Internal References:
Zinc
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Hunt JR Matthys LA Johnson LK. Am J Clin Nutr
(1998 Mar) 67(3):421-30 Zinc absorption, mineral balance, and blood
lipid concentrations were measured in 21 women aged
20 to 42 years consuming controlled lacto
ovovegetarian and nonvegetarians diets for 8 weeks
each, in a crossover design. The lacto
ovovegetarian and nonvegetarians diets,
respectively, provided 973 and 995 mg calcium, 1.8
and 1.3 mg copper, 367 and 260 mg magnesium, 5.9
and 2.5 mg manganese, 1,457 and 1,667 mg
phosphorus, 9.1 and 11.1 mg zinc, and (by
calculation) 40 and 16 grams dietary fiber, 2.5 and
0.8 mmol phytic acid, molar ratios of phytate to
zinc of 14 and 5, and millimolar ratios of (phytate
x calcium) to zinc of 344 and 111. Dietary zinc
absorption was measured by extrinsic isotopic
labeling and whole-body counting. Plasma
cholesterol, cholesterol fractions, and
lipoproteins were reduced 7 to 12% with the lacto
ovovegetarian diet, consistent with predictions
based on dietary cholesterol and fat. Blood
pressure was unaffected. Calcium, copper, magnesium
and phosphorus balances were not different between
diets; manganese balance tended to be greater with
the lacto ovovegetarian diet (P < 0.07). The lacto
ovovegetarian diet was associated with a 21%
reduction in absorptive efficiency that, together
with a 14% reduction in dietary zinc, reduced the
amount of zinc absorbed by 35% (2.4 compared with
3.7 mg/d) and reduced plasma zinc by 5% within the
normal range. Zinc balance was maintained with both
diets. Although there is a greater risk of zinc
deficiency in persons consuming lacto ovovegetarian
compared with omnivorous diets, with inclusion of
whole grains and legumes zinc requirements can be
met and zinc balance maintained.
INDIAN J. ORTHOP. (INDIA), 1980, 14/1 (62-71) In the present experimental study, 36 rabbits
were subjected to fracture of the of the fibula and
were treated in 3 groups viz., Control group, Zinc
sulphate supplemented group and Zinc sulphate vit.
C. + Methandienone supplemented group. Each group
consisted of 12 rabbits. After roentgenological,
macroscopic and histological examination of healing
of fractures of weekly intervals, it was concluded
that the Zinc supplementation to an appreciable
extent enhanced the process of bone healing which
could be further hastened by addition of Vitamin C
and Dianabol. No significant toxic or side effect
of zinc supplementation was observed in any of the
rabbits. A clinical trial of the same drugs was
also conducted in patients with fractures of the
shaft of the femur.
Rev Esp Enferm Dig (SPAIN) Nov 1996, 88 (11)
p757-62 A multicentric double-blind trial comparing 600
mg/d of Zinc Acexamate (ACZ) and 40 mg/d of
Famotidine (FMT) in the short term treatment of
acute duodenal ulcer included 199 patients,
diagnosed by endoscopy. One-hundred and five
patients received ACZ and 94 FMT, during four
weeks. A clinical control took place at two weeks
and a second clinical and endoscopic control at the
end of the treatment (4 weeks). Complete
cicatrization of the ulcer was observed in 56.5% of
patients on ACZ and in 69.5% of patients of FMT (N.S.).
A reduction of more than 50% of the ulcer diameter
was recorded in 78.8% of the ACZ group and in 79.9%
of the FMT group. Alcohol and smoking did not
influence the results. Both treatments were equally
effective in the disappearance of symptoms. The
incidence of adverse reactions was very low in both
groups (< 5%) and no patient dropped from the trial
for this reason. In conclusion, a dosage of 600
mg/d of ACZ has ptors:
Biometals (ENGLAND) Oct 1996, 9 (4) p371-5 Exogenously administered zinc compounds have
been shown to possess anti-ulcer activity against a
wide variety of ulcerogenic agents, both in
laboratory animal models and in human peptic ulcer
disease. However, a strong possibility exists that
endogenous zinc may also play an important role
during noxious events by various mechanisms.
Therefore, the aim of this study was to focus on
the changes of endogenous zinc serum and tissue
concentrations in cysteamine-induced duodenal
lesions. We used atomic absorption
spectrophotometry to determine the tissue and serum
concentrations of zinc in normal (control) rats and
those with cysteamine-induced duodenal ulcers. The
results obtained in this study indicated that the
onset, development and spontaneous healing of ulcer
lesions were associated with certain shifts in zinc
serum and tissue concentrations. Prior to ulcer
formation, a significant increase was noted in
serum zinc values. With the onset of duodenal
lesions, zinc serum concentrations significantly
decreased, while there was a significant increase
in duodenal tissue concentrations when compared to
healthy control animals. Zinc tissue concentrations
decreased and returned to starting values by the
end of the first week of spontaneous healing. This
decrease in zinc tissue concentration corresponded
to the healing rate of the duodenal ulcers. Serum
zinc concentrations also returned to starting
values within the first week period. These
observations indicate and confirm that zinc could
play an important role in duodenal ulcer disease
and represent a natural defense system in the body.
British Journal of Dermatology (United Kingdom),
1997, 136/5 (783-785) Necrolytic migratory erythema (NME) is an
uncommon condition classically associated with high
plasma levels of circulating glucagon and a
glucagonoma. We report a patient with cirrhosis who
showed clinical and histological features of NME.
Investigation revealed normal glucagon levels
without evidence of glc supplementation resulted in
rapid and complete resolution of the eruption.
