Environmental lead exposure and activity of delta-aminolevulinic acid dehydratase (ALA-D) in maternal and cord blood.

The hypothesis that environmental lead exposure measured from blood (Pb-B) inhibits delta-aminolevulinic acid dehydratase activity (ALA-D) from whole blood was tested in 241 urban mothers and their newborns. Geometric means and (5th and 95th Percentiles) for maternal and cord Pb-B were 6.4 microg dl(-1) (3.4-11.9) and 4.6 microg dl(-1) (2.8-9.2). Spearman correlations between mother and cord Pb-B and ALA-D were all negative but statistically significant only for cord Pb-B and mother ALA-D. A potential lead threshold, was identified between 3.2 and 4.8 microg dl(-1), above which ALA-D may be inhibited by lead, and below which ALA-D may be insensitive or even activated. In conclusion, low environmental exposure to lead is responsible for a demonstrable biochemical effect. This potential ALA-D inhibition may lead to neurotoxic effects, especially in newborns who have high level of neurogenesis.     

Effect of lead on the levels of some immunoregulatory cytokines in occupationally exposed workers

Lead (Pb) may affect humoral and cellular immunity, acting on lymphocytes as well as on granulocytes and monocytes. Cytokines and nitric oxide (NO) play a central role in the immune balance. In this study, plasma levels of nitrites and nitrates (NOx), IL2, IL4, IL6, IL10, TNF-alpha and INF-gamma, were measured in healthy workers with very low (Pb-B=3.2-18.0 microg/dL) and low (Pb-B=9.1-46.0 microg/dL) Pb-exposure compared to non-exposed workers. Low Pb-exposed workers (Pb-B=9.1 -46.0 microg/ dL) were found to have significantly higher plasma IL-10 levels, and tendentially higher plasma TNF-alpha levels compared to non-exposed workers. This is the first report of a significant increase of plasma IL-10 levels in Pb-exposed workers. Plasma IL-10 increase was influenced by blood Pb levels even after correction for main confounding factors. No difference was found in plasma NOx levels between Pb-exposed and non-exposed workers, which is in agreement with previous findings exclusively regarding groups in the general population. Low Pb-exposure can induce an increase of pro-inflammatory cytokines, such as TNF-alpha, with a consequent increase of other cytokines, such as IL-10, considered a T cell cross-regulatory factor, suggesting possible interference of Pb in the system of immunophlogosis.     

Tumour necrosis factor-alpha levels in aqueous humour and serum from patients with uveitis: the involvement of HLA-B27

OBJECTIVE: To study the local and systemic levels of the tumour necrosis factor-alpha in patients with active uveitis and to determine the implication of TNF-alpha in rheumatological uveitis and to observe if this relationship is more significant in the B27 positive patients. PATIENTS AND METHODS: Patients were selected on the basis of a diagnosis of uveitis of any aetiology. Data from 23 patients were stratified into two categories according to the presence or absence of systemic rheumatic disease. The first group comprised nine patients with rheumatic disease; the second group contained 14 patients without rheumatic disease. The patients were also sub-classified into those who were HLA-B27 positive (14 patients) and those who were not. TNF-alpha levels in serum and aqueous humour from a group of 16 patients with uncomplicated cataracts were analysed as a control group. RESULTS: In the control group (n = 16) the serum TNF-alpha concentration was 13.1 +/- 2.9 pg/ml and the aqueous humour concentration of TNF-alpha was 0.56 +/- 1.53 pg/ml. In uveitis patients (n = 23) the serum TNF-alpha concentration was 35.35 +/- 26.77 pg/ml and the aqueous humour concentration of TNF-alpha was 15.1 +/- 1.70 pg/ml (p < 0.01). In HLA-B27 positive patients (n = 9) the serum TNF-alpha concentration was 45.56 +/- 34.17 pg/ml and the aqueous humour concentration of TNF-alpha was 15.89 +/- 0.93 pg/ml. In HLA-B27 negative patients (n = 14) the serum TNF-alpha concentration was 28.79 +/- 19.38 pg/ml and aqueous humour concentration of TNF-alpha was 14.57 +/- 1.91 pg/ml (p < 0.01). CONCLUSIONS: The concentration of TNF-alpha in aqueous humour in patients who are HLA-B27 positive is significantly greater than in those who are B27 negative. No significant differences in the concentrations of TNF-alpha in serum or aqueous humour in patients with or without rheumatic diseases were detected. TNF-alpha is a cytokine that may participate actively in the pathogenesis of clinical uveitis.     

