Parenteral Zinc Research Articles

Zinc supplementation in preterm infants and growth indicators in a developing country

Background Zinc is one of the micronutrients that is found deficient in preterm infants. To date, no parenteral zinc supplements are available in Indonesia and there is no recommendation established for routine zinc supplementation in preterm infants.
 Objective To evaluate the impact of zinc supplementation on growth indicators and morbidity in preterm infants.
 Methods This double-blind, randomized controlled trial included preterm infants aged 28-32 weeks who were assigned to one of two groups: the first group received a 10 mg zinc supplementation, while the second (control) group received a placebo. At discharge or at a maximum of 40 weeks post-menstrual age (PMA, calculated from the first day of the mother's last menstrual period), the following were evaluated : growth indicators (weight, length, and head circumference), serum zinc level, zinc supplementation side effects, and morbidity rate (intraventricular hemorrhage/IVH, necrotizing enterocolitis/NEC, btonchopulmonary dysplasia/BPD). Data were analyzed with independent T-test using SPSS version 22 software.
 Results Seventy-eight subjects were assigned to the zinc supplementation group and 76 subjects were assigned to the placebo group. Serum zinc level and mean body weight increment were significantly higher in the zinc group compared to the placebo group (P=0.00 and P=0.02, respectively). There were no significant differences between groups in mean body length or head circumference increment, nor in morbidity rate.
 Conclusion Preterm infants who received zinc supplementation have higher serum zinc level and mean body weight increment compared to the placebo group. No side effects are observed to have been caused by zinc supplementation.
 
 

Exogenous copper exposure causing clinical wilson disease in a patient with copper deficiency

BackgroundHuman Swayback is a disease characterized by acquired copper deficiency which primarily manifests as myeloneuropathy. Common causes include malabsorptive disorders, gastric surgery, total parenteral nutrition and excessive zinc intake. In contrast, copper supplementation should be closely monitored as excessive doses can lead to acute intoxication and in chronic cases, cirrhosis. Copper derangements are rare, however it is important to consider them due to potential severe complications.Case presentationWe present a middle-aged man who had been previously diagnosed with Human Swayback after presenting with various neurological symptoms. The patient was subsequently placed on copper supplementation. A decade later, he was referred to our hospital for liver transplant evaluation due to new diagnosis of decompensated end-stage liver disease after an abdominal surgery. His initial workup was suggestive of Wilson disease—subsequent ATP7B gene was negative. Ultimately, the patient underwent liver transplantation; liver explant was significant for a copper dry weight concentration of 5436 mcg/g.ConclusionsHuman Swayback is a very rare copper-related disease which deserves awareness due to its potential irreversible health effects in the human body. Additionally, in patients who require copper supplementation, serial levels should be monitored to ensure adequate copper levels.

Энтеропатический акродерматит у детей

Enteropathic acrodermatitis is a rare hereditary form of zinc deficiency, characterized by periorial and acral dermatitis, alopecia and diarrhea. Refers to congenital disorders of zinc metabolism, inherited as an autosomal recessive disease resulting from mutations in the gene for the zinc transporter SLC39A4. The prevalence ranges from 1 to 9:1,000,000, with an overall incidence of 1:500,000 newborns. The disease usually manifests itself in infancy, within a few weeks of stopping breastfeeding and switching the baby to a cow's milk-based formula, or in the first days of life if artificially fed from birth. The classical clinical manifestations of acrodermatitis enteropathic are characterized by the triad: acral and periofital dermatitis, alopecia and diarrhea, but all three signs together occur only in 20% of cases. Diarrhea may develop concurrently with skin symptoms, may precede or occur later. Characteristic signs of skin lesions include sharply demarcated, dry, scaly erythematous plaques or edematous foci with vesicles and pustules on the skin of the elbow and knee joints, distal extremities, genitals, in the inguinal folds, which are usually symmetrically distributed, have sharp boundaries and irregular outlines. The course of the skin syndrome is long, as it progresses, non-healing erosive and ulcerative areas appear. Plasma zinc deficiency is the gold standard for diagnosis. Most infants with AE have low plasma zinc concentrations (<500 mcg/L or <50 mcg/dl), but a level of less than 70 mcg/L on an empty stomach or less than 65 mcg/dl in older non-dieting children is considered diagnostically significant. Treatment for this disease usually includes enteral or parenteral zinc administration, at a dose of 1-3 mg/kg/day. for elemental zinc. A clinical response is observed within 5–10 days. Supportive zinc therapy is necessary throughout the patient's life, although periods of remission have been reported. Topical therapy is also used: Dexpanthenol in the form of a cream, applied 3 times a day in the area of dermatitis, can enhance re-epithelialization. There is no significant evidence of improvement with topical zinc application. No activity restrictions are required for patients with acrodermatitis enteropathic. Key words: zinc deficiency, enteropathic acrodermatitis, children