Asian Journal of Surgery (Hongkong), 1997, 20/1
(42-46) The role of mast cells in wound healing in a
racial group of Proto Malay people living in Timor,
Indonesia was studied. The relationship between
fine scar formation after cleft lip reconstruction
surgery, the growing evidence of micronutrient zinc
deficiency in the region and an unusual number of
mast cells distributed in the skin compared with a
racial group of Deutero Malay people living in
Malang, East Java, Indonesia was explored. It has
been suggested that a possible role of mast cells,
in a zinc deficient area, is that they accumulate
zinc to compensate for the deficiency and to
provide the necessary amount for better wound
healing. Further investigations are still under way
to give a more sound understanding of mast cells as
zinc carriers.
Biological Trace Element Research (USA), 1996,
54/2 (105-112) The element Zn is the metal component or
activator of many important enzymes. The tissue
concentrations and activities of Zn metalloenzymes
direct the rate of protein and nucleic acid
syntheses, thereby influencing tissue growth and
reparative processes. Most of the serum Zn is
normally bound to circulating proteins. Low serum
Zn concentrations might result from depletion of
Zn-binding proteins. Serum protein and Zn
concentrations have been reported to be depressed
in patients with acute and chronic diseases. We
compare the serum protein and Zn values of patients
with thoracic empyema (n = 20) with those of a
control group (n = 20). The values obtained in the
empyema group were significantly lower than those
in the control group before the study. Test group
administered 220 mg zinc sulfate (ZnSO4. 7H2O) over
20 d and there was a significant increase in the
values for serum protein and Zn after the oral
administration of the zinc sulfate.
Biological Trace Element Research (USA), 1996,
53/1-3 (19-25) For many years, zinc salts have been used both
topically and orally to treat minor burns and
abrasions as well as to enhance wound repair in man
and animals. In this study we describe the
protective effects of zinc against UV- induced
genotoxicity in vitro and against sunburn cell
formation in mouse skin in vivo. Cultured skin
cells from neonatal mice showed a dramatic increase
in the number of micronuclei as a result of UVA and
UVB irradiation. Inclusion of zinc at 5 microg/mL
in the medium significantly reduced the frequency
of micronuclei and of micronucleated cells. In
hairless mice, topical application of zinc chloride
for 5 consecutive days or a single application 2 h
prior to UV exposure reduced the number of sunburn
cells in the epidermis as did application of zinc 1
h after exposure. Application 2 h after irradiation
also tended to have a protective effect, although
there was a large variation between animals. It is
proposed that an influx of zinc can protect
epidermal cells against some of the more delayed
effects of UV-induced damage.
Turkish Journal of Gastroenterology (Turkey),
1996, 7/1 (72-81) Today adjuvant therapy using early postoperative
intraperitoneal chemotherapy, is particularly
appropriate treatment to prevent the local and
regional recurrence in resectable colon cancers.
Intraperitoneal 5-Fluorouracil (5-FU) is the most
preferable agent for this purpose. The aim of this
study is to determine the effect of Zn against the
inhibitory effect of 5-FU on the healing of colonic
anastomosis. In 5-FU treated group, average
bursting pressure (p:0.048) and hydroxyproline
levels were significantly decreased (p:0.015). In
only Zn treated group, average bursting pressure
was significantly increased (p:0.02) whereas
hydroxyproline levels showed no correlation with
the control group (p:0.560). In both 5-FU and Zn
treated groups average bursting pressure had
statistically significant correlation only with the
5-FU treated group (p:0.014). In this group
hydroxyproline levels were increased as well
(p:0.014). The histological observations showed
that 5-FU impaired the healing of colonic
anastomosis with the appearance of necrotic tissue
at the anastomosis region. However the 5-FU and Zn
groups appeared to be nearly completely
epithelialized and also the number of fibroblasts
were increased while necrotic ti much as in the
5-FU treated group. We conclude that Zn addition
modulates healing of colonic anastomosis by
counteracting the negative effect of 5-FU.
Advances in Therapy (USA), 1996, 13/2 (88-94) Zinc-saline wet dressings were compared to
normal-saline wet dressings for the management of
lower extremity ulcers in a pilot study of 28
elderly patients. Although both study groups were
comparable at baseline, the data suggest that the
use of zinc-saline wet dressings creates a wound
environment that is associated with trends toward
faster healing and enhanced rates of
epithelialization, as well as significantly more
efficient wound management than the normal-saline
controls. These data are presented in light of the
requirement for maintaining a moist, acidic
environment within a wound in order to permit the
best possible healing and remodeling.
European Journal of Clinical Nutrition (United
Kingdom), 1995, 49/4 (282-288) Design: Placebo for 3 months, followed by 30
mg/day zinc gluconate in identical capsules.
Setting: Diabetic out patients clinic at the
University Hospital, Grenoble. Subjects: Diabetic
patients cared for type I diabetes mellitus. 22
patients began the study, 4 dropped out. 10
patients suffered of an early retinopathy, 8
patients had no retinopathy. Interventions: In this
order: T0 biological measurements, 3 months placebo
treatment, T1 biological measurements, 3 months
zinc gluconate treatment, T2 biological
measurements. Plasma Zn, Cu, Se, thiobarbituric
acid reactants and antioxidant enzymes were
measured (plasma and red glutathione peroxidase
(Se-GPx), red cell superoxide dismutase
(Cu-Zn-SOD)). Results: Lower plasma zinc level in
the two groups. An increase in zinc level was
observed and was more important in diabetic
patients with no retinopathy (P = 0.05). The
thiobarbituric acid reactants were above the
reference values in all the patients, and were
decreased at T2 (P < 0.05). Increase of GPx
activity after zinc supplementation in patients
with retinopathy. Conclusions: Zinc deficiency in
insulin-dependent diabetic patients is corrected by
a zinc supplementation. Moreover this
supplementation decreases lipid peroxidation. The
effects of zinc are different in diabetic patients
with or without retinopathy. The increase in Se-GPx
activity observed in patients with retinopathy
could be linked to the protective effect of zinc on
the protein itself.
