptide 6, represents a zinc finger which includes a 7-amino-acid loop or finger and a 4-amino-acid tail at the carboxyl terminus, in addition to the 8 amino acids involved in the coordination of Zn. Three experiments were run to evaluate the activity of peptide 6 on infections induced in mice by influenza A/PR/8/34 and A/Victoria/3/75 (H3N2) viruses. Intranasal (i.n.) treatment of the H1N1 virus infection with 30 or 60 mg/kg of body weight/day, three times daily for 5 days, beginning 4 h pre-or 8 h post-virus exposure, was effective in preventing death, reducing the arterial oxygen decline, and inhibiting lung consolidation. Virus titers in the lungs determined on day 5 were reduced by up to 1.5 log10 in treated groups, but considerable variation in the titers of the recovered virus was seen. The H3N2 virus infection was treated i.n. with 30, 60, or 120 mg of peptide 6/kg/day by using the above-mentioned delayed initiation treatment schedule, and similar protection was seen, although lung virus titers were not reduced in the day-5 assay. Peptide 6 was well tolerated at doses up to 60 mg/kg/day. This zinc finger peptide may provide a new class of antivirals effective against influenza virus.



Evaluation of zinc complexes on the replication of rhinovirus 2 in vitro.

Res Commun Chem Pathol Pharmacol (UNITED STATES) Dec 1989

The effect of zinc salts and complexes were evaluated on the replication of rhinovirus 2 in vitro. Zinc chloride inhibited the replication of rhinovirus 2 at concentrations between 3 and 12 micrograms/ml. Influenza virus was not affected. A number of zinc complexes were tested and compared to zinc chloride. The results indicated that the activity and toxicity of all zinc complexes in the rhinovirus cytopathogenic effect (CPE) assay were directly related to the amount of unbound zinc available.



Zinc gluconate and the common cold: a controlled clinical study.

J Int Med Res (ENGLAND) Jun 1992, 20 (3) p234-46

A report in 1984 on the success of zinc gluconate against common cold symptoms could not be confirmed in three subsequent studies, which are now known to have used formulations that inactivated zinc. A non-chelating formulation including glycine, which releases 93% of contained zinc into saliva, was tested in a randomized, placebo-controlled, double-blind trial in 73 young adults. Efficacy was recorded in symptom diaries using a symptom severity rating. Patients' symptoms first appeared 1.34 days prior to entry to the study in both groups. Disappearance of symptoms occurred after an additional 4.9 days for zinc-treated patients versus 6.1 days for placebo-treated patients. A difference was noted in the efficacy of treatment if it was started 1 day after symptom onset: cold duration was an additional 4.3 days in zinc-treated patients compared with 9.2 days for placebo-treated patients. Cough, nasal drainage and congestion were the symptoms most affected, and only mild side-effects were noted.



Prophylaxis and treatment of rhinovirus colds with zinc gluconate lozenges.

J Antimicrob Chemother (ENGLAND) Dec 1987

Following a tolerance study, double-blind placebo controlled trials were conducted to determine the prophylactic effect of zinc gluconate lozenges on rhinovirus challenge and, in a third study, their therapeutic efficacy when given at the start of colds caused by virus inoculation was tested. In the prophylaxis study a total of 57 volunteers received lozenges of either zinc gluconate (23 mg) (29 volunteers) or matched placebo (28 volunteers) every 2 h while awake during a period of four and a half days. They were challenged with 10(2) tissue culture infecting dose (TCID50) of human rhinovirus 2 (HRV-2) on the second day of medication, and were monitored daily for symptoms and signs of colds and laboratory evidence of infection. Zinc reduced the total mean clinical score from 8.2 in the placebo group to 5.7 and the reduction of the mean clinical score was statistically significant on the second day after virus challenge. In the therapeutic study 69 volunteers were inoculated with 10(2) TCID50 of HRV-2 and those who developed cold symptoms were randomly allocated to receive either zinc gluconate lozenges (six volunteers) or matched placebo lozenges (six volunteers) every two hours they were awake for six days. Treatment of colds with zinc reduced the mean daily clinical score and this was statistically significant on the fourth and fifth day of medication. Similarly, medication also reduced the mean daily nasal secretion weight and total tissue count and these reductions were statistically significant on days two and six for nasal secretion weights and days four to six of medication for tissue counts when compared with placebo.



Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study.

Antimicrob Agents Chemother (UNITED STATES) Jan 1984, 25 (1) p20-4

As a possible treatment for common colds, we tested zinc gluconate lozenges in a double-blind, placebo-controlled, clinical trial. One 23-mg zinc lozenge or matched placebo was dissolved in the mouth every 2 wakeful h after an initial double dose. After 7 days, 86% of 37 zinc-treated subjects were asymptomatic, compared with only 46% of 28 placebo-treated subjects (P = 0.0005). Side effects or complaints were usually minor and consisted mainly of objectionable taste and mouth irritation. Zinc lozenges shortened the average duration of common colds by about 7 days.



Zinc in different tissues: Relation to age and local concentrations in cachexia, liver cirrhosis and long-term intensive care

INFUSIONSTHER. KLIN. ERNAHR. (SWITZERLAND), 1979, 6/4 (225-229)

Zinc concentrations in autopsy material of human heart muscle, skeletal muscle, iliac crest, pancreas and liver were analyzed by atomic absorption spectrophotometry. Age dependent differences of zinc concentrations are seen in the liver. High values show liver of premature infants, a minimum is measured in childhood which is followed by an increase in adult and old patients. The other organs show no significant changes. Different diseases like diabetes or liver cirrhosis do not influence the zinc concentration in skeletal muscle and iliac crest. Long-term intensive care patients show a marked decrease in zinc concentration of the heart muscle. In the cirrhotic liver the zinc pool is depleted. In diabetes mellitus zinc concentration of the whole pancreas is normal, in cachexia it is critically decreased.



Effect of antioxidants on adriamycin-induced microsomal lipid peroxidation.

Biol Trace Elem Res. 1995 Jan-Mar. 47(1-3). P 111-6

Adriamycin (25 microM) stimulated NADPH-dependent microsomal lipid peroxidation about fourfold over control values. The tested antioxidants, zinc, superoxide dismutase, vitamin E, and desferrioxamine (Desferal) inhibited Adriamycin-enhanced lipid peroxidation to varying degrees. Others antioxidants, e.g., glutathione, catalase, and selenium, were found to have no effects. Our in vitro studies suggest that adriamycin effect is mediated by a complex oxyradical cascade involving superoxide, hydroxyl radical, and small amounts of iron.



The prevention and management of pressure ulcers

MED. CLIN. NORTH AM. (USA), 1989, 73/6 (1511-1524)

Pressure ulcers are a common problem for older persons. Complications associated with pressure ulcers include infection and even death for some patients. Pressure is the primary pathogenic factor, but shearing forces, friction, and moisture are also important. Immobility, nutritional status, and age-related factors seem to be significant risk factors. Preventive care includes use of assessment tools to identify high risk patients, frequent repositioning, air or foam mattresses that reduce pressure over bony prominences, as well as careful attention to optimizing the overall patient condition. When pressure ulcers do develop, the treatment plan should include adequate nutrition including protein, vitamin C, and zinc supplements as indicated; systemic antibiotics for sepsis, cellulitis, osteomyelitis, or the prevention of bacterial endocarditis; and local wound care that eliminates necrotic tissue, decreases bacterial load, and provides a physiologic, pressure-free environment allowing the wound to heal. Specialized beds may be considered in some patients, particularly those with larger ulcers. Surgery is an option in older persons who are operative candidates. For some patients with pressure ulcers, appropriate treatment goals may focus on providing comfort rather than curing the ulcer.