Parenteral Zinc Intake in Newborns With Jejunostomy or Ileostomy: Results of a Monocentric Cohort Study.

The aim of the study was to assess zinc status of newborns with parenteral nutrition with or without a small bowel stoma, to determine the incidence of zinc deficit, and to determine the clinical factors associated with plasma zinc levels. Monocentric cohort study including all liveborn infants receiving zinc parenteral intake at 500 μg · kg · day and who benefited from at least 1 plasma zinc assessment during hospitalization. Sixty-eight dosages of zinc were performed in 50 newborns, divided into 3 groups (no stoma = 26, jejunostomy = 11, ileostomy = 13). Thirty-seven of the 50 infants were born preterm. The mean ± standard deviation plasma zinc was 14.9 ± 4.3 μmol/L and was similar among the 3 groups. Sixty-four percent, 3%, and 34% of zinc values were within, below, and above the normal range, respectively. In infants with jejunostomy, only 1 plasma zinc value (5%) was below the reference range. Plasma zinc levels were negatively correlated with stoma output (r = -0.449; P = 0.013). In contrast to patients with limited intestinal losses (ie, no stoma and ileostomy groups) no association between zinc levels and postmenstrual age was observed in infants with a jejunostomy suggesting that 500 μg · kg · day was adequate not only in preterm infants but also in term infants with a jejunostomy. Plasma zinc levels decrease significantly with the increase of stoma output volume of newborns with small bowel stoma. Zinc deficit was prevented in newborns with a small bowel stoma receiving of 500 μg · kg · day of parenteral zinc.

An extracellular histidine-containing motif in the zinc transporter ZIP4 plays a role in zinc sensing and zinc-induced endocytosis in mammalian cells

Zinc is an essential trace element that serves as a cofactor for enzymes in critical biochemical processes and also plays a structural role in numerous proteins. Zinc transporter ZIP4 (ZIP4) is a zinc importer required for dietary zinc uptake in the intestine and other cell types. Studies in cultured cells have reported that zinc stimulates the endocytosis of plasma membrane-localized ZIP4 protein, resulting in reduced cellular zinc uptake. Thus, zinc-regulated trafficking of ZIP4 is a key means for regulating cellular zinc homeostasis, but the underlying mechanisms are not well understood. In this study, we used mutational analysis, immunoblotting, HEK293 cells, and immunofluorescence microscopy to identify a histidine-containing motif (398HTH) in the first extracellular loop that is required for high sensitivity to low zinc concentrations in a zinc-induced endocytic response of mouse ZIP4 (mZIP4). Moreover, using synthetic peptides with selective substitutions and truncated mZIP4 variants, we provide evidence that histidine residues in this motif coordinate a zinc ion in mZIP4 homodimers at the plasma membrane. These findings suggest that 398HTH is an important zinc-sensing motif for eliciting high-affinity zinc-stimulated endocytosis of mZIP4 and provide insight into cellular mechanisms for regulating cellular zinc homeostasis in mammalian cells.

Trace Element Supplementation Following Severe Burn Injury: A Systematic Review and Meta-Analysis.

