Month: July 2015

Chelation therapy for patients with elevated body lead burden and progressive renal insufficiency. A randomized, controlled trial.

Chelation therapy for patients with elevated body lead burden and progressive renal insufficiency. A randomized, controlled trial.

Lin JL1, Ho HH, Yu CC, 1999

lab-work-1575843-640x960Abstract

BACKGROUND:

Nephropathy is known to occur in persons exposed to high levels of lead, but the question of whether long-term exposure to low levels of environmental lead is associated with impaired renal function remains controversial.

OBJECTIVE:

To examine whether chelation therapy slows the progression of renal insufficiency in patients with mildly elevated body lead burden.

DESIGN:

Randomized, controlled trial.

SETTING:

Academic medical center in Taiwan.

PATIENTS:

32 patients with chronic renal insufficiency (serum creatinine level > 132.6 micromol/L [1.5 mg/dL] and < 353.8 micromol/L [4.0 mg/dL]), mildly elevated body lead burden (> 0.72 micromol [150 microg] of lead per 72-hour urine collection and < 2.90 micromol [600 microg] of lead per 72-hour urine collection [EDTA mobilization tests]), and no history of heavy lead exposure.

INTERVENTION:

The treatment group received 2 months of chelation therapy; the control group received no therapy.

MEASUREMENTS:

The reciprocal of serum creatinine (1/Cr) was used as an index of progressive renal insufficiency.

RESULTS:

Rates of progression of renal insufficiency were similar in the treatment group and the control group during a 12-month baseline observation period (1/Cr, 0.000054 L/micromol per month compared with 0.000046 L/micromol per month; P > 0.2). After the 2-month treatment period, improvement in renal function was greater in the treatment group than in the control group. In the 12 months after the treatment period, renal insufficiency progressed more slowly in the treatment group than in the control group (1/Cr, 0.000033 +/- 0.00038 L/micromol per month compared with 0.000045 +/- 0.000038 L/micromol per month; P = 0.0030).

CONCLUSION:

Chelation therapy seems to slow the progression of renal insufficiency in patients with mildly elevated body lead burden. This implies that long-term exposure to low levels of environmental lead may be associated with impaired renal function in patients with chronic renal disease.

The role of mercury and cadmium heavy metals in vascular disease, hypertension, coronary heart disease, and myocardial infarction.

by Houston MC

medical-doctor-1236728-639x717Abstract

Mercury, cadmium, and other heavy metals have a high affinity for sulfhydryl (-SH) groups, inactivating numerous enzymatic reactions, amino acids, and sulfur-containing antioxidants (NAC, ALA, GSH), with subsequent decreased oxidant defense and increased oxidative stress. Both bind to metallothionein and substitute for zinc, copper, and other trace metals reducing the effectiveness of metalloenzymes. Mercury induces mitochondrial dysfunction with reduction in ATP, depletion of glutathione, and increased lipid peroxidation; increased oxidative stress is common. Selenium antagonizes mercury toxicity. The overall vascular effects of mercury include oxidative stress, inflammation, thrombosis, vascular smooth muscle dysfunction, endothelial dysfunction, dyslipidemia, immune dysfunction, and mitochondrial dysfunction. The clinical consequences of mercury toxicity include hypertension, CHD, MI, increased carotid IMT and obstruction, CVA, generalized atherosclerosis, and renal dysfunction with proteinuria. Pathological, biochemical, and functional medicine correlations are significant and logical. Mercury diminishes the protective effect of fish and omega-3 fatty acids. Mercury, cadmium, and other heavy metals inactivate COMT, which increases serum and urinary epinephrine, norepinephrine, and dopamine. This effect will increase blood pressure and may be a clinical clue to heavy metal toxicity. Cadmium concentrates in the kidney, particularly inducing proteinuria and renal dysfunction; it is associated with hypertension, but less so with CHD. Renal cadmium reduces CYP4A11 and PPARs, which may be related to hypertension, sodium retention, glucose intolerance, dyslipidemia, and zinc deficiency. Dietary calcium may mitigate some of the toxicity of cadmium. Heavy metal toxicity, especially mercury and cadmium, should be evaluated in any patient with hypertension, CHD, or other vascular disease. Specific testing for acute and chronic toxicity and total body burden using hair, toenail, urine, serum, etc. with baseline and provoked evaluation should be done.

http://www.ncbi.nlm.nih.gov/pubmed/17405690

Inhibition of paraoxonase activity in human liver microsomes by exposure to EDTA, metals and mercurials.