Gastrointestinal infections in children

CURR. OPIN. GASTROENTEROL. (United Kingdom), 1994, 10/1 (88-97)

Gastrointestinal infections are common and important in infants and young children, particularly where poor hygiene and living conditions allow the spread of infectious agents. With increasing information about microorganisms that cause these infections and improved methods to detect them, many episodes that were once undiagnosed can now be attributed to previously unrecognized viruses, bacteria, and other pathogens. These advances facilitate better management and will permit more effective control and preventive strategies. This review highlights some recent reports about enterovirulent classes of Escherichia coli, including E. coli O157:H7, which causes the hemolytic-uremic syndrome and hemorrhagic colitis; Campylobacter species and a new Campylobacter-like organism (Arcobacterbutzlerlli Helicobacter pylori; Aeromonas species; and rotavirus. Important new information about intestinal parasites, including Giardia and Cryptosporidium, has emerged that should prove of practical use in diagnosis and management in places where these parasites are prevalent in children, particularly in parts of the world where HIV infection has become established. A newly described organism, so far called coccidian-like or cyanobacterium-like body, has been found in patients with prolonged diarrhea (including travelers and expatriate residents) in several countries; the name Cyclospora cayetanensis has been proposed for this organism. This year's review concludes with a short commentary on some recent reports about risk factors that predispose children to gastrointestinal infections, eg, nutritional status, domestic hygiene, maternal hygiene behavior, and young children gathered in communal facilities like day care centers. Immune function status is also important, and deficiencies of single nutrients such as vitamin A, pyridoxine, folic acid, iron, and zinc may also play a role.



Effect of topical zinc oxide on bacterial growth and inflammation in full-thickness skin wounds in normal and diabetic rats.

Eur J Surg (SWEDEN) Feb 1991, 157 (2) p97-101

The effects of topical zinc oxide on bacterial growth and inflammation were studied in full-thickness excised cutaneous wounds in normal rats and in hyperglycemic alloxan-diabetic rats. Two concentrations of zinc oxide in a gauze compress (15 or 60 mg/g) were applied to the wounds of the normal rats, but only the higher concentration was used for the diabetic rats. The polymorphonuclear leukocyte count, the alkaline phosphatase activity and bacterial counts in the granulation tissue were recorded on postoperative day 4. In the normal rats there was no significant intergroup difference in polymorphonuclear leukocyte density, though alkaline phosphatase activity was significantly depressed in those treated with the higher zinc oxide concentration. Bacterial growth in granulation tissue decreased at both zinc oxide concentrations. None of these effects was found in the diabetic rats. The results indicate that hyperglycemic diabetic rats respond differently to local zinc oxide treatment than do normal rats, and that the antibacterial activity of zinc oxide in vivo is not solely due to a direct toxic effect on the bacteria.



Bronchial reactivity and dietary antioxidants

Thorax (United Kingdom), 1997, 52/2 (166-170)

Background - It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants. Methods - The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity. Results - Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than five-fold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity. Conclusions - This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.



Decreased Cu,Zn-SOD activity in asthmatic airway epithelium: Correction by inhaled corticosteroid in vivo

American Journal of Physiology - Lung Cellular and Molecular Physiology (USA), 1997, 272/1 16-1 (L148-L154)

To investigate the antioxidant response of respiratory epithelium to the chronic airway inflammation in asthma, the major intracellular antioxidants (copper and zinc-containing superoxide dismutase (Cu,Zn-SOD) and manganese- containing SOD (Mn-SOD), catalase, and glutathione peroxidase) were quantitated in bronchial epithelial cells of healthy control and asthmatic individuals. Although catalase and glutathione peroxidase in bronchial epithelium of asthmatics were similar to control, SOD activity in asthmatics not on inhaled corticosteroid (-CS) was lower than asthmatics on inhaled corticosteroid were similar among asthmatics -CS, asthmatics +CS, and controls. Importantly, Cu,Zn-SOD specific activity in asthmatics CS was decreased in comparison with control and asthmatics +CS. Furthermore, in paired comparisons of asthmatics -CS and +CS, inhaled corticosteroids resulted in normalization of bronchial epithelial Cu,Zn-SOD specific activity. These findings suggest loss of Cu,Zn-SOD activity in asthma is related to inflammation, perhaps through oxidant inactivation of Cu,Zn-SOD protein.



