Delta-aminolevulinic Acid Levels Research Articles

Neurofilament light chain as a biomarker for acute hepatic porphyrias.

Acute hepatic porphyrias (AHP) represent a rare group of inherited metabolic disorders of heme biosynthesis pathway. This study aims to determine the diagnostic and prognostic value of serum neurofilament light chain (NfL) as potential biomarker for AHP. We conducted a cross-sectional observational study to evaluate NfL levels in patients with AHP. They were divided in different groups: normal health individuals; patients with definitive diagnosis of AHP during acute episodes; patients with AHP and infrequent attacks; patients with AHP and recurrent attacks; asymptomatic individuals with positive genetic testing and urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels elevated 4 or more times ("high excretors"); asymptomatic individuals with exclusive positive genetic test; control group with Hereditary Amyloidosis related to Transthyretin with Polyneuropathy (ATTRv-PN). During acute attacks, serum NfL levels were 68 times higher compared to normal controls and disclosed a strong correlation with ALA and PBG levels; also exhibited elevated levels in patients with chronic symptoms regardless of the number of disease attacks compared to healthy controls, and at similar levels to patients with ATTRv-PN, which is a model of progressive neuropathy. This study represents the first to establish NfL as a biomarker for AHP, disclosing NfL as a sensitive biomarker for axonal damage and chronic symptom occurrence. This study not only underscores that neurological damage associated with the disease in any patient, irrespective of the number of attacks, but also reinforces the progressive and profoundly debilitating nature of acute and chronic symptoms observed in individuals with AHP.

A randomized, placebo-controlled study of givosiran in patients with acute hepatic porphyrias (ENVISION): Final (36-month) analysis of the Taiwan Cohort

Background/purposeAcute hepatic porphyrias (AHP) are rare genetic disorders associated with acute neurovisceral attacks and chronic symptoms. This analysis was conducted to examine the long-term efficacy and safety of givosiran in Taiwanese participants in the ENVISION study (NCT03338816). MethodsPatients (age ≥12 years) with AHP and recurrent attacks were randomized to receive givosiran 2.5 mg/kg or placebo for 6 months during the double-blind period. Patients then switched from placebo to givosiran (placebo crossover group) or continued taking givosiran (continuous givosiran group) during a 30-month open-label extension period. The total study duration was 36 months. An analysis was conducted that included patients enrolled in Taiwan (N = 7). ResultsDuring the double-blind period and open-label extension period, the median annualized attack rates were 0.0 and 0.0, respectively, in the continuous givosiran group (n = 5) and 15.1 and 4.6, respectively, in the placebo crossover group (n = 2; 70 % decrease). Median annualized days of hemin use in the double-blind period and open-label extension period were 0.0 and 0.0, respectively, in the continuous givosiran group, and 23.8 and 5.0, respectively, in the placebo crossover group (79 % decrease). EQ-5D VAS scores remained relatively stable in both groups, and PPEQ responses indicated improved functioning and satisfaction in both groups. Delta-aminolevulinic acid and porphobilinogen levels remained low with long-term givosiran treatment. Serious adverse events were reported by 3 patients (43 %). ConclusionLong-term efficacy and safety results in the Taiwan cohort are consistent with those in the global cohort.

Efficacy and safety of givosiran for acute hepatic porphyria: Final results of the randomized phase III ENVISION trial