Trace elements have an important physiological role after severe burn injury with patients routinely receiving supplementation. Although commonly prescribed after burn injury, variation exists among supplement composition, frequency, and the dosage administered. This review aims to assess the effectiveness of trace element supplementation on clinically meaningful outcomes in patients who have sustained a severe burn injury. Supplementation of selenium, copper and zinc, either alone or combined, compared with placebo or standard treatment were eligible for inclusion. Predetermined primary outcome measures were mortality, length of stay, rate of wound healing, and complications. A comprehensive search strategy was undertaken. Methodological quality of eligible studies was appraised and relevant data extracted for meta-analysis. Eight studies met eligibility criteria for the review; four randomized controlled trials and four nonrandomized experimental trials, including a total of 398 participants with an age range of 6 to 67 years. Parenteral supplementation of combined trace elements was associated with a significant decrease in infectious episodes (weighted mean difference: -1.25 episodes, 95% confidence intervals: -1.70, -0.80; P < .00001). The results of this review indicate that the use of parentally administered combined trace elements after burn injury confer positive effects in decreasing infectious complications. Combined parenteral trace element supplementation and combined oral and parenteral zinc supplementation have potentially clinically significant findings on reducing length of stay. Oral zinc supplementation shows possible beneficial effects on mortality. Definitive studies are required to accurately define optimal trace element supplementation regimens, dosages, and routes after burn injury.

Zinc in traumatic brain injury

In light of the recent recognition that even mild forms of traumatic brain injury (TBI) can lead to long-term cognitive and behavioral deficits, this review examines recent data on the neuroprotective and neurotoxic roles of zinc after brain injury. Data show that treatment using dietary and parenteral zinc supplementation can reduce TBI-associated depression and improve cognitive function, specifically spatial learning and memory. However, excessive release of free zinc, particularly in the hippocampus associated with acute injury, can lead to increases in protein ubiquitination and neuronal death. This work shows the need for future research to clarify the potentially contradictory roles of zinc in the hippocampus and define the clinical use of zinc as a treatment following brain injury in humans. This is particularly important given the finding that zinc may reduce TBI-associated depression, a common and difficult outcome to treat in all forms of TBI.

Zinc, Copper, and Selenium Tissue Levels and Their Relation to Subcutaneous Abscess, Minor Surgery, and Wound Healing in Humans

Trace element involvement in wounds left to heal by secondary intention needs clarification. We have previously reported faster healing of wounds following acute surgery compared with elective excision of pilonidal sinus disease. The effect of topical zinc on the closure of the excisional wounds was mediocre compared with placebo. In contrast, parenteral zinc, copper, and selenium combined appear effective for wound healing in humans. We have investigated zinc, copper, and selenium with respect to (a) impact of acute versus chronic pilonidal sinus and (b) regional concentrations within granulating wounds treated topically with placebo or zinc in 42 (33 males) pilonidal disease patients. Baseline serum and skin concentrations of copper correlated (r S = 0.351, p = 0.033, n = 37), but not of zinc or selenium. Patients with abscesses had elevated serum C-reactive protein (CRP) and copper levels (+29%; p < 0.001) compared with the elective patients consistent with the strong correlation between serum copper and CRP (r S = 0.715, p < 0.0005, n = 41). Seven days after elective surgery, serum CRP and copper levels were elevated (p = 0.010) versus preoperative values. The copper concentration in wound edges was higher than in periwound skin (p < 0.0005) and wound base (p = 0.010). Selenium levels were increased in wound edge compared to wound base (p = 0.003). Topical zinc oxide treatment doubled (p < 0.050) zinc concentrations in the three tissue localizations without concomitant significant changes of copper or selenium levels. In conclusion, copper and selenium are mobilized to injured sites possibly to enhance host defense and early wound healing mechanisms that are complementary to the necessity of zinc for matrix metalloproteinase activity.