Asthma but not smoking-related airflow limitation is associated with a high fat diet in men: Results from the population study 'Men born in 1914'

Monaldi Archives for Chest Disease (Italy), 1996, 51/1 (16-21)

The purpose of this study was to investigate whether there is an association between asthma and the intake of food with pro-oxidant or antioxidant activity (fat, alcohol, iron, zinc, and vitamins A and C), and to analyse whether any such association is specific to asthma or is found in airflow limitation in general. This study deals with 478 men, who were randomly selected from all the men born in Malmo in 1914. They were investigated using spirometry and their medical, occupational and dietary history was recorded in 1982-1983, at the age of 68 yrs, as part of the cohort study 'Men born in 1914'. Asthma was defined as a past or present physician's or nurse's diagnosis of asthma and airflow limitation was defined as a forced expiratory volume in one second/vital capacity ratio (FEV1/VC) of less than 70%, The relative risk of having asthma or airflow limitation as related to dietary intake at the age of 68 yrs was analysed after adjustments for smoking history and body mass index. Asthma was reported in 21 men and was not related to smoking history. Asthma was more common in men with a high fat intake (relative risk of asthma 1.74 for a 10% increase in fat intake, 95% confidence interval for the relative risk 1.13-2.68). The consumption of alcohol was higher for current smelters than ex-smelters and nonsmokers, and the intake of carbohydrates, vitamin C and iron was lower. Airflow limitation without asthma was present in 156 men and was related to smelting but not to dietary intake. Men with asthma had a significantly higher intake of fat than men without asthma. This difference appeared to be specific to asthma and was not found in airflow limitation in general.



Nutrient intake of patients with rheumatoid arthritis is deficient in pyridoxine, zinc, copper, and magnesium

Journal of Rheumatology (Canada), 1996, 23/6 (990-994)

Objective. To determine nutrient intake of patients with active rheumatoid arthritis and compare it with the typical American diet (TAD) and the recommended dietary allowance (RDA). Methods. 41 patients with active RA recorded a detailed dietary history. Information collected was analyzed for nutrient intake of energy, fats, protein, carbohydrate, vitamins and minerals, which were then statistically compared with the TAD and the RDA. Results. Both men and women ingested significantly less energy from carbohydrates (women 47.4% (6.4) vs 55% RDA, p = 0.0001; men = 48.9% (7.4), p = 0.025) and more energy from fat (women = 36.8% (4.5) vs 30% RDA. p = 0.001 and men = 35.2% (5.9) p = 0.02). Women ingested significantly more saturated and mono-unsaturated fat than the RDA (p = 0.02 and p = 0.04 respectively) while men ingested significantly less polyunsaturated fat (PUFA)(p = 0.0001). Both groups took in less fiber (p = 0.0001). Deficient dietary intake of pyridoxine was observed vs the RDA for both sexes (men and women p = 0.0001). Deficient folate intake was seen vs the TAD for men (p = 0.02) with a deficient trend in women (p = 0.06). Zinc and magnesium intake was deficient vs the RDA in both sexes (p values less than or equal to 0.001) and copper was deficient vs the TAD in both sexes (p = 0.004 women and p = 0.02 men). Conclusion. Patients with RA ingest too much total fat and too little PUFA and fiber. Their diets are deficient in pyridoxine, zinc and magnesium vs the RDA and copper and folate vs the TAD. These observations, also documented in previous studies, suggest that routine dietary supplementation with multivitamins and trace elements is appropriate in this population.



Trace elements in prognosis of myocardial infarction and sudden coronary death

Journal of Trace Elements in Experimental Medicine (USA), 1996, 9/2 (57-62)

Ca, Cu, Mg, Mn, and Zn concentrates were measured in plasma, RBC, and hair of 350 men aged 40-59 years with myocardial infarction (MI) and/or who died from sudden cardiac death (SCD), as compared with normal controls. Analyses were done by flame atomic absorption spectrophotometry. Cu in plasma of MI patients was significantly higher than the controls'. Plasma Mn was significantly lower in SCD than in MI subjects. No other consistent and significant changes were observed. Past and present evidence indicates that high plasma Cu levels may be associated with heart failure and rhythm disorders. The low plasma Mn levels may be an indicator of decreased parasympathetic tonus thus favouring myocardial desynchronization and A-V block. Cu inhibits phosphodiesterase activity and Mn inhibits andenylate cyclase activity thus exerting an influence on the contractility of cardiomyocites and of smooth muscle cells in coronary arteries. Cu and Mn analyses may thus have a prognostic significance for MI and SCD.