FUNDAM. APPL. TOXICOL. (USA), 1992, 19/4
(512-520) The effect of chronic dietary zinc deficiency on
the carcinogenic potential of dietary cadmium was
assessed in male Wistar (WF/NCr) rats. Groups (n =
28) of rats were fed diets adequate (60 ppm) or
marginally deficient (7 ppm) in zinc and containing
cadmium at various levels (0, 25, 50, 100, or 200
ppm). Lesions were assessed over the following 77
weeks. Zinc deficiency alone had no effect on
survival, growth, or food consumption. Cadmium
treatment did not reduce survival or food
consumption and only at the highest doses of
cadmium (100 and 200 ppm) was body weight reduced
(maximum 17%). The incidence of prostatic
proliferative lesions, both hyperplasias and
adenomas, was increased over that seen in controls
(1.8%) in both zinc-adequate (20%) and
zinc-deficient rats (14%) fed 50 ppm cadmium. The
overall incidence for prostatic lesions for all
cadmium treatment groups was, however, much lower
in zinc-deficient rats, possibly because of a
marked increase in prostatic atrophy that was
associated with reduced zinc intake. Cadmium
treatment resulted in an elevated leukemia
incidence (maximum 4.8-fold over control) in both
zinc-adequate and zinc-deficient groups, although
zinc deficiency reduced the potency of cadmium in
this respect. Testicular tumors were significantly
elevated only in rats receiving 200 ppm cadmium and
diets adequate in zinc. Both zinc-deficient and
zinc-adequate groups showed significant positive
trends for development of testicular neoplasia with
increasing cadmium dosage. Thus, oral cadmium
exposure is clearly associated with tumors of the
prostate, testes, and hematopoietic system in rats,
while dietary zinc deficiency has complex,
apparently inhibitory, effects on cadmium
carcinogenesis by this route.
BR. J. UROL. (ENGLAND), 1983,
55/5 (525-528) The serum zinc, vitamin A,
albumin, copper and retinoid-binding protein
content was measured in 27 patients with benign
prostatic hyperplasia and 19 patients with
carcinoma of the prostate. A significantly lower (P
= < 0.05) level of serum zinc was found in the
cancer group as well as a significant zinc/vitamin
A correlation (P = < 0.05). The possible
significance of this in relation to the
pathogenesis of carcinoma of the prostate is
discussed.
Friis H; Ndhlovu P; Mduluza T; Kaondera K; Sandstrom B; Michaelsen KF; Vennervald BJ; Christensen NO Danish Bilharziasis Laboratory, Denmark. Eur J Clin Nutr (ENGLAND) Jan 1997, 51 (1) p33-7 OBJECTIVES: To assess the effect of zinc
supplementation on susceptibility to S. mansoni
reinfections among schoolchildren. DESIGN:
Randomized, double-blind, placebo-controlled trial.
SETTING AND SUBJECTS: 313 rural Zimbabwean
schoolchildren (144 boys and 169 girls), 11-17 y).
INTERVENTIONS: Supplementation with zinc (or
placebo on schooldays for 12 months. Due to
drought, a food programme was in operation during
the last eight months of the study. OUTCOME
MEASURES: S. mansoni and S. haematobium reinfection
rates and intensities. RESULTS: There was no
difference in reinfection rates between the zinc
and placebo groups (25 vs 29%, P = 0.46). However,
the median intensity of S. mansoni reinfection,
although low in both groups, was significantly
lower in the zinc than in the placebo group (7 vs
13 eggs per gram of faeces, P = 0.048). No
difference in either S. haematobium reinfection
rates or intensities were seen. CONCLUSIONS: Zinc
supplementation reduced the intensity of S. mansoni
reinfections. Although the intensities of
reinfection were very low, the finding probably
reflects a biological effect of zinc that could be
of public health importance in settings with higher
transmission.
Wang ZH; Iguchi H; Ohshio G; Imamura T; Okada N; Tanaka T; Imamura M First Department of Surgery, Faculty of Medicine, Kyoto University, Japan. Pancreas (UNITED STATES) Aug 1996, 13 (2)
p173-83 Recent findings have suggested that
oxygen-derived free radicals play an important role
in the development and progression of acute
pancreatitis. Therefore, the present study was
designed to investigate whether metallothionein, a
free radical scavenger, can protect against acute
pancreatitis. Rats were injected intraperitoneally
with zinc, followed by either an infusion of
cerulein at 10 micrograms/kg for 4 h or a
retrograde injection with 100 microliters/100 g
body weight of 5% sodium taurocholate into the
pancreaticobiliary duct, in order to induce acute
pancreatitis. Zn administration significantly
increased the levels of both metallothionein and
reduced glutathione in the pancreas; the
metallothionein levels reached a peak of 83-fold of
normal levels after 24 h. The indications of acute
pancreatitis, as well as the mortality, were
improved by Zn treatment before the onset of acute
pancreatitis. Immunohistochemical studies showed
that metallothionein nd with strong staining around
the periphery of the vacuoles in the group treated
with both Zn and cerulein. These findings suggested
that Zn increased both metallothionein and
glutathione levels in the pancreas and exerted a
beneficial effect against ceruleinor taurocholate-induced
acute pancreatitis in rats.