Acute hepatic porphyria (AHP) is caused by defects in hepatic heme biosynthesis, leading to disabling acute neurovisceral attacks and chronic symptoms. In ENVISION (NCT03338816), givosiran treatment for 6 months reduced attacks and other disease manifestations, compared with placebo. Here we report data from the 36-month final analysis of ENVISION. Ninety-four patients with AHP (age ≥12 years) and recurrent attacks were randomized 1:1 to monthly double-blind subcutaneous givosiran 2.5mg/kg (N=48) or placebo (N=46) for 6 months. In the open-label extension (OLE) period, 93 patients received givosiran 2.5 or 1.25mg/kg for 6 months or more before transitioning to 2.5mg/kg. Endpoints were exploratory unless otherwise noted. During givosiran treatment, median annualized attack rate (AAR) was 0.4. Through Month 36, annualized days of hemin use remained low in the continuous givosiran group (median, 0.0 to 0.4) and decreased in the placebo crossover group (16.2 to 0.4). At end of OLE, in the continuous givosiran and placebo crossover groups, 86% and 92%, respectively, had 0 attacks. AAR was lower than historical AAR in 98% and 100%, respectively (post hoc analysis), and there were 0 days of hemin use in 88% and 90%, respectively. The 12-item Short Form Health Survey physical and mental component scores increased by 8.6 and 8.1, respectively (continuous givosiran) and 9.4 and 3.2, respectively (placebo crossover). EQ-5D health-related questionnaire scores increased by 18.9 (continuous givosiran) and 9.9 (placebo crossover). Lowering of urinary delta-aminolevulinic acid and porphobilinogen levels was sustained. Safety findings demonstrated a continued positive risk/benefit profile for givosiran. Long-term monthly givosiran treatment provides sustained and continued improvement in clinical manifestations of AHP. Acute hepatic porphyria (AHP) is a group of rare, chronic, multisystem disorders associated with overproduction and accumulation of neurotoxic heme intermediates (delta-aminolevulinic acid [ALA] and porphobilinogen [PBG]), sometimes resulting in recurrent acute attacks and long-term complications. Givosiran, a small interfering RNA that prevents accumulation of ALA and PBG, is approved for the treatment of AHP. These final 36-month results of ENVISION, a phase 3 study of givosiran in patients with AHP and recurrent attacks, show that long-term monthly treatment with givosiran leads to continuous and sustained reductions in annualized attack rate and use of hemin over time, as well as improved quality of life, with an acceptable safety profile. These results are important to physicians, patients, families, and caregivers who are grappling with this debilitating and potentially life-threatening disease with few effective and tolerable treatment options. NCT03338816.

Estimation of urinary delta aminolevulinic acid levels in gasoline and petrol pump workers as an index of lead exposure

Lead poisoning is a phenomenon which with growing globalization is being a subject of worry.ALA i.e Amino levulinic acid is a precursor of hemoglobin, which is synthesized in mitochondria by two main components succinyl Co-A and glycine in presence of ALA-S i.e. amino levulinic acid-synthase. Urinary ALA (ALA-U) has been a recommended biomarker for lead exposure. Inhibition of Amino levulinic acid-dehydratase (ALA-D) results into activation of ALA-S which further synthesizes ALA, excess of ALA is accumulated in the blood, plasma, urine. Present manuscript is focused on the estimation of levels of ALA in the urine of gasoline and pertol pump workers, by acidifying the urine to extract out ALA and reading it colorimetrically as they are exposed to fumes released by gasoline, petrol, and petroleum products which contains lead. Awareness and safety measures such as protective masks and gears should be provided by the respective organisations to the workers.

Estimation of Urinary Delta Aminolevulinic Acid Levels in Females of Reproductive Age as an Index of Lead Exposure

Lead is a toxic heavy metal whose widespread use has caused extensive environmental contamination and health problems particularly in children and women of reproductive age. It affects multiple body systems, including the neurologic, hematologic, gastrointestinal, cardiovascular, and renal systems. Recent studies have shown that lead, has the potential to harm not only the young and the occupationally-exposed, but also older people and females with in the reproductive age. They may have been exposed to lead while working in unregulated occupations, or they may have encountered more lead in the environment on a daily basis. The Aim of the present study is to estimate urinary δ-ALA levels in heterogenous population of females in the reproductive age as an index of lead exposure. This cross- sectional study was conducted on randomly chosen 80 females of reproductive age from different areas of Mumbai with brief history related lead exposure. The morning first mid stream urine samples were collected with all standard precautions and analyzed for δ-ALA using modified Ehrlich’s reagent method. Out of the 80 samples – 69 samples (86.25%) urinary δ-ALA had levels above reference level i.e. (< 5mg/l). This is alarming. The reasons for this exposure may vary and we could not find a single cause for such a high level exposure, but we can say that it is closely related to the duration of exposure. Hence it is to conclude that it is difficult to stop lead exposure completely but by taking necessary precautions and providing health education we can reduce the lead exposure and its ill effects on health.

