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Biomedical subjects

M J Vimy

Publications and source records attributed to M J Vimy.

At least 19 recordsLinked to original sources
PubMed1997

Metallothionein induction in fetal rat brain and neonatal primary astrocyte cultures by in utero exposure to elemental mercury vapor (Hg0).

Brain metallothionein (MT) protein and mRNA levels were determined in the fetal rat following in utero (gestational days 7-21) exposure to elemental mercury vapor (Hg0; 300 microg Hg/m3; 4 h/day). Total RNA was probed on Northern blots with [alpha-32P]dCTP-labeled synthetic cDNA probes specific for rat MT isoform mRNAs. The probes for MT-I and MT-II mRNA hybridized to a single band of approximately 550 and 450 nucleotides, respectively. Expression of whole brain MT-I mRNA in full-term fetal rats (day 21) was significantly increased (P < 0.03) by in utero exposure to Hg0 compared to nonexposed controls. This corresponded to a 14-fold increase (P < 0.001) in fetal brain Hg concentration after in utero Hg0 exposure. In addition, astrocytes from both control and in utero Hg0-exposed fetuses were isolated, and neonatal primary astrocyte cultures were established and maintained in vitro for up to 3 weeks without additional experimental intervention. Astrocyte monolayers derived from in utero Hg0-exposed fetuses consistently expressed increased abundance of MT-I mRNA transcripts after 1, 2, and 3 weeks in culture (P < 0.03, P < 0.01, and P < 0.03, respectively) compared with controls. The abundance of astrocyte MT-II mRNA was unchanged at 1 and 2 weeks in culture, but was significantly increased at 3 weeks in cultures derived from brains of Hg0-exposed fetuses (P < 0.04). Consistent with the increase in MT mRNA, an increase in astrocytic levels of MT proteins was noted by Western blot analysis and MT-immunoreactivity. These studies suggest that in utero exposure to Hg0 induces brain MT gene expression, and that MT mRNAs and their respective proteins are useful quantitative biochemical markers of intrauterine exposure to Hg0, a potentially cytotoxic challenge to astrocytes in the developing brain. It is concluded that induction of MT by fetal/neonatal astrocytes represents an attempt by these glial cells to protect against Hg cytotoxicity in maintaining cerebral homeostasis.

Animals↗
PubMed1997

Mercury from maternal "silver" tooth fillings in sheep and human breast milk. A source of neonatal exposure.

Neonatal uptake of mercury (Hg) from milk was examined in a pregnant sheep model, where radioactive mercury (Hg203)/silver tooth fillings (amalgam) were newly placed. A crossover experimental design was used in which lactating ewes nursed foster lambs. In a parallel study, the relationship between dental history and breast milk concentration of Hg was also examined in 33 lactating women. Results from the animal studies showed that, during pregnancy, a primary fetal site of amalgam Hg concentration is the liver, and, after delivery, the neonatal lamb kidney receives additional amalgam Hg from mother's milk. In lactating women with aged amalgam fillings, increased Hg excretion in breast milk and urine correlated with the number of fillings or Hg vapor concentration levels in mouth air. It was concluded that Hg originating from maternal amalgam tooth fillings transfers across the placenta to the fetus, across the mammary gland into milk ingested by the newborn, and ultimately into neonatal body tissues. Comparisons are made to the U. S. minimal risk level recently established for adult Hg exposure. These findings suggest that placement and removal of "silver" tooth fillings in pregnant and lactating humans will subject the fetus and neonate to unnecessary risk of Hg exposure.

Adult↗
PubMed1997

Mercury vapor inhalation inhibits binding of GTP to tubulin in rat brain: similarity to a molecular lesion in Alzheimer diseased brain.

Hg2+ interacts with brain tubulin and disassembles microtubules that maintain neurite structure. Since it is well known that Hg vapor (Hg0) is continuously released from "silver" amalgam tooth fillings and is absorbed into brain, rats were exposed to Hg0 4h/day for 0, 2, 7, 14 and 28 d at 250 or 300 micrograms Hg/m3 air, concentrations present in mouth air of some humans with many amalgam fillings. Average rat brain Hg concentrations increased significantly (11-47 fold) with duration of Hg0 exposure. By 14 d Hg0 exposure, photoaffinity labelling on the beta-subunit of the tubulin dimer with [alpha 32P] 8N3 GTP in brain homogenates was decreased 41-74%, upon analysis of SDS-PAGE autoradiograms. The identical neurochemical lesion of similar or greater magnitude is evident in Alzheimer brain homogenates from approximately 80% of patients, when compared to human age-matched neurological controls. Total tubulin protein levels remained relatively unchanged between Hg0 exposed rat brains and controls, and between Alzheimer brains and controls. Since the rate of tubulin polymerization is dependent upon binding of GTP to tubulin dimers, we conclude that chronic inhalation of low-level Hg0 can inhibit polymerization of brain tubulin essential for formation of microtubules.