The biological significance of zinc

ANAESTHESIST (BERL.) (GERMANY, WEST), 1975, 24/8 (329-342)

Zinc takes part in the catalytic function of many metalloenzymes. In others it plays a role in conformational stability. In zinc deficient animals protein synthesis is disturbed. Conversely zinc metabolism is influenced by protein deficiency. Zinc takes part in drug metabolism, in mobilizing vitamin A from the liver, and in a system defending the organism against free radical damage. Zinc distribution in the organism is influenced by steroid hormones and leucocytic endogenous mediators. Of the intracellular zinc only a small part is bound to metalloenzymes, most being coordinated to binding sites of nonspecific proteins. Thus the organism defends itself against conformational changes of irritable enzymes which may bind excess zinc to side chains. Zinc can protect the organism against cadmium toxicity. In the serum the smaller part of zinc is firmly bound to several specific proteins, the majority being loosely bound to albumin. Some aspects of human zinc metabolism in health and disease are reviewed. Zinc deficiency in man is rare. In Iran and Egypt a syndrome of iron and zinc deficiency associated with anaemia, hepatosplenomegaly, dwarfism, and hypogonadism is known. In wound healing and tissue repair substitution of zinc is beneficial only if a zinc deficiency exists. For purposes of long term parenteral nutrition zinc should be added to the different infusion solutions.



[Deficiency of certain trace elements in children with hyperactivity]

Psychiatr Pol (POLAND) May-Jun 1994, 28 (3) p345-53

The magnesium, zinc, copper, iron and calcium level of plasma, erythrocytes, urine and hair in 50 children aged from 4 to 13 years with hyperactivity, were examined by AAS. The average concentration of all trace elements was lower compared with the control group-healthy children from Szczecin. The highest deficit was noted in hair. Our results show that it is necessary to supplement trace elements in children with hyperactivity.



Antioxidant status of hypercholesterolemic patients treated with LDL apheresis

Cardiovascular Drugs and Therapy (USA), 1996, 10/5 (567-571)

Oxidation of low density lipoprotein is involved in the pathogenesis of atherosclerosis. Epidemiological studies suggest a negative correlation between the occurrence of cardiovascular diseases and blood concentrations of lipophilic antioxidants such as vitamins A and E and beta-carotene. Trace elements, such zymes glutathione peroxidase and superoxide dismutase. The aim of this study was to determine the antioxidant and trace element status of patients with severe hypercholesterolemia who had been treated with dextran-sulphate low-density lipoprotein apheresis in comparison with two control populations, normocholesterolemic subjects and untreated hypercholesterolemic patients. Our results showed that, patients treated with LDL apheresis, compared with normocholesteromic subjects, were not deficient in vitamin E, beta-carotene, and copper, but had low plasma levels of selenium, zinc, and vitamin A. The low selenium and vitamin A levels were due to the LDL apheresis treatment, and the hypercholesterolemia might have provoked the low plasma levels of zinc.This study pointed out the potential benefits of supplemental selenium, zinc, and vitamin A in patients being treated with LDL apheresis.



The role of free radicals in disease

Australian and New Zealand Journal of Ophthalmology (Australia), 1995, 23/1

Evidence is accumulating that most of the degenerative diseases that afflict humanity have their origin in deleterious free radical reactions. These diseases include atherosclerosis, cancer, inflammatory joint disease, asthma, diabetes, senile dementia and degenerative eye disease. The process of biological ageing might also have a free radical basis. Most free radical damage to cells involves oxygen free radicals or, more generally, activated oxygen species (AOS) which include non-radical species such as singlet oxygen and hydrogen peroxide as well as free radicals. The AOS can damage genetic material, cause lipid peroxidation in cell membranes, and inactivate membrane-bound enzymes. Humans are well endowed with antioxidant defences against AOS; these antioxidants, or free radical scavengers, include ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), beta-carotene, coenzyme Q10, enzymes such as catalase and superoxide dismutase, and trace elements including selenium and zinc. The eye is an organ with intense AOS activity, and it requires high levels of antioxidants to protect its unsaturated fatty acids. The human species is not genetically adapted to survive past middle age, and it appears that antioxidant supplementation of our diet is needed to ensure a more healthy elderly population.