Tissue Mineral Concentrations Are Profoundly Altered in Neonatal Piglets Fed Identical Diets via Gastric, Central Venous, or Portal Venous Routes

Because gut absorption and liver sequestration are major mechanisms of mineral homeostasis, intestinal and hepatic bypass with parenteral feeding can lead to mineral toxicities. We employed a piglet model with multiple feeding routes to identify target organs susceptible to abnormal accumulation of minerals and to determine the importance of intestinal or hepatic metabolism. Fifteen 2- to 4-day-old piglets were fed identical complete elemental diets continuously for 8 days via central venous (intravenous [IV]), gastric (intragastric [IG]), or portal (intraportal [IP]) catheters. Concentrations of calcium, phosphorus, magnesium, zinc, copper, iron, manganese, sodium, potassium, and chloride were measured in small intestinal mucosa, liver, kidney, and femur. Compared with IG-fed piglets, mineral sequestration patterns in IV- and IP-fed piglets can be attributed to bypass of intestinal absorption inefficiencies, with moderate accumulations of minerals in tissues involved in mineral homeostasis. However, differences between IP and IV feeding were notable for iron, manganese, and copper, suggesting first-pass hepatic metabolism is key to homeostasis of these minerals. Moreover, manganese and copper sequestration patterns reflected that for zinc, suggesting induction of metallothionein by parenteral zinc could interfere with metabolism of other minerals. We conclude that parenteral delivery of minerals to neonates needs to consider not only absorption efficiency but also mineral interactions and potentially toxic accumulation in target tissues, with particular concern for iron, copper, and zinc.

Dosing and Monitoring of Trace Elements in Long‐Term Home Parenteral Nutrition Patients

Trace elements (TEs) dosing and monitoring in home parenteral nutrition (PN) patients vary with their underlying conditions. This retrospective observational study evaluated parenteral TE dosing, serum TE concentrations and monitoring, and dose-concentration relationships between TE doses and serum TE concentrations in 26 adult and adolescent home PN patients. There was a total of 40,493 PN days. Average parenteral zinc doses of 9.1 mg/d and 7.6 mg/d resulted in the majority of serum zinc concentrations (90%) within normal range in patients with and without short bowel syndrome (SBS), respectively. Selenium at about 70 mcg/d resulted in about 60% of serum selenium concentrations within normal range, with 38% of values below normal in patients with and without SBS alike. Copper at 1 mg/d resulted in 22.5% of serum copper concentrations above the normal range. The majority of serum manganese (94.6%) and chromium (96%) concentrations were elevated. Serum TE concentrations were infrequently monitored. Significant relationships existed between doses and serum concentrations for zinc (P < .0001), manganese (P = .012), and chromium (P < .0001) but not for selenium or copper. TE doses in home PN should be individualized and adjusted based on regular monitoring of TE status. In long-term home PN patients, higher zinc and selenium doses may be necessary to maintain their normal serum concentrations. Lower copper doses and restrictions of manganese and chromium supplementation may be needed to avoid their accumulation. Relationships between TE doses and serum TE concentrations vary for each TE and underlying clinical conditions.

Zinc: An Essential Trace Element for Parenteral Nutrition

Zinc is an essential trace element for human nutrition that is an integral part of many enzyme systems, including DNA polymerase complex. Zinc deficiency has been associated with stunting of growth and sexual immaturity. In children, deficiency causes a fatal condition called acrodermatitis enteropathica. The same syndrome has been observed in patients on total parenteral nutrition (TPN) who do not receive zinc. In TPN the requirements have been estimated by balance studies to be 3 mg/d in patients without gastrointestinal losses and a mean of 12 mg/d in patients with diarrhea and fistula losses.

Effect of parenteral zinc sulfate on colon anastomosis repair in the rat

To prevent colonic anastomotic dehiscence, pharmaceutical interventions should inhibit degradation of existing submucosal collagen fibers and accelerate the synthesis of new collagen molecules. Zinc has multiple functions in collagen metabolism and was recently found beneficial in colonic anastomosis repair. We have investigated the effect of daily intraperitoneal zinc (2 mg/kg) injections on the development of the biomechanical integrity of left colon anastomoses. Sixty Sprague-Dawley male rats (median 245 g) were allocated to treatment with zinc sulfate in saline (n = 30) or with saline alone (n = 30) starting 1 h before the anastomoses were made. Serum zinc levels and anastomotic breaking strength were determined on postoperative days 3 (n = 30) and 7 (n = 30). The initial breaking strength or suture-binding capacity was determined in additional ten non-treated animals (277 g). The breaking strength of the anastomoses decreased in the two groups combined (n = 30) by 50% (p < 0.001) on day 3 but was regained by postoperative day 7 compared with the initial anastomotic biomechanical strength. Serum zinc levels also increased from day 3 to day 7 in both intervention groups and correlated significantly with breaking strength (r = 0.57, p < 0.001). Although the median serum zinc level was 14% higher (p < 0.01) on day 7 in zinc-treated than in saline-treated animals, the breaking strength did not differ significantly between zinc-treated and saline-treated rats on either day 3 (p = 0.95) or day 7 (p = 0.70). In contrast to previous report in rabbits, we failed to demonstrate the beneficial effects of parenteral zinc supplementation on colon anastomosis repair in a rat model.