Study of Estimation of Urinary Delta Aminolevulinic Acid Levels as an Indicator of Lead Exposure in Pottery Workers

Background: Lead toxicity is a significant environmental hazard and has widespread ill effects on human body. In this study we detected the lead exposure by measuring urinary delta aminolevulinic acid levels. The activity of delta aminolevulinic acid dehydratase enzyme is inhibited significantly by lead, which leads to an increase in urinary δ- ALA excretion. Hence we can use estimation of urinary δ-ALA levels as a surrogate marker of lead exposure in pottery workers.
 Aim: To estimate the urinary delta aminolevulinic acid levels in pottery workers as an index of lead exposure.
 Materials and Methods: The study was done on 85 pottery workers of age group between 18 to 50 years with their brief history related to lead exposure. Their urine samples were analysed for δ-ALA by Ehrlich method.
 Results: According to our observation, it was found that out of 85 urine samples; 58 samples showed increased urinary δ-ALA levels (68.23%).
 Conclusion: We conclude that the prevalence of lead exposure in pottery workers in Mumbai is very high. Good hygienic practices and necessary precautions should be followed to avoid its ill effects on human body.

Hyperhomocysteinemia in patients with acute porphyrias: A potentially dangerous metabolic crossroad?

BackgroundAcute porphyrias (AP) are characterized by heme deficiency and induction of hepatic 5-aminolevulinate synthase (ALAS1). Hyperhomocysteinemia (HHcy) is associated with endothelial damage, neurotoxicity and increased risk for vascular diseases. Interestingly, both heme biosynthesis and sulphur amino acid metabolism require vitamin B6, (Pyridoxal-phosphate, PLP) an important cofactor of ALAS1 and of cystathionine β-synthase (CBS) and cystathionine γ-lyase (CGL) enzymes that catabolize homocysteine (Hcy). Moreover, heme itself is an important cofactor for CBS. Aimto assess plasma Hcy status and HHcy main determinants in patients with AP. Materials and methodsA total of 46 patients with AP (31 with Acute Intermittent Porphyria,15 with Variegate Porphyria) were assessed for clinical status (symptomatic vs. asymptomatic), serum Hcy, Cysteine (Cys), Vit.B6, Vit.B12, red blood cell folates and urinary delta-aminolevulinic acid (ALA) and porphobilinogen(PBG) levels (mean of six measurements). ResultsSymptomatic AP patients had significantly higher urinary ALA and PBG levels, plasma Hcy, HHcy prevalence and Hcy/Cys ratio when compared to asymptomatic carriers of AP. Even though no significant correlation was observed between ALA/PBG urinary levels and serum Hcy levels, patients with higher levels of ALA and PBG had significantly higher levels of Hcy, a higher prevalence of moderate-to severe HHcy and serum PLP levels below the 25th percentile of a reference assessment with 300 healthy Italian subjects(<45nmol/L). ConclusionsMost patients with symptomatic AP present HHcy resulting from alterations in sulphur amino acid metabolism. HHcy may represent an indirect marker of ALAS1 induction and its prevalence may be suggestive of a role of HHcy in the pathogenesis and/or comorbidities of AP.

Estimation of Urinary Delta Aminolevulinic Acid (δ-ALA) Levels in Students of Age Group 15 to 25 Years as an Index of Lead Exposure

Background: Lead poisoning is a serious and sometimes fatal condition. It occurs when lead builds up in the body. Students exposed to lead by eating junk foods wrapped in newspaper, the licking of fingers for turning the photocopies, book pages, printout etc. and use of same fingers for eating purpose. Additionally young population get exposed to lead by use of Kohl or Kajal eyeliners, some traditional ethnic medicines, time spent at firing ranges and some hobbies like wall paintings or jobs related to plumbing and soldering. Damage caused by lead poisoning cannot be reversed. Lead inhibits necessary enzymes required for heme synthesis, and this result in increased levels of delta-aminolevulinic acid (δ-ALA) excretion through urine.&#x0D; Aim: To Estimate the urinary δ-ALA levels in the students of age group 15 to 25 years as an index of lead exposure.&#x0D; Study Design: This is a cross-sectional study in Mumbai from a suburban locality.&#x0D; Methodology: The study was done on 70 students of age group between 15 years and 25 years with their brief history related to lead exposure. Their urine samples were analyzed for δ-ALA by using Ehrlich reagent.&#x0D; Results: According to our observation, out of 70 students 46 student’s (65.71%)urine samples shown δ-ALA level above reference level and remaining 24 (34.28%) were considered as below reference level.&#x0D; Conclusion: The prevalence of lead exposure among our study population is 65.71%.&#x0D; Clinical Significance: We conclude that there is high prevalence of lead exposure in students of age group 15 to 25 years in Mumbai and necessary precautions need to be taken to avoid detrimental effects of lead poisoning.