Administration, Inhalation↗
PubMed1995

The dental amalgam mercury controversy--inorganic mercury and the CNS; genetic linkage of mercury and antibiotic resistances in intestinal bacteria.

Mercury (Hg) vapor exposure from dental amalgam has been demonstrated to exceed the sum of all other exposure sources. Therefore the effects of inorganic Hg exposure upon cell function in the brain and in the intestinal bacteria have recently been examined. In rats we demonstrate that ADP-ribosylation of tubulin and actin brain proteins is markedly inhibited, and that ionic Hg can thus alter a neurochemical reaction involved with maintaining neuron membrane structure. In monkeys we show that Hg, specifically from amalgam, will enrich the intestinal flora with Hg-resistant bacterial species which in turn also become resistant to antibiotics.

Animals↗
PubMed1995

Mercury exposure from "silver" tooth fillings: emerging evidence questions a traditional dental paradigm.

For more than 160 years dentistry has used silver amalgam, which contains approximately 50% Hg metal, as the preferred tooth filling material. During the past decade medical research has demonstrated that this Hg is continuously released as vapor into mouth air; then it is inhaled, absorbed into body tissues, oxidized to ionic Hg, and finally covalently bound to cell proteins. Animal and human experiments demonstrate that the uptake, tissue distribution, and excretion of amalgam Hg is significant, and that dental amalgam is the major contributing source to Hg body burden in humans. Current research on the pathophysiological effects of amalgam Hg has focused upon the immune system, renal system, oral and intestinal bacteria, reproductive system, and the central nervous system. Research evidence does not support the notion of amalgam safety.

Animals↗
PubMed1994

Measurement of total mercury in biological specimens by cold vapor atomic fluorescence spectrometry.

An ultrasensitive method for determining total mercury concentrations in biological specimens is a prerequisite for monitoring exposure to chronic low-dose levels of Hg vapor such as those from dental silver amalgam fillings. The clinical consequences of such doses are currently in question. We describe an adaptation of a two-stage gold amalgamation preconcentration step combined with cold vapor atomic fluorescence spectrometric detection for Hg. At Hg concentrations of 40 and 350 nmol/L, the within-day assay CVs were 5% and 3%, respectively; between-day assay CVs were 8% and 5%, respectively. Accuracy, as demonstrated by analytical recovery, ranged from 98% to 105%. The detection limit for the assay is 50 pmol/L, which is suitable for measuring total Hg concentrations in specimens of human urine, blood, and breast milk, and in monkey kidney cortex and feces, obtained from subjects with and without amalgam fillings.

Animals↗
PubMed1993

Mercury released from dental "silver" fillings provokes an increase in mercury- and antibiotic-resistant bacteria in oral and intestinal floras of primates.

In a survey of 640 human subjects, a subgroup of 356 persons without recent exposure to antibiotics demonstrated that those with a high prevalence of Hg resistance in their intestinal floras were significantly more likely to also have resistance to two or more antibiotics. This observation led us to consider the possibility that mercury released from amalgam ("silver") dental restorations might be a selective agent for both mercury- and antibiotic-resistant bacteria in the oral and intestinal floras of primates. Resistances to mercury and to several antibiotics were examined in the oral and intestinal floras of six adult monkeys prior to the installation of amalgam fillings, during the time they were in place, and after replacement of the amalgam fillings with glass ionomer fillings (in four of the monkeys). The monkeys were fed an antibiotic-free diet, and fecal mercury concentrations were monitored. There was a statistically significant increase in the incidence of mercury-resistant bacteria during the 5 weeks following installation of the amalgam fillings and during the 5 weeks immediately following their replacement with glass ionomer fillings. These peaks in incidence of mercury-resistant bacteria correlated with peaks of Hg elimination (as high as 1 mM in the feces) immediately following amalgam placement and immediately after replacement of the amalgam fillings. Representative mercury-resistant isolates of three selected bacterial families (oral streptococci, members of the family Enterobacteriaceae, and enterococci) were also resistant to one or more antibiotics, including ampicillin, tetracycline, streptomycin, kanamycin, and chloramphenicol. While such mercury- and antibiotic-resistant isolates among the staphylococci, the enterococci, and members of the family Enterobacteriaceae have been described, this is the first report of mercury resistance in the oral streptococci. Many of the enterobacterial strains were able to transfer mercury and antibiotic resistances together to laboratory bacterial recipients, suggesting that the loci for these resistances are genetically linked. Our findings indicate that mercury released from amalgam fillings can cause an enrichment of mercury resistance plasmids in the normal bacterial floras of primates. Many of these plasmids also carry antibiotic resistance, implicating the exposure to mercury from dental amalgams in an increased incidence of multiple antibiotic resistance plasmids in the normal floras of nonmedicated subjects.