Copper deficiency myelopathy induced by repetitive parenteral zinc supplementation during chronic hemodialysis

Copper deficiency myelopathy induced by repetitive parenteral zinc supplementation during chronic hemodialysis

Wound problems due to zinc deficiency

Zinc deficiency, though uncommon, can occasionally present in current medical practice. A 4.5-year-old boy with previous gastrointestinal surgery presented with diarrhoea, disinterest and dermatitis affecting the face and perineum. The clinical diagnosis was confirmed by the presence of a low serum zinc level. Administration of parenteral zinc led to rapid improvement in diarrhoea, demeanor and dermatitis. Further surgery was then undertaken, surgery had been postponed until normalisation of zinc levels due the association between zinc deficiency and poor postoperative wound healing.

Zinc-responsive dermatosis in dogs: 41 cases and literature review.

Forty-one cases of zinc-responsive dermatosis in the dog are described. The Siberian husky was the predominant breed affected. Periocular crusts were the most common clinical sign and parakeratosis was noted in the skin biopsy specimens of all dogs. Treatment with oral zinc ameliorated the clinical signs in most dogs, but cases necessitating other treatments such as parenteral zinc or retinoids are reported. The authors recommend a starting dose of 2-3 mg kg-1 elemental zinc per day in the treatment of this disorder.

Chromium and zinc concentrations in pediatric patients receiving long-term parenteral nutrition.

Serum, urine, and parenteral nutrition (PN) chromium and zinc concentrations in pediatric patients receiving long-term PN were studied. Serum, urine, and PN chromium and zinc concentrations were measured at baseline and four to six months later in four infants (less than 1 year old) and seven children (1-12 years old) receiving long-term PN. In the children, serum, urine, and PN solution zinc concentrations were measured monthly after the amino acid product was changed from a standard to a pediatric product with monthly dosages of 0, 20, 30, and 40 mg of cysteine hydrochloride per gram of amino acids. The mean +/- S.D. baseline serum chromium concentration was 4.9+/-1.9 microg/L (normal value, <0.3 microg/L); the urine chromium concentration ranged from 3.4 to 32.2 microg/L. The mean +/- S.D. prescribed chromium dosage was 0.18+/-0.05 microg/kg/day, and the dosage delivered in PN solutions was 0.41+/-0.23 microg/ kg/day. At baseline, the mean +/- S.D. serum zinc concentration was 1383+/-472 microg/L (normal range, 430 to 940 microg/L), and the prescribed and delivered zinc dosages were 177+/-10 and 238+/-145 microg/kg/ day, respectively. With 20, 30, and 40 mg of cysteine per gram of amino acids, the mean +/- S.D. serum zinc concentration was 1728+/-782, 1664+/-349, and 1685+/-268 microg/L, respectively, and the actual zinc dosages delivered were 209+/-10, 270+/-148, and 322+/-194 microg/kg/day, respectively. Serum and urine chromium concentrations were abnormally high in infants and children receiving PN solutions supplemented with normal doses of these trace elements; an escalating dosage of cysteine in the children tended to increase serum and urine zinc concentrations.

The Importance of Total Parenteral Nutrition-Associated Tissue Zinc Distribution in Wound Healing

The Importance of Total Parenteral Nutrition-Associated Tissue Zinc Distribution in Wound Healing

The importance of total parenteral nutrition-associated tissue zinc distribution in wound healing.