Aluminum, iron, and zinc ions promote aggregation of physiological concentrations of beta-amyloid peptide

Mantyh P.W.; Ghilardi J.R.; Rogers S.; DeMaster E.; Allen C.J.; Stimson E.R.; Maggio J.E.

Molecular Neurobiology Laboratory, Veterans Administration Medical Ctr., Minneapolis, MN 55417 USA

J. NEUROCHEM. (USA), 1993, 61/3 (1171-1174)

A major pathological feature of Alzheimer's disease (AD) is the presence of a high density of amyloid plaques in the brain tissue of patients. The plaques are predominantly composed of human beta-amyloid peptide betaA4, a 40- mer whose neurotoxicity is related to its aggregation. Certain metals have been proposed as risk factors for AD, but the mechanism by which the metals may exert their effects is unclear. Radioiodinated human betaA4 has been used to assess the effects of various metals on the aggregation of the peptide in dilute solution (10-10 M). In physiological buffers, 10-3 M calcium, cobalt, copper, manganese, magnesium, sodium, or potassium had no effect on the rate of betaA4 aggregation. In sharp contrast, aluminum, iron, and zinc under the same conditions strongly promoted aggregation (rate enhancement of 100- 1,000-fold). The aggregation of betaA4 induced by aluminum and iron is distinguishable from that induced by zinc in terms or rate, extent, pH and temperature dependence. These results suggest that high concentrations of certain metals may play a role in the pathogenesis of AD by promoting aggregation of betaA4.



Alzheimers disease/alcohol dementia: Association with zincdeficiency and cerebral vitamin B12 deficiency

J. ORTHOMOL. PSYCHIATRY (CANADA), 1984, 13/2 (97-104)

It is demonstrated that patients with senile dementia Alzheimer's type (SDAT) and alcohol related brain damage (AD) show a significant increase in ratio se-Cu/se-Zn when compared with patients with multi-infarct dementia (MID) and when compared with a matched control group. This is regarded as an indicator of zinc deficiency and relative copper toxicity in SDAT and AD, not in MID. In the same groups with SDAT and AD a high incidence of pathologically low levels of vitamin B12 in cerebrospinal fluid (CSF) was found, despite normal serum B12 levels. In MID the normal serum B12 corresponded with a normal CSF B12. This indicates abnormal function of the choroid plexus and possibly of the bloodbrain barrier in SDAT and AD, not in MID. Discussed is the possibility that in a large sub-group of SDAT and AD the clinical, neurochemical and neuropathological data can be explained by the hypothesis that the combination of zinc deficiency and copper toxicity results in limbic disinhibition and defective central noradrenergic neurotransmission. The neuroendocrine effects of the limbic disinhibition and the impaired regulation of the cerebral micro-circulation by the defective noradrenergic system will result in dysfunction of the blood-brain barrier and the choroid plexus, resulting as has been demonstrated in a CSF B12 deficiency. Such an effect is strongly potentiated by a co-existent depression. Due to the reduced plasticity of the aging brain the presentation of this organic affective syndrome and/or depression is under a 'dementia' disguise, facilitated by organic cerebral changes caused primarily by zinc deficiency and copper toxicity, secondarily by the cerebral B12 deficiency. Early recognition and adequate treatment with nutritional supplementation can possibly prevent irreversible damage in subgroups of SDAT and AD. Primary prevention by nutritional strategies can be a realistic perspective. The need for further research into this challenging hypothesis is stressed.



Rationales for micronutrient supplementation in diabetes.

Med Hypotheses (ENGLAND) Feb 1984, 13 (2) p139-51

Available evidence--some well-documented, some only preliminary--suggests that properly-designed nutritional insurance supplementation may have particular value in diabetes. Comprehensive micronutrient supplementation providing ample doses of antioxidants, yeast-chromium, magnesium, zinc, pyridoxine, gamma-linolenic acid, and carnitine, may aid glucose tolerance, stimulate immune defenses, and promote wound healing, while reducing the risk and severity of some of the secondary complications of diabetes. (125 Refs.)

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