Porfirias agudas: manifestaciones inespecíficas y manejo terapéutico específico

Revisión clínica, científica, teórica y documental teniendo como objetivo principal realizar una revisión sobre la porfiria aguda, su enfoque, diagnóstico y tratamiento. Se utilizó una metodología descriptiva, cualitativa y teórica que permitió la revisión bibliográfica de los estudios relacionados con la porfiria aguda, trastorno congénito poco frecuente que causa alteraciones en las enzimas de la biosíntesis del grupo hem. La importancia de esta patología radica en que se confunde con otras enfermedades debido al cuadro clínico complejo difícil de identificar, lo que ocasiona un diagnóstico tardío que puede comprometer la vida del paciente y por ello se conoce como enfermedad silenciosa. Como conclusión se recomienda mayor atención a los factores precipitantes de los ataques agudos por la elevada morbimortalidad, así como hacer un diagnóstico rápido y oportuno por medios cualitativos y cuantitativos solicitando PBG (porfobilinógeno) y ALA (ácido delta aminolevulínico).

Occupational risk assessment of oxidative stress and genotoxicity in workers exposed to paints during a working week

Paints are complex mixtures of solvents and metals that can induce health damages in workers exposed to them. The aim of the present work was to evaluate possible oxidative and genotoxic effects in workers exposed to paints. Peripheral blood and buccal cell samples were collected from 33 workers exposed to paints and 29 non-exposed workers (controls) during an ordinary working week (Monday morning and Friday evening). Oxidative markers were assessed using thiobarbituric acid assay, carbonylated proteins, superoxide dismutase and catalase activities. Hippuric acid and delta-aminolevulinic acid were determined as biomarkers of toluene and lead exposure, respectively. Genotoxicity was measured through comet assay and micronucleus (MN) frequencies. The exposed group showed higher hippuric acid and delta-aminolevulinic acid levels (Friday samples) and lower superoxide dismutase activity (Monday samples) in relation to control group. DNA damage index (comet assay) was higher in the exposed group, both in Monday and Friday samples, compared to the control group. No differences were observed in frequency of micronuclei (MN) between the groups, either in lymphocytes or buccal cells. However, the exposed group presented an increase (Monday samples) in nuclear buds frequency in lymphocytes - a marker of gene amplification - as well as an increase in condensed chromatin in the buccal cells (Monday and Friday samples), suggesting induction of apoptosis. Furthermore, a decrease in the nuclear division index (Friday samples) was observed in the exposed group, indicating that paint exposure induces cytostatic effects in lymphocytes. The results suggest that individuals exposed to paints have increased levels of DNA damage.

Evaluation of delta-aminolevulinic acid levels in the urine of Angooran Lead & Zinc Company staff

Currently, attention has shifted to chronic or subclinical disorders attributed to lead (Pb) exposure. The aim of this study was to determine delta-aminolevulinic acid (δ-ALA) levels in urine of Angooran Lead & Zinc Company workers. This cross-sectional study was conducted on 170 workers, in which 24 h urinary samples were collected and δ-ALA levels were measured spectrophotometrically. Questionnaire forms were completed indicating age, location, and duration of work. The mean δ-ALA level in urine was 5.44 mg L−1. δ-ALA levels were correlated with age, location, and duration of work in the company. The mean δ-ALA level in the urine of workers was in the upper limit of normal ranges. δ-ALA level in urine may not be the best discriminating factor of Pb exposure from the baseline to the high levels, but is recommended as a regular and routine test for all Pb-exposed workers in addition to the measurement of Pb in blood for subjects with higher δ-ALA levels.