Garcia Tamayo F; Terrazas Valdes LI; Malpica Lopez N Departamento de Biologia, Facultad de Quimica, Universidad Nacional Autonoma de Mexico, Mexico, D.F. Arch Med Res (MEXICO) Autumn 1996, 27 (3)
p319-25 Experimentally induced chronic stress can
produce severe retardation on the physical
development of young animals. Moreover, the chronic
stress and its associated secondary malnutrition
cause a variable depression on immunity, whose
pathogenesis has been related to the excessive
production of cytokines and glucocorticoids. When
stressful stimuli are excessive, animals increment
their anorexia and express a progressively
installed wasting syndrome, associated with
hypozincemia and susceptibility to infections with
high mortality rate. In this work, chronically
stressed mice were studied to observe the
prophylactic effect of a zinc treatment on the
evolution of both their malnutrition and their
immune competence. Stress was induced in newborn
Balb/c mice by intraperitoneal (IP) injections with
heat-killed bacteria for 4 weeks. Following this
inductive period, almost all the stressed mice
showed a transient wasting syndrome characterized
by anorexia, deficient gain of corporal weight,
diarrhea, skin infection, reduced antibody response
against antigens of red blood sheep cells, and a
decreased proliferative response in their Con-A
stimulated splenic lymphocytes. However, when the
stressed mice received an additional IP treatment
with zinc acetate, their clinical condition showed
a significant improvement and their
immunocompetence was similar to that exhhe control
groups. The results suggest that zinc
supplementation can ameliorate the effects of
chronic stress on the growth, corporal weight, and
immunocompetence of young mice.
Gurney ME; Cutting FB; Zhai P; Andrus PK; Hall ED Central Nervous System Diseases Research Unit, Upjohn Laboratories, Kalamazoo, MI 49001, USA. Pathol Biol (Paris) (FRANCE) Jan 1996, 44 (1)
p51-6 Oxidative mechanisms of damage have been
implicated indirectly in the damage to brain tissue
caused acutely by ischemia or chronically by
neurodegenerative diseases. A direct link between
pathogenesis and antioxidant enzyme systems has
come from studies of a genetic form of amyotrophic
lateral sclerosis (ALS). ALS causes the
degeneration of motor neurons in cortex, brainstem
and spinal cord with consequent progressive
paralysis and death. The disease occurs in both
sporadic and familial forms. Some 20% of kindreds
in which ALS is inherited in an autosomal dominant
fashion have mutations in the gene (SOD1) encoding
Cu, Zn superoxide dismutase (SOD). Several SOD1
mutations have been shown by ourselves and others
to cause motor neuron disease when expressed at
high levels in transgenic mice, whereas transgenic
mice expressing comparable amounts of wild-type
human SOD do not show clinical disease. Thus, we
have argued that motor neuron disease is caused by
gain-of-function mutations in the human SOD1 gene.
Our current experiments investigate the link
between mutation of SOD1 and oxidative pathways of
damage. (38 Refs.)
Kyriakis SC; Tsinas A; Lekkas S; Sarris K; Bourtzi-Hatzopoulou E Clinic of Medicine, Faculty of Veterinary Medicine, University of Thessaloniki, Macedonia, Greece. Vet Rec (ENGLAND) May 18 1996, 138 (20) p489-92 This field trial was designed to investigate
whether the incorporation of zinc bacitracin into
pig feed would prevent porcine intestinal
adenomatosis. Two hundred-and-eighty-eight weaned
pigs on a farm with a previous history of the
disease were divided into 16 pens of 18 pi
bacitracin were tested: from weaning up to 100 days
of age, either 300 or 200 ppm zinc bacitracin were
incorporated; from 100 to 125 days of age, either
200 or 100 ppm zinc bacitracin were added; and from
125 to 156 days of age (slaughter), either 100 or
50 ppm zinc bacitracin were added. The results were
compared with a positive control group which
received 60, 60 and 30 ppm salinomycin during the
same periods, and with a negative control group
which received no antibacterial and/or performance
enhancer. The mortality, diarrhoea scores, average
daily weight gains, average daily feed intakes and
feed conversion ratios of the pigs were assessed.
At slaughter, samples of ileum were taken from
eight randomly selected pigs per group for
bacteriological and histopathological examinations.
The three treated groups all performed better than
the control group, and the group receiving the high
dose regimen of zinc bacitracin performed
significantly better than the groups receiving the
low dose of zinc bacitracin or salinomycin.
Arora AS; Gores GJ Center for Basic Research in Digestive Diseases, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. Semin Liver Dis (UNITED STATES) Feb 1996, 16 (1)
p31-8 Based on current information, we have described
the role that metals play in potentiating and
ameliorating liver I/R injury. To date, most of the
data have focused on the deleterious effects of
free iron in mediating I/R injury. Several
therapeutic strategies have proven useful in animal
models to counteract the effect of iron as a
potentiator of I/R injury. These approaches have
predominantly centered on the role of iron
chelation using DFO and DFO conjugates. The data
suggest that chelation of iron may prove useful in
preventing I/R injury such as occurs in liver
transplantation. Indeed, enough data are now
available to initiate and support clinical trials
(e.g., addition of DFO conjugates to explant
storage solutions). The role of copper, however, is
less well defined. Copper is important for the
function of copper-zinc SOD. However, free copper
may be as injurious as free iron. Further studies
are needed to clarify the role of copper in
I/R-induced hepatocellular necrosis. Selenium has a
well-defined antioxidant role as part of GSH
peroxidase (GSH antioxidant pathway). More recent
data suggest that selenium may also act as an
antioxidant through selenoprotein P, but the role
of selenoprotein P in I/R injury remains to be
defined. Finally, zinc appears to function as an
antioxidant in less well-defined pathways. Further
studies are needed to identify the fundamental
mechanisms by which zinc may ameliorate oxidative
damage during I/R injury. These data demonstrate
that metals play a critical role in I/R injury of
the liver and remain a fruitful area for
investigation and development of therapeutic
strategies. (65 Refs.)
ACTA OBSTET. GYNECOL. SCAND. (Denmark), 1994,
73/6 (452-455) We measured plasma Cu, Zn and Mg levels in 40
women suffering from premenstrual tension syndrome
(PMTS) and in 20 control subjects by atomic
absorption spectrophotometer. Mean plasma Cu, Zn
and Mg levels, the Zn/Cu ratio were 80.2 plus or
minus 6.00 microg/dl, 112.6 plus or minus 8.35
microg/dl, 0.70 plus or minus 0.18 mmol/l, and 1.40
plus or minus 0.10 in the PMTS group; and 77.0 plus
or minus 4.50 microg/dl, 117.4 plus or minus 9.50
microg/dl, 0.87 plus or minus 0.10 mmol/l, and 1.51
plus or minus 0.05 in the control group
respectively. The mean Mg level and the Zn/Cu ratio
were significantly lower in PMTS patients than in
the control group. Plasma Mg and Zn levels were
diminished significantly during the luteal phase
compared to the follicular phase in PMTS group. Mg
deficiency may play a role in the etiology of PMTS.