It is well known that zinc (Zn), an essential trace element, plays a role in wound healing. Although the importance of Zn supplementation in total parenteral nutrition (TPN) has been recognized, the difference in tissue Zn distribution induced by TPN and whether this difference influences local wound healing remains uncertain. Thus, we conducted a study using 30 Sprague-Dawley rats to investigate the influence of TPN-induced changes in tissue Zn distribution on wound healing at sites of intestinal anastomosis, muscle, and skin sutures. In the ordinary diet group, no significant differences were observed between subgroups with and without supplemental Zn in tissue Zn distribution or in the healing of intestinal, muscular, and cutaneous wounds. In the subgroup given a low-protein diet without supplemental Zn, a gross change in tissue Zn distribution was noted to occur with a concomitant marked decrease in Zn concentration and the tensile strength of wounded skin. These results indicate an association between wound healing and Zn concentration in the respective tissues in TPN-induced Zn deficiency with alternations in tissue Zn distribution. They also provide evidence of the local action of Zn in wound healing.

Parenteral Zinc Supplementation in Adult Humans during the Acute Phase Response Increases the Febrile Response , ,

The acute phase response (APR) that follows injury or infection is characterized by a decrease in serum zinc concentrations, which we hypothesized benefits the host. Additionally, we proposed that preventing this decline by supplementing zinc would result in an exaggerated APR as indicated by elevated temperatures, increased serum cytokine concentrations, interleukin 6 and the acute phase protein (ceruloplasmin). A prospective, randomized, double-blinded, clinical trial was conducted. Patients on home parenteral nutrition with a diagnosis of catheter sepsis and patients with a diagnosis of pancreatitis, also on total parenteral nutrition (TPN), were recruited for the study. Following enrollment, block randomization was used to assign patients to receive 0 mg (n = 23) or 30 mg (n = 21) of zinc per day for the first 3 d of TPN. Blood samples for measurement of serum zinc, copper, ceruloplasmin and interleukin-6 were obtained upon enrollment and on d 1 through 3 of TPN. The highest temperatures reported on these days in the medical record were also recorded. Repeated measures ANOVA was used to determine differences in the primary outcome variables over time. No significant differences between groups were observed in serum interleukin-6 or ceruloplasmin concentrations. A significantly higher (P = 0.035) temperature was observed in the zinc-supplemented group compared with the control group on d 3 of parenteral nutrition. We conclude that parenteral zinc supplementation in patients experiencing a mild APR resulted in an exaggerated APR as evidenced by a significantly higher febrile response.

Zinc-induced metallothionein and copper metabolism in intestinal mucosa, liver, and kidney of rats

Large doses of parenteral zinc (Zn) and/or the feeding of high Zn diets to animals or humans for long periods affects copper (Cu) metabolism. Previous work suggests that Zn-induced metallothionein (MT) in intestinal epithelial cells binds Cu and inhibits its absorption. This study was designed to determine the effects of treating rats with high dietary or high parenteral Zn on Cu metabolism and its relationship to MT in the intestinal epithelium, liver and kidney. Six-week-old male rats were fed for one week a control diet containing 42 mg Zn and 6 mg Cu/kg. They were then divided into three groups. One group continued to receive the control diet while another received a similar diet containing 560 mg Zn/kg. A third group, fed the control diet, received a subcutaneous dose of 90 mg Zn/kg body weight every 2–3 days for the duration of the experiment. Rats from each group were killed on days 7 and 14. Low Cu status in Zn-treated rats was indicated by lower than normal serum Cu concentration, serum ceruloplasmin activity, low liver and kidney Cu concentrations and low cytochrome C oxidase activity. None of these changes, however, were related to an increase in Cu as a result of Zn-induced MT in the intestinal epithelial cell. Instead, as the MT concentrations rose, Cu concentration decreased. This study suggests that the effects of high Zn treatment on Cu status are not the result of the long-held theory that Zn-induced intestinal MT sequesters Cu and prevents its passage to the circulation. Instead, it may be caused by a direct effect of high lumenal Zn concentrations on Cu transport into the epithelial cell.