Animals↗
PubMed1991

Mercury from dental "silver" tooth fillings impairs sheep kidney function.

In humans Hg vapor is released from "silver" amalgam fillings that contain 50% Hg by weight. Previous studies show that when 12 such fillings are placed in sheep teeth, the kidneys will concentrate amalgam Hg at levels ranging from 5 to 10 micrograms Hg/g renal tissue 4-20 wk after placement. In the present study 12 occlusal fillings were placed in each of six adult female sheep under general anesthesia, using standard dental procedures. Glass ionomer occlusal fillings (12) were inserted in two control sheep. At several days before dental surgery, and at 30 and 60 days after placement of fillings, renal function was evaluated by plasma clearance of inulin and by plasma and urine electrolytes, urea, and proteins. An average plasma inulin clearance rate of 69.5 +/- 7.2 ml/min before amalgam placement was reduced to 32.3 +/- 8.1 ml/min by 30 days and remained low at 27.9 +/- 8.7 ml/min after 60 days. Inulin clearance did not change in controls. After amalgam placement urine concentration of albumin decreased from 93.0 +/- 20.5 to 30.1 +/- 15.3 mg/l and urine Na+ concentration increased steadily from 24.8 +/- 7.7 to 82.2 +/- 20.3 mmol/l at 60 days. Concentrations of K+, urea, gamma-glutamyl transpeptidase, alkaline phosphatase, and total protein did not change significantly from 0 to 60 days in urine. Plasma levels of Na+, K+, urea, and albumin remained unchanged from 0 to 60 days after amalgam. Renal histology remained normal in amalgam-treated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Whole-body imaging of the distribution of mercury released from dental fillings into monkey tissues.

The fate of mercury (Hg) released from dental "silver" amalgam tooth fillings into human mouth air is uncertain. A previous report about sheep revealed uptake routes and distribution of amalgam Hg among body tissues. The present investigation demonstrates the bodily distribution of amalgam Hg in a monkey whose dentition, diet, feeding regimen, and chewing pattern closely resemble those of humans. When amalgam fillings, which normally contain 50% Hg, are made with a tracer of radioactive 203Hg and then placed into monkey teeth, the isotope appears in high concentration in various organs and tissues within 4 wk. Whole-body images of the monkey revealed that the highest levels of Hg were located in the kidney, gastrointestinal tract, and jaw. The dental profession's advocacy of silver amalgam as a stable tooth restorative material is not supported by these findings.

Animals↗
PubMed1990

Maternal-fetal distribution of mercury (203Hg) released from dental amalgam fillings.

In humans, the continuous release of Hg vapor from dental amalgam tooth restorations is markedly increased for prolonged periods after chewing. The present study establishes a time-course distribution for amalgam Hg in body tissues of adult and fetal sheep. Under general anesthesia, five pregnant ewes had twelve occlusal amalgam fillings containing radioactive 203Hg placed in teeth at 112 days gestation. Blood, amniotic fluid, feces, and urine specimens were collected at 1- to 3-day intervals for 16 days. From days 16-140 after amalgam placement (16-41 days for fetal lambs), tissue specimens were analyzed for radioactivity, and total Hg concentrations were calculated. Results demonstrate that Hg from dental amalgam will appear in maternal and fetal blood and amniotic fluid within 2 days after placement of amalgam tooth restorations. Excretion of some of this Hg will also commence within 2 days. All tissues examined displayed Hg accumulation. Highest concentrations of Hg from amalgam in the adult occurred in kidney and liver, whereas in the fetus the highest amalgam Hg concentrations appeared in liver and pituitary gland. The placenta progressively concentrated Hg as gestation advanced to term, and milk concentration of amalgam Hg postpartum provides a potential source of Hg exposure to the newborn. It is concluded that accumulation of amalgam Hg progresses in maternal and fetal tissues to a steady state with advancing gestation and is maintained. Dental amalgam usage as a tooth restorative material in pregnant women and children should be reconsidered.

Animals↗
PubMed1989

Dental "silver" tooth fillings: a source of mercury exposure revealed by whole-body image scan and tissue analysis.

Mercury (Hg) vapor is released from dental "silver" tooth fillings into human mouth air after chewing, but its possible uptake routes and distribution among body tissues are unknown. This investigation demonstrates that when radioactive 203Hg is mixed with dental Hg/silver fillings (amalgam) and placed in teeth of adult sheep, the isotope will appear in various organs and tissues within 29 days. Evidence of Hg uptake, as determined by whole-body scanning and measurement of isotope in specific tissues, revealed three uptake sites: lung, gastrointestinal, and jaw tissue absorption. Once absorbed, high concentrations of dental amalgam Hg rapidly localize in kidneys and liver. Results are discussed in view of potential health consequences from long-term exposure to Hg from this dental material.

Absorption↗