MED. HYPOTHESES (ENGLAND), 1979, 5/4 (403-414)
Pinealectomy leads to increased formation of
fibrous tissue in the abdominal cavity, increased
skin pigmentation and elevated cholesterol and
alkaline phosphatase levels. It also leads to
reduced formation and/or action of prostaglandin
(PG) E1 and thromboxane (TX) A2. PGE1 plays an
important role in enhancing function of T
suppressor lymphocytes. In primary biliary
cirrhosis there are increased skin pigmentation,
hepatic fibrosis, elevated cholesterol and alkaline
phosphatase levels, defective T lymphocytes and
hyperactive B lymphocytes. Primary biliary
cirrhosis may be a pineal deficiency disease.
Serotonin is important in the pineal and the
serotonin antagonist methysergide may cause
retroperitoneal fibrosis by interfering with pineal
function. These is a good deal of other evidence
which suggests that melatonin PGE1 and TXA2 are
important in the regulation of fibrosis in other
situations such as 'collagen' diseases,
lithium-induced fibrosis and cardiomyopathies. This
suggests that enhancement of formation of PGE1 and
of TXA2 may be of value in diseases associated with
excess fibrosis and defective T suppressor cell
function. PGE1 levels may be raised by zinc,
penicillin, penicillamine and essential fatty
acids. TXA2 levels may be raised by low dose
colchicine. These new approaches to treatment may
prove safer and more effective than existing ones.
They may be of value in disorders such as
cardiomyopathy, Hodgkin's disease and other
lymphomas, multiple sclerosis, Crohn's disease,
atopy and other diseases in which defective T cell
function is suspected.
ACTA NEUROL. SCAND. (Denmark), 1989, 79/5
(373-378) Zinc (Zn), copper (Cu) and magnesium (Mg)
concentrations in cerebrospinal fluid (CSF) and
serum were determined with atomic absorption
spectrophotometry in 74 patients suffering from
various neurological diseases, and in 28 healthy
controls. Increased CSF zinc levels were found in
the group of peripheral nervous system diseases (P
< 0.01) and in the cases of different neurological
syndromes with increased CSF protein concentration
(P < 0.001). Increased CSF and serum copper levels
were found in the cases with increased CSF protein
levels (P < 0.05). It is probable that damaged
blood-brain-barrier (BBB) permits the passage of
the trace elements Zn, Cu and of Mg into the
subarachnoid space. Decreased serum Cu levels (P <
0.01) were found in the group of multiple sclerosis
(MS). The findings are correlated to those of
previous communications.
Neurochem Int (ENGLAND) Jul 1995, 27 (1) p1-22
Many, but not all, zinc-containing neurons in
the brain are a subclass of the glutamatergic
neurons, and they are found predominantly in the
telencephalon. These neurons store zinc in their
presynaptic terminals and release it by a
calcium-dependent mechanism. These "vesicular"
pools of zinc are viewed as endogenous modulators
of ligand- and voltage-gated ion channels.
Metallothioneins (MTs) are low molecular weight
zinc-binding proteins consisting of 25-30% cysteine,
with no aromatic amino acids or disulfide bonds.
The areas of the brain containing high contents of
zinc such as the retina, the pineal gland, and the
hippocampus synthesize unique isoforms of MT on a
continuous basis. The four MT isoforms are thought
to provide the neurons and glial elements with
mechanisms to distribute, donate, and sequester
zinc at presynaptic terminals; or buffer the excess
zinc at synaptic junctions. In this cause,
glutathione disulfide may participate in releasing
zinc from MT. A similar nucleotide and amino acid
sequence has made it difficult to obtain cDNA
probes and antibodies capable of distinguishing
indisputably among MT isoforms. MT-I and MT-II
isoforms are found in the brain and in the
peripheral tissues; MT-III isoform, possessing an
additional seven amino acids, is expressed mostly
in the brain and to a very minute extent in the
intestine and pancreas; whereas MT-IV isoform is
found in tissues containing stratified squamous
epithelial cells. Since MTs are expressed in
neurons that sequester zinc in their synaptic
vesicles, the regulation of the expression of MT
isoforms is extremely important in terms of
maintaining the steady-state level of zinc and
controlling redox potentials. The concentration of
zinc has been shown to be altered in an extensive
number of disorders of the central nervous system,
including alcoholism. Alzheimer-type dementia,
amyotrophic lateral sclerosis, Down's syndrome,
epilepsy, Friedreich's ataxia, Guillaine-Barre
syndrome, hepatic encephalopathy, multiple
sclerosis, Parkinson's disease, Pick's disease,
retinitis pigmentosa, retinal dystrophy,
schizophrenia, and Wernicke-Korsakoff syndrome. The
status of MT isoforms and other low molecular
weight zinc-binding proteins in these conditions,
diseases, disorders, or syndromes is being
delineated at this time. Since several of these
disorders, such as amyotrophic lateral sclerosis,
are associated with oxidative stress, and since MT
is able to prevent the formation of free radicals,
it is believed that cytokine-induced induction of
MT provides a long-lasting protection to avert
oxidative damage.
Experimental Eye Research (United Kingdom),
1996, 62/4 (399-408) Initial investigations done in this laboratory
detected increased albumin and decreased
glyceraldehyde 3-phosphate dehydrogenase
concentrations in the retina of an animal model
manifesting early onset macular degeneration. Both
glyceraldehyde 3-phosphate dehydrogenase and
albumin are markers of oxidative stress in cells.