Gonzalvo MC1, Gil F, Hernández AF, Villanueva E, Pla A. 1997

Abstract

lab-work-1575846-640x960Inhibition of paraoxon hydrolase (paraoxonase) activity by ‘in vitro’ exposure to EDTA, Mg2+, Co2+, Ba2+, La3+, Zn2+, Cu2+, Hg2+, p-hydroxymercuribenzoate (p-OH-MB) and phenyl mercuric acetate (PMA) was investigated in human liver microsomes. Enzyme activity was totally inhibited by 1 mM EDTA in a time-dependent manner, in contrast to previous data obtained in rat liver where an EDTA-resistant fraction was detected. The possible influence of postmortem changes in these results was checked in a parallel experiment using rat livers with different postmortem intervals. From our results the existence in human liver of an EDTA-resistant fraction cannot be discarded. Ba, La and PMA showed immediate inhibition. By contrast the other compounds tested were time-dependent inhibitors. Ba and Zn showed the highest IC50 values. Cu and mercurials (Hg, p-OH-MB, PMA) were the most potent inhibitors of human liver paraoxonase. Kinetic analysis (Lineweaver-Burk and Dixon plots) indicated that different inhibitors exhibit different inhibition patterns: competitive (EDTA, Ba, La, Cu, p-OH-MB and PMA), non competitive (Zn) and mixed (Hg). The pretreatment of sample with dithiothreitol (DTT) protects against the inhibitory effect of mercurials. Furthermore after inhibition by mercurials the activity was restored by DTT. These results confirmed the essential role of the -SH groups to maintain the catalytic activity of paraoxonase and suggest the existence of two types of -SH groups that could differ in their localization.

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Mercury, Fish Oils, and the Risk of Myocardial Infarction

Eliseo Guallar, M.D., et al., 2002

fish-1327431-1279x900Background

It has been suggested that mercury, a highly reactive heavy metal with no known physiologic activity, increases the risk of cardiovascular disease. Because fish intake is a major source of exposure to mercury, the mercury content of fish may counteract the beneficial effects of its n–3 fatty acids…

Read More:

http://www.nejm.org/doi/full/10.1056/NEJMoa020157

Chelation Therapy for Patients with Elevated Body Lead Burden and Progressive Renal Insufficiency: A Randomized, Controlled Trial

Ja-Liang Lin, MD; Huei-Huang Ho, MD; and Chun-Chen Yu, MD

Background: Nephropathy is known to occur in persons exposed to high levels of lead, but the question of whether long-term exposure to low levels of environmental lead is associated with impaired renal function remains controversial.

Objective: To examine whether chelation therapy slows the progression of renal insufficiency in patients with mildly elevated body lead burden.

Design: Randomized, controlled trial.

Setting: Academic medical center in Taiwan.

Patients: 32 patients with chronic renal insufficiency (serum creatinine level > 132.6 µmol/L [1.5 mg/dL] and < 353.8 µmol/L [4.0 mg/dL]), mildly elevated body lead burden (>0.72 µmol [150 µg] of lead per 72-hour urine collection and < 2.90 µmol [600 µg] of lead per 72-hour urine collection [EDTA mobilization tests]), and no history of heavy lead exposure.

Intervention: The treatment group received 2 months of chelation therapy; the control group received no therapy.

Measurements: The reciprocal of serum creatinine (1/Cr) was used as an index of progressive renal insufficiency.

Results: Rates of progression of renal insufficiency were similar in the treatment group and the control group during a 12-month baseline observation period (1/Cr, 0.000054 L/µmol per month compared with 0.000046 L/µmol per month; P > 0.2). After the 2-month treatment period, improvement in renal function was greater in the treatment group than in the control group. In the 12 months after the treatment period, renal insufficiency progressed more slowly in the treatment group than in the control group (1/Cr, 0.000033 ± 0.kidney-beans-1558781-640x96000038 L/µmol per month compared with 0.000045 ± 0.000038 L/µmol per month; P = 0.0030).

Conclusion: Chelation therapy seems to slow the progression of renal insufficiency in patients with mildly elevated body lead burden. This implies that long-term exposure to low levels of environmental lead may be associated with impaired renal function in patients with chronic renal disease.

 

Full Content Available for Subscribers: http://annals.org/article.aspx?articleid=712437

Nickel Concentrations in Serum of Patients with Acute Myocardial Infarction or Unstable Angina Pectoris.

Leach CN Jr, Linden JV, Hopfer SM, Crisostomo MC, Sunderman FW Jr.