Environmental lead exposure and its relationship to traffic density among Senegalese children: a cross-sectional study

Leaded-gasoline is probably the primary source of lead (Pb) exposure in Dakar (Senegal). The present cross-sectional study was undertaken to investigate the levels of Pb in Senegalese children and to present helpful data on the relationship between Pb levels and changes in biological markers of heme biosynthesis and oxidative stress. A total of 330 children, living since birth either in rural or urban areas (ie, Khombole (n = 162) and Dakar (n = 168), respectively) were included. During this cross-sectional study, the mean blood (B)-Pb level in all children was 7.32 +/- 5.33 microg/dL, and was influenced by the area of residence and gender. In rural children, 27 subjects (16.7%), 18 boys (19.6%) and nine girls (12.9%), had a B-Pb level > 10 microg Pb/dL, whereas 99 urban children (58.9%), respectively, 66 boys (71.8%) and 33 girls (43.4%), had alarmingly high B-Pb levels. Accordingly, urine delta-aminolevulinic acid levels were higher in children living in the urban area than in the rural areas (P < 0.001), and closely correlated with the B-Pb levels (P < 0.01). Moreover, glutathione peroxidase (GPx) activity, selenium (Se) level, glutathione reductase (GR) activity, and glutathione status were significantly influenced by area of residence and/or by gender. GPx activity and Se level were not only negatively correlated with B-Pb levels, but also positively correlated together (P < 0.01). Taken together, the present results allow us to conclude that urban children have higher B-Pb levels than rural children, and that of these children, boys have higher B-Pb levels than girls, leading thereby to alterations of heme biosynthesis and pro-oxidant/antioxidant balance. We also suggest that exposure to Pb and the Pb-induced adverse effects merits attention and that the development of preventive actions are of increasing importance in Senegal.

Critical dose of lead affecting delta-aminolevulinic acid levels.

To estimate the critical dose of the association between the blood lead concentration (BPb) and delta-aminolevulinic acid (ALA) levels, ALA levels in plasma (ALA-P), blood (ALA-B), and urine (ALA-U), and the activity of delta-aminolevulinic acid dehydratase (ALAD) were determined in 186 Japanese lead workers, aged 18-62 yr, with BPb levels of 2.1-62.9 g/dl. For this purpose, the benchmark dose (BMD) method, recently used in the environmental health field in place of the no-observed-adverse-effect level, was introduced into this study. The BMD was defined as the BPb level that resulted in an increased probability of abnormal change in ALA-related parameters by an excess risk (BMR) of 5% in exposed workers i.e., from P0 (abnormal probability of 5% in unexposed workers) to P0+BMR for exposed workers at the BMD. ALA-related parameters were significantly correlated with BPb. The BMDs computed from the 186 workers, after controlling for age, were 15.3-20.9 microg/dl for ALA levels, and 2.9 microg/dl for ALAD; likewise, the BMDs from the 154 workers with BPb levels of less than 40 microg/dl were 3.3-8.8 microg/dl for ALA levels, and 2.7 microg/dl for ALAD. Since the cutoff value of ALA-P, computed from the latter workers, seems to be closer to the upper normal limit in unexposed adults than does that from the former workers, it is suggested that the critical dose of BPb causing the increased levels of ALA is below 10 microg/dl. Such critical doses are necessary to promote preventive activities of adverse effects of lead.

Mobilization of lead by calcium versenate and dimercaptosuccinate in the rat.

1. Calcium disodium ethylenediaminetetraacetate (CaNa2 EDTA) and meso-2,3-dimercaptosuccinic acid (DMSA) individually and in permutation-combination in various doses (0.1, 0.2 and 0.4 mmol/kg bodyweight) were investigated for their efficacy to mobilize lead from vital tissues into urine and faeces and to restore the lead-sensitive biochemical parameters in lead pre-exposed rats with a view to develop the most acceptable treatment regimen for lead poisoning with a minimal loss of endogenous essential elements. 2. The combined therapy was more effective than a single chelator treatment. 3. The combination of 0.2 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA caused a lower depletion of zinc, calcium and iron but possessed almost equal capability to that of 0.4 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA to produce urinary as well as faecal excretion of lead, to reduce the tissue burden of lead, including that of the brain, and to reverse lead-induced biochemical alterations. 4. The combination of 0.2 mmol/kg CaNa2EDTA + 0.4 mmol/kg DMSA has shown a definite improvement over previously reported combinations in terms of removal of lead from tissues, particularly the brain, restoration of urinary delta-aminolevulinic acid levels and a decrease in the loss of body zinc and is, therefore, recommended for the treatment of lead intoxication.