In this study, we used the same animal model to
study further biochemical and physiological
processes which may be involved in the pathogenesis
of early onset macular degeneration in monkeys. We
detected 60% lower catalase and glutathione
peroxidase activities in the affected retinas
suggesting lower antioxidant activities and
oxidative stress. One of the consequences of
oxidative stress is the production of
metallothionein, a low molecular weight protein
also induced by high concentrations of heavy metals
such as zinc. Metallothionein was detected by
RT-PCR in these monkey retinas. However initial
quantitative PCR studies on this protein showed
that the synthesis of metallothionein in affected
retinas appears to be less than in normal controls.
The affected retinas also showed a fourfold lower
zinc concentration compared with the normal
controls. No significant difference, however, could
be detected in the zinc concentrations in plasma
samples. Since induction of metallothionein
synthesis is mediated by transcription factors
which require heavy metals such as zinc for binding
to specific sites in the DNA, the lowered zinc
concentration may, thus, correlate with the lowered
metallothionein expression. And since
metallothionein is suggested to function as a free
radical scavenger, the lowered metallothionein
synthesis may consequently contribute to increased
peroxidation reactions in the affected retinas. It
appears therefore, that oxidative stress and the
decreased metallothionein synthesis may be involved
in the pathogenesis of early onset macular
degeneration in this animal model.
Arch Ophthalmol (UNITED STATES) Aug 1996, 114
(8) p991-7 OBJECTIVE: To quantify relationships between
dietary intake of zinc and antioxidant nutrients
and early and late age-related maculopathy (ARM).
DESIGN: A retrospective longitudinal cohort design
using data pertaining to diets in the past
(1978-1980), which were assessed retrospectively
using a food frequency questionnaire. SETTING:
Beaver Dam, Wis. PATIENTS: A 50% random sample of
free-living Beaver Dam Eye Study participants, 43
to 86 years of age (N = 1968). MAIN OUTCOME
MEASURE: The presence of early and late ARM
determined from fundus photography. RESULTS: People
in the highest vs lowest quintiles for intake of
zinc from foods had lower risk for early ARM (odds
ratio = 0.6, 95% confidence interval, 0.4-1.0, P
for trend < .05). This relationship appeared to be
stronger for some types of early ARM (increased
retinal pigment) than for others. Zinc intake was
unrelated to late ARM. However, small numbers (n =
30) of people with this condition limit the ability
to draw conclusions about this later stage. Levels
of carotenoids were unrelated to early or late ARM.
Odds for early ARM were lower in people in the
highest vs lowest quintiles for the intake of
vitamins C or E. However, these associations were
not statistically significant. CONCLUSIONS: The
data are weakly supportive of a protective effect
of zinc on the development of some forms of early
ARM. Prospective studies are needed to further
evaluate the potential influence of these and other
nutritional factors on different types and stages
of age-related macular degeneration.
Invest Ophthalmol Vis Sci (UNITED STATES) Jun
1996, 37 (7) p1225-35 PURPOSE. To investigate the short-term effect of
oral zinc substitution on the development of
age-related macular degeneration in the second eye
of patients with an exudative form of the disease
in the first eye. METHODS. A 2-year, double-masked,
randomized, placebo-controlled study including 112
white patients with age-related macular
degeneration and exudative lesions (choroidal
neovascularization, pigment epithelial detachment,
or both) in one eye and a visual acuity of better
than 20/40 and macular degeneration without any
exudative lesion in the second eye was performed.
Patients received either 200 mg of oral zinc
sulfate or placebo once daily for 24 months. The
main outcome parameters were visual acuity,
contrast sensitivity, color discrimination, and
retinal grating acuity, as well as serum levels of
zinc and copper, red blood cell count, hemoglobin,
and morphologic changes detected by grading of
monochrome fundus photographs and fluorescein
angiograms. RESULTS. In the treatment group, the
mean zinc serum level increased significantly (P <
0.0001) from 79 +/- 10 micrograms/dl to 108 +/- 26
micrograms/dl compared to no change (82 +/- 16
micrograms/dl to 85 +/- 10 micrograms/dl) in the
placebo group. Serum levels of copper, hemoglobin,
and red blood cell count did not change
significantly in either group. A choroidal
neovascular membrane (CNV) was detected in 14
patients during the treatment period (nine in the
treatment group, five in the placebo group). Seven
additional patients (three in the treatment group,
four in the placebo group) experienced visual loss
caused by CNV, and in two patients (one in each
group), serous pigment epithelial detachment
developed without angiographic evidence of CNV
after the end of treatment, during a mean
additional follow-up time of 20.8 +/- 8.2 months.
In eyes in which exudative lesions did not develop,
there was no significant change in any of the
functional parameters during the 24-month treatment
period, but there was a significant increase in the
nonexudative alterations (drusen size, drusen
confluence, hyperpigmentation, and focal
degeneration of the retinal pigment epithelium) in
both groups. CONCLUSIONS. Oral zinc substitution
has no short-term effect on the course of
age-related macular degeneration in patients who
have an exudative form of the disease in one eye.