Abstract

Nickel was measured, by electrothermal atomic absorption spectrophotometry, in sera from (a) 30 healthy adults, (b) 54 patients with acute myocardial infarction, (c) 33 patients with unstable angina pectoris without infarction, and (d) five patients with coronary atherosclerosis who developed cardiac ischemia during treadmill exercise. Mean (and SD) concentrations in Group a were 0.3 (0.3) microgram/L (range less than 0.05-1.1 microgram/L). Within 72 h after hospital admission, hypernickelemia (Ni greater than or equal to 1.2 microgrheart-1414885-639x650am/L) was found in 41 patients of group b (76%) and in 16 patients of group c (48%). Hypernickelemia was found before and after exercise in one patient of Group d (20%). Peak values averaged 3.0 micrograms/L (range 0.4-21 micrograms/L) in Group b, 1.5 microgram/L (range less than 0.05-3.3 micrograms/L) in Group c. In Group b, the mean time interval between the peak values for creatine kinase activity and for nickel was 18 h. Serum nickel concentrations were unrelated to age, sex, time of day, cigarette smoking, medications, clinical complications, or outcome. Mechanisms and sources of release of nickel into the serum of patients with acute myocardial infarction or unstable angina pectoris are conjectural, but hypernickelemia may be related to the pathogenesis of ischemic myocardial injury.

www.clinchem.org/content/31/4/556.full.pdf

Blood lead below 0.48 micromol/L (10 microg/dL) and mortality among US adults.

Menke A1, Muntner P, Batuman V, Silbergeld EK, Guallar E.

Abstract

Background— Blood lead levels above 0.48 μmol/L (10 μg/dL) in adults have been associated with increased risk of cardiovascular, cancer, and all-cause mortality. The objective of the present study was to determine the association between blood lead levels below 0.48 μmol/L and mortality in the general US population.

Methods and Results— Blood leadlead-1565598-640x480 levels were measured in a nationally representative sample of 13 946 adult participants of the Third National Health and Nutrition Examination Survey recruited in 1988 to 1994 and followed up for up to 12 years for all-cause and cause-specific mortality. The geometric mean blood lead level in study participants was 0.12 μmol/L (2.58 μg/dL). After multivariate adjustment, the hazard ratios (95% CI) for comparisons of participants in the highest tertile of blood lead (≥0.17 μmol/L [≥3.62 μg/dL]) with those in the lowest tertile (<0.09 μmol/L [<1.94 μg/dL]) were 1.25 (1.04 to 1.51; Ptrend across tertiles=0.002) for all-cause mortality and 1.55 (1.08 to 2.24; Ptrend across tertiles=0.003) for cardiovascular mortality. Blood lead level was significantly associated with both myocardial infarction and stroke mortality, and the association was evident at levels >0.10 μmol/L (≥2 μg/dL). There was no association between blood lead and cancer mortality in this range of exposure.

Conclusions— The association between blood lead levels and increased all-cause and cardiovascular mortality was observed at substantially lower blood lead levels than previously reported. Despite the marked decrease in blood lead levels over the past 3 decades, environmental lead exposures remain a significant determinant of cardiovascular mortality in the general population, constituting a major public health problem.

http://circ.ahajournals.org/content/114/13/1388.long

Depression of cholesterol levels in human plasma following ethylenediamine tetracetate and hydralazine

H. Mitchell Perry Jr., M.D.
Henry A. Schroeder, M.D.
blood-test-1545982-639x493

Abstract

Twenty-two patients received from 3 to 27 Gm. of intravenous EDTA. Six times after an average total dose of 18 Gm., and without change in other metal binding drugs, the total fasting plasma cholesterol fell an average of 75 mg. per 100 ml. of plasma. Initially low values were altered less. The average depression in 112 unselected hypertensive patients was 29 mg. following oral hydralazine therapy; however, among the 66 with high control levels the fall was 48.2 mg. in the first six months, and thereafter 43.5 mg. per 100 ml. of plasma. In 10 hypertensive patients who received an average of 13 Gm. of EDTA the blood pressure decreased an equivocal Math Eq. Hg, although for 6 who took autonomic-blocking agents there was a simultaneous reduction of 34 per cent in the requirement for that drug. Of 9 patients who received single doses of 4 Gm. or more of EDTA, 8 quickly developed fever, and in 2 who received large total doses in relation to their body weight, mucocutaneous lesions were observed.

Full PDF available for purchase: http://www.jclinepi.com/article/0021-9681%2855%2990151-X/abstract

Disappearance of immune deposits with EDTA chelation therapy in a case of IgA nephropathy

by Lin JL, Lim PS

Abstract

In this report, we describe the development of renal function impairment in a 33-year-old patient with mesangial IgA nephropathy and a history of recent gout. Increased body lead burden was identified with a positive EDTA mobilization test. The patient was treated with 1 g of edetate disodium calcium weekly for 2 months until normalization of urinary lead excretion. Improvement of renal function and proteinuria were noted. It was even more interesting to find that both immunofluorescence and electron microscopy studies of the second bioarteriography-1562063-640x600psy specimen revealed the loss of previous mesangial immune deposits. Our case demonstrated that lead may be a nonspecifically damaging factor related to the deterioration of renal function in patients with preexisting renal disease. Moreover, the disappearance of mesangial immune deposits after chelation therapy has not been previously documented. The pathogenetic basis of this observation is unknown, and its causal relationship with lead requires further elucidation.

http://www.ncbi.nlm.nih.gov/pubmed/1292346