Lead exposure among Malaysian school children using δ-aminolevulinic acid as an indicator

A study on lead exposure among school children aged between 7 and 12 years from Kajang and Sepang in the state of Selangor, Malaysia was carried out using delta-aminolevulinic acid (δ-ALA) levels in the urine as an index. The δ-ALA levels in urine were linked to variables which could contribute to lead exposure. Out of 1628 school children studied [Kajang (43.5%) and Sepang (56.5%)], only 194 subjects (16 and 8.8% from Kajang and Sepang, respectively) had urinary δ-ALA levels between 0.6 and 2.0 mg/100 ml. However, χ 2 analysis demonstrated significant association between δ-ALA of this group to some of the variables. The strongest association was found in the habit of biting fingernails ( P < 0.025). Other statistically significant correlations were found between δ-ALA and father's occupation ( P < 0.05) and the amount of time spent playing in the field ( P < 0.01). Generally, this study indicates that school children in Kajang and Sepang are still relatively safe from excessively high lead exposure. However, a more sensitive indicator, which is based on a lower tolerable lead limits, such as lead in blood, are necessary to affirm this finding.

Effects on health of atmospheric lead in roadside exposure in Jakarta

The effects of lead on the health of two Japanese males, ages 26 and 54, both of whom had previously resided in a Japanese city before staying for a period of one month in Jakarta, Republic of Indonesia. The subjects spent four to five days on a roadside in Jakarta where lead levels in the air varied from one to three μg/m(3), while that in Japan was approximately 0.1 μg/m(3). The followings were measured before, during and after the lead exposure: lead in blood, the activity of delta-aminolevulinic acid dehydratase, lead in urine per day and delta-aminolevulinic acid levels in urine per day. Lead in blood, the activity of delta-aminolevulinic acid dehydratase and lead in urine per day showed no marked changes, while delta-aminolevulinic acid levels in urine per day increased significantly after the exposure. Thus, lead and delta-aminolevulinic acid levels in urine per day are recommended as the most sensitive indicators of the short-term effect of lead.

Delta-Aminolevulinic acid in plasma or whole blood as a sensitive indicator of lead effects, and its relation to the other heme-related parameters.

To evaluate the subclinical effect of lead exposure, we determined delta-aminolevulinic acid (ALA) levels in plasma (ALA-P), blood (ALA-B), and urine (ALA-U) and the activity of delta-aminolevulinic acid dehydratase (ALAD) in lead workers. Almost all of the ALA molecules in blood were present in plasma and not in blood cells, irrespective of the blood lead concentration (Pb-B). ALA-P or ALA-B levels increased slowly at Pb-B levels below 40 micrograms/dl (slow phase) and rapidly at levels above 40 micrograms/dl (rapid phase). In both phases, ALA-P and ALA-B were well correlated with Pb-B and ALAD activity. The threshold value (no-effect level) of Pb-B for elevation of the ALA-P or ALA-B level was coincident with that for ALAD inhibition; the value was around 5 micrograms/dl. In the rapid phase, ALA-P increased continuously up to 100 micrograms/dl of Pb-B, while ALAD activity reached a plateau. Receiver operative characteristic (ROC) plot analyses indicated that ALA-P and ALAD activity [ALAD(u)] had a similar diagnostic value at Pb-B levels between 10 and 40 micrograms/dl, although ALAD(%), the remaining ALAD activity as a percentage of the whole activity restored by zinc and dithiothreitol, had the most powerful diagnostic efficiency at these Pb-B levels. By contrast, ALA-U and zinc protoporphyrin were less effective for the diagnosis of lead exposure than ALAD and ALA-P. These findings indicate that ALA-P is the best discriminators of lead exposure form baseline to high levels of exposure.

Efficacy of combined chelation in lead intoxication.