Proceedings of the Association of American
Physicians (USA), 1997, 109/1 (68-77) 50X Cell-mediated immune dysfunctions and
susceptibility to infections have been observed in
zinc-deficient human subjects. In this study, we
investigated the production of cytokines and
characterized the T-cell subpopulations in three
groups of mildly zinc-deficient subjects. These
included head and neck cancer patients, healthy
volunteers who were found to have a dietary
deficiency of zinc, and healthy volunteers in whom
we induced zinc deficiency experimentally by
dietary means. We used cellular zinc criteria for
the diagnosis of zinc deficiency. We assayed
enzyme-linked immunosorbent assay the production of
cytokines from phytohemagglutinin- stimulated
peripheral blood mononuclear cells and assessed by
flow cytometry the differences in T-cell
subpopulations. Our studies showed that the
cytokines produced by TH1 cells were particularly
sensitive to zinc status, inasmuch as the
production of interleukin-2 (IL-2) and
interferon-gamma were decreased even though the
deficiency of zinc was mild in our subjects. TH2
cytokines (IL-4, IL-5, and IL-6) were not affected
by zinc deficiency. Natural killer cell lytic
activity also was decreased in zinc-deficient
subjects. Recruitment of naive T cells (CD4+CD45
RA+) and CD8+ CD73+ CD11b-, precursors of cytolytic
T cells, were decreased in mildly zinc-deficient
subjects. An imbalance between the functions of TH1
and TH2 cells and changes in T-cell subpopulations
are most probably responsible for cell-mediated
immune dysfunctions in zinc deficiency.
Indian Journal of Leprosy (India), 1996, 68/4
(349-361) Immunotherapy aims to modify the defective
cell-mediated immune response in a section of
leprosy cases. This presentation reviews the
various immunomodulators developed/investigated for
this purpose. Among the various mycobacterial
agents, BCG, BCG + M. leprae, Mycobacterium w, ICRC
bacillus and M. vaccae have been tried in leprosy
patients and varying degrees of beneficial effects
on bacterial killing and clearance have been
observed. Studies carried out at CJIL, Agra and
elsewhere suggest an important role for these
mycobacteria as immunotherapeutic agents. Other
mycobacteria - M. habana, M. phlei, M. gordonae -
have also been reported to be promising
experimentally. In addition, various drugs such as
levamisole, zinc and RACA 854 have been observed to
have immunomodulatory role in leprosy cases. Other
promising immunomodulators include transfer factor,
interferon gamma, interleukin 2 and acetoacetylated
M. leprae. The progress achieved shows that
immunotherapy may be considered as adjunct to
chemotherapy to enhance bacterial killing as well
as bacterial clearance and thus may be recommended
to shorten the treatment period, especially in
bacilliferous leprosy cases.
Cahiers Sante (France), 1996, 6/4 (201-208) In developing countries, more than 123 million
children die each year from the combined effects of
malnutrition and infection. Malnourished children
have impaired cellular immunity and are
particularly sensitive to opportunistic infections.
However, immune recovery has rarely been
investigated during nutritional rehabilitation.
Indeed, mortality remains high during renutrition,
and relapses are frequent. We established a center
in Cochabamba, Bolivia, specifically to save these
children by treating both clinical and nutritional
problems and restoring immune function. The CRIN
(center for immuno-nutritional recovery) admits
children with severe malnutrition from the
Cochabamba suburban area. They are from low income
families, in crowded living conditions with poor
sanitation and are weaned early. Nutritional
diagnosis was based on weight-for-height, arm to
head circumference ratio and clinical examination
for edema, loss of subcutaneous tissue and
diminished muscle mass. The children were examined
daily and first treated for respiratory and
intestinal infections. Sociological and
psychological aspects were also included in our
holistic approach to treating severe malnutrition.
Children received a four-stage diet lasting 2
months. During the initial phase (1 week) they were
given an oil-sugar-mild based diet, with half
lactose concentration, seven times a day. This
supplied 1.5 to 2.5 g of protein and 120 to 150
kcal/kg of body weight, according to the PEM
pattern. Protein and energy intake was then slowly
increased during the transition phase (1 week).
During the next, 'calorific-protein bombing' phase
(6 weeks) 5 g of protein and 200 kcal/kg of body
weight were given daily, such that there was
sufficient energy for protein accumulation. During
the last, discharge phase (1 week), the protein and
energy contents were slowly decreased. Weight,
height, arm and head circumferences, and triceps
skin-fold thickness were measured weekly by
standardized methods. Thymus size was assessed
weekly by mediastinal ultrasound scanning with a
portable scanner (ALOKA SSD-210 DXII, Tokyo) using
a 5 MHz linear pediatric probe. Lymphocyte
subpopulations in peripheral blood were
investigated monthly using monoclonal antibodies.
Compared to controls, the malnourished group had
severe involution of the thymus, a significantly
higher proportion of circulating immature T
lymphocytes and a lower proportion of mature T
lymphocytes. The two month longitudinal study
showed that normal anthropometric values (90% NCHS
weight for height) were recovered after one month
of rehabilitation. However, immune recovery (thymic
area of 350 mm2) required two months. This may
explain the frequent relapses among malnourished
children discharged after one month on the basis of
'apparent nutritional health'. Such children may
remain immunodepressed, and should therefore be
considered as high risk children. To test an
immunostimulatory treatment, we designed a
historical cohort study of malnourished children
who received 2 mg of zinc per day. The children
were matched for age, sex, anthropometric criteria
and nutritional status with malnourished control
children (treated previously without zinc).
Anthropometric recovery was obtained in both groups
in one month. Children receiving zinc attained
immunological recovery within one month, whereas
children not receiving zinc took two months. Thus
zinc hastened immunological recovery concomitant
with nutritional recovery such that the duration of
hospitalization could be halved: after one month of
this immuno-nutritional treatment, malnourished
children appear to be sufficiently healthy to face
their pathogenic home environment.
Journal of Nutritional Biochemistry (USA), 1996,
7/6 (327-332) The effects of gestational Mg or Zn deficiency
on the humoral or cellular immunity of newborn rats
were investigated. Mg deficiency was induced by
feeding a diet containing 180 ppm Mg from day 0 to
day 21 of gestation and Zn deficiency was induced
by feeding a diet containing 1.5 ppm Zn from day 0
to day 19. Controls were fed a diet with 1,000 ppm
Mg and 100 ppm Zn from day 0 to day 21. Thereafter,
all maternal rats and newborns were fed diets with
normal amounts of Mg or Zn. Three and six weeks
after birth, T-cell subpopulations in blood and
thymus and B-cells in blood of the newborns were
detected by flow cytometry. Plasma contents of IgG,
IgM, and IgA were determined by radial
immunodiffusion. Mg deficiency reduced litter size
and pup weight. Three weeks after birth, the total
number of leukocytes and lymphocytes in blood was
significantly decreased, due to a reduction of
T-helper and cytotoxic T-cells. Activated T-cells
and B-cells were unchanged. Six weeks after birth,
T-cell subpopulations approached controls values,
whereas IgG content in plasma was slightly reduced.
Gestational Zn deficiency reduced litter size and
induced malformations. Three and six weeks after
birth, body weight, number of leukocytes,
lymphocyte, and T-cell subpopulations were not
significantly changed. Plasma IgM was decreased 3
weeks after birth in correlation to the number of
B-cells, which represented only 4% of total
lymphocytes. These effects were repaired by the
sixth week. Plasma IgG was reduced at 6 weeks. No
effects on T-cell subpopulations in isolated
thymocytes were detected after gestational Mg or Zn
deficiency.
European Journal of Clinical Nutrition (United
Kingdom), 1996, 50/1 (42-46) Objective: To assess the effect of zinc
supplementation on respiratory tract disease,
immunity and growth in malnourished children.
Design: A randomized double-blind
placebo-controlled trial. Setting: A day-care
center in Quite, Ecuador. Subjects: Fifty children
(12-59 months old) recruited by height-for-age and
weight-for-age deficit. Interventions: Twenty-five
children (supplemented, S group) received 10 mg/day
of zinc as zinc sulfate, and 25 (nonsupplemented,
NS group) received a placebo during 60 days. All
were also observed during a 60-day
postsupplementation period. Two children of the S
group dropped out. Daily the clinical presence of
cough, respiratory tract secretions, and fever, was
recorded. On days 0, 60 and 120, the cutaneous
delayed-type hypersensitivity (DTH) to multiple
antigens, and anthropometric parameters were
assessed. On days 0 and 60 serum zinc levels were
also measured. Results: On day 60, DTH was
significantly larger (20.8 plus or minus 7.1 vs
16.1 plus or minus 9.7 mm), and serum zinc levels
were significantly higher (118.6 plus or minus 47.1
vs 83.1 plus or minus 24.5 microg/dl) in the S
group than in the NS group (P < 0.05 for each). The
incidence of fever (relative risk (RR): 0.30, c.i.
= 0.08-0.95, P = 0.02), cough (RR): 0.52, c.i. =
0.32-0.84, P = 0.004) and upper respiratory tract
secretions (RR):0.72, c.i. = 0.59-0.88, P = 0.001)
was lower in the S group than in the NS group at
day 60. At the end of the postsupplementation
observation period (day 120), the incidence of
fever and upper respiratory tract secretions was
the same in both the S and NS groups. The incidence
of cough was higher at day 120 in the S group than
in the NS group (RR): 2.28, c.i. = 1.37-3.83, P =
0.001). Conclusions: This study supports a role for
zinc in immunity, and immunity to respiratory
infections, while pointing out the need for larger
studies.
J Neuroimmunol (NETHERLANDS) Sep 1994, 53 (2)
p189-201 It has been demonstrated that melatonin, the
main neuro-hormone of the pineal gland, affects
thymic functions and the regulation of the immune
system. In addition, experimental evidences
indicate that melatonin can modulate zinc turnover.
The knowledge that with advancing age both
melatonin and zinc plasma levels decline, and that
zinc supplementation in old mice is able to restore
the reduced immunological functions, has prompted
investigations on the effect of chronic melatonin
treatment or pineal graft in old mice on the
age-related decline of thymic endocrine activity,
peripheral immune functions and zinc turnover. Both
melatonin treatment in old mice and pineal graft
into the thymus of old mice correct the reduced
thymic endocrine activity and increase the weight
of the thymus and its cellularity. A restoration of
cortical thymic volume, as detected by the
percentage of tissue in active proliferation, is
also observed in old mice after both treatments.
Thymocyte CD phenotype expression is also restored
to young values. At peripheral level, recovery of
peripheral blood lymphocyte number and of spleen
cell subsets, with increased mitogen responsiveness
also occurs. Melatonin treatment or pineal graft
induce also a restoration of the altered zinc
turnover in aged mice with an increment of the
crude zinc balance from negative (-1.6
microgram/day/mouse) to positive value (+1.2
microgram/day/mouse), similar to that one of young
mice (+1.4 microgram/day/mouse). The reduced zinc
plasma level is restored to normal values. These
findings support the idea that the effect of
melatonin on thymic endocrine activity and
peripheral immune functions may be mediated by the
zinc pool.
Med Hypotheses (ENGLAND) Apr 1993, 40 (4) p250-6 'Magnesium ischaemia' is a term used to denote
the functional impairment of the ATP-dependent
sodium/potassium and calcium pumps in the cell
membranes and within the cell itself. The
production of ATP and the functioning of these
pumps is magnesium-dependent and is critically
sensitive to acidosis. Zinc and iron deficiencies
may secondarily impair these pumps and thus
contribute to 'magnesium ischaemia' (as does
acidosis). This term is two-dimensional at its
simplest; it refers to a functional magnesium
deficiency, whether actual or induced. It is argued
that chronic acidosis is the most common inducing
factor. This simple hypothesis can begin to unify
diverse pathophysiologies: some spontaneous
abortions, aspects of Type II and gestational
diabetes and the curious observation that heroin
addicts become diabetic. It can also unify clinical
thinking about pregnancy-induced hypertension, pre-eclampsia/eclampsia
and acute fatty liver of pregnancy, as well as the
coagulopathy of pregnancy. It makes important
predictions about perinatal morbidity and suggests
that early supplementation might prevent much
pregnancy-induced disease.
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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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 a |