The combination of a bone lead mobilizer, viz., CaNa2EDTA, and a soft tissue depleter such as meso-2,3-dimercaptosuccinic acid (DMSA) or the sodium salt of 2,3-dimercapto-1-propane-sulfonic acid (DMPS) was investigated for its efficacy to enhance the excretion of lead, to reduce its body burden, and to reverse certain lead-induced biochemical alterations by either of them alone in rats. The administration of CaNa2EDTA or DMSA was more effective than that of DMPS, and the combination of CaNa2EDTA and DMSA was more efficient than that of CaNa2EDTA and DMPS or the individual chelators in enhancing urinary/fecal excretion of lead, in reducing hepatic, renal, and femur concentration of lead, and in restoring lead-induced inhibition of blood delta-aminolevulinic acid dehydratase and increase in blood zinc protoporphyrin and urinary delta-aminolevulinic acid levels. The brain lead was depleted by DMSA only, but the combined chelation failed to improve upon the ability of DMSA. However, chelation therapy increased diuresis and tissue depletion of zinc.

Medical examination of workers exposed to lead in the Philippines

The medical examination of workers exposed to lead was conducted as part of the activity of the Occupational Safety and Health Center (OSHC) Project in the Philippines (JICA Project). The subjects of the medical examination were 21 male and 193 female workers of a semi-conductor plant (abbreviated A company), 59 male and 6 female workers of a refrigerator manufacture (B company); 199 male workers of a storage battery manufacturer (C company); and 107 male and 6 female workers of a lead smelter (D company). Among the examination items were questions regarding occupational history, subjective complaints and objective signs, determination of blood lead levels, urine delta aminolevulinic acid levels, and examination for anemia. The survey was conducted from June to September in 1990. The following results were obtained: 1) The mean age of the workers ranged from 21.8 to 33.8 years. Those of companies A and B were younger than those of companies C and D. The mean employment duration of males at C company was 10.7 yr, and the longest among the four companies. That in both sexes for A company was 1.8 yr and the shortest among the above mentioned companies. 2) The blood lead geometric mean levels of companies C and D showed the highest concentration. The level in males of C company was 64.5 micrograms/dl and that of D company was 80.8 micrograms/dl. The level in females of A company was 9.9 micrograms/dl and the lowest in concentration. The urine delta aminolevulinic acid geometric mean levels were less than 6.0 mg/l in the four companies. There was no company having hemoglobin mean values less than 14.0 g/dl in males or less than 12.0 g/dl in females. 3) The proportion of blood lead levels of 60 micrograms/dl or more was 67.3% in males of C company, and 89.7% in males and 16.7% in females of D company. The proportion of urine delta aminolevulinic acid levels of 6 mg/l or more was 1.0% in females of A company, 20.1% in males of C company, and 43.0% in males of D company. The proportion of hemoglobin values less than 14.0 g/dl in males or less than 12.0 g/dl in females was 4.7% in females of A company, 1.7% in males of B company, 3.5% in males of C company, and 12.1% in males of D company.(ABSTRACT TRUNCATED AT 400 WORDS)

Alterations in tissue Pb distribution and hematopoietic indices during advanced age

The inevitable degenerative processes accompanying advanced age suggest that senescent organisms might exhibit differences in toxicokinetics or an altered manifestation of toxic effects. This hypothesis was tested in the present experiment which compared tissue distribution and hematopoietic indices in groups of adult (8 months) and old male Fischer-344 rats (16 months) exposed to concentrations of 0, 250 or 500 ppm lead (Pb) acetate in drinking water for 7 months. A group of young (weanling) rats was included as a partial comparison. Blood lead (PbB), zinc protoporphyrin (ZPP) and urinary delta-aminolevulinic acid levels were determined after both 3 and 7 months of exposure. Organ weights, tissue Pb concentrations and urinary excretion of Pb, calcium, copper, and zinc were examined after 7 months of exposure. Tissue Pb distribution was markedly altered in old rats: bone and kidney Pb were reduced; liver Pb was substantially increased, even though PbB levels in adult and old rats were comparable at both measurement intervals, as was urinary Pb excretion at 7 months. Pb-induced elevation of ZPPs exhibited differential changes between 3 and 7 months: values in adults declined while levels in old rats increased or remained unchanged. These findings show that the responses of adult rats to Pb do not predict those of older rats and indicate the need for further characterization and elaboration of mechanisms of toxic effects with advanced age.