Effects of low mercury vapour exposure on the thyroid function in chloralkali workers

Forty-seven chloralkali workers exposed to mercury vapour for an average of 13.3 years were compared with 47 referents matched for age in a cross-sectional study of thyroid function. The mean urinary mercury concentration in the exposed workers was low compared with other studies of chloralkali workers: 5.9 nmol mmol-1 creatinine (range 1.1-16.8) vs 1.3 nmol mmol-1 creatinine (range 0.2-5.0) in the reference group. The median serum concentration of reverse triiodothyronine (rT3) was statistically significantly higher in the exposed subjects compared with the referents (268 pmol l (-1) and range 161-422 vs 240 pmol l(-1) and range 129-352; P = 0.009). The difference between the exposed subjects and the referents was most pronounced in the highest exposed sub-groups. The free thyroxine (T4)/free T3 ratio was also higher in the highest exposed subgroups compared with the referents. The median serum concentration of tumour necrosis factor alpha (TNF-alpha) was lower in the exposed subjects (7.3 pg ml(-1) and range 4.4-69.7 vs 8.0 pg ml(-1) and range 6.0-34.6; P = 0.004). Exposed subjects with the lowest urinary iodine (<67.8 nmol mmol(-1) Cr) had higher serum concentrations of reverse T 3 and a higher free T4/free T3 ratio than the other subjects, suggesting that a low concentration of iodine in urine may be a risk factor for increased serum concentrations of reverse T3 and the free T4/free T3 ratio in subjects exposed occupationally to mercury vapour. The study could indicate a slight effect of low mercury vapour exposure on the function of the enzyme type I iodothyronine deiodinase, possibly modified by comparatively low urinary iodine concentrations.     

Serum immunoglobulins and lymphocyte subset distributions in children and adults living in communities assessed for lead and cadmium exposure

This study assessed the impact of environmental cadmium and lead exposure on the immune system of more than 2000 children and adults. Serum immunoglobulins [immunoglobulins (Ig) A, G, and M] and peripheral blood lymphocyte phenotypes (T cells, B cells, NK cells, and CD4/CD8 subsets) were measured in a total of 2041 children and adults who lived either in sites with elevated soil levels of cadmium and lead (n = 1561) or in comparison communities (n = 480). The blood lead and urine cadmium levels of participants were somewhat higher than national averages. Mean blood lead levels were 7 microg/dl for participants aged 6-35 mo; 6 microg/dl for participants aged 36-71 mo, 4 microg/dl for participants aged 6-15 yr; and 4.3 microg/dl for participants aged 16-75 yr. Multivariate analysis indicated no marked differences in any of the immune marker distributions attributed to lead for adults or children over 3 yr of age. However, in children under age 3, increased blood lead levels, principally those over 15 microg/dl, were associated with increases in IgA, IgG, IgM, and circulating B lymphocytes. Among adults, urine cadmium levels over 1.5 microg/g were associated with higher levels of IgA and circulating B lymphocytes. No evidence of immunosuppression was noted. The findings of potential immunologic effects at lead levels > 15 microg/dl in young children and at urine cadmium levels > 1.5 microg/g in adults are interesting, but too few participants had these high levels to delineate a threshold. Therefore, we find these results intriguing, but requiring confirmation in populations with higher exposure levels.     

Naphazoline-induced neuroendocrine changes: increases in ANP and cGMP levels,but suppression of NE, 3H-NE,and cAMP levels in rabbit eyes

The objective of this study was to determine whether naphazoline, an alpha 2 (alpha2)/imidazoline (I1) agonist, can alter endogenous levels of atrial natriuretic peptide (ANP) and norepinephrine (NE) in aqueous humor and cyclic nucleotide (cAMP, cGMP) accumulation and NE overflow in the iris-ciliary body (ICB) of the rabbit eye. Topical naphazoline (25, 75, and 250 microg) caused a dose-dependent elevation of the ANP levels (36, 54, and 137 pg/ml, respectively) in aqueous humor. This effect was antagonized by pretreatment with efaroxan, an antagonist of I1/alpha2 receptors. Another alpha2/I1 agonist, moxonidine (75 microg topically), caused significant increases in ANP levels in aqueous humor, whereas other relatively selective alpha2-adrenergic receptor agonists, brimonidine (50 microg topically) and oxymetazoline (75 microg topically), did not. In naphazoline (75 microg) pretreated eyes, the NE levels in aqueous humor were attenuated by 36% (from 6.0 to 3.8 pg/ml). Furthermore, naphazoline (1, 10, and 100 micromol/l) caused a dose-related inhibition of NE release from ICBs: 25, 45, and 80%, respectively. The isoproterenol (1 micromol/l) stimulated cAMP accumulation was inhibited 53% by naphazoline (100 micromol/l). In contrast, naphazoline significantly increased the cGMP levels in ICBs. These data demonstrate that naphazoline acts on I1 receptors to increase ANP and to reduce NE levels in aqueous humor. The former effect could also contribute to elevation of cGMP levels and inhibition of cAMP accumulation in the ICB. Further studies will be required to determine if elevation of ANP levels is a critical component of naphazoline-induced alteration of aqueous humor dynamics.     

Atorvastatin effect on circulating and leukocyte-produced CD40 ligand concentrations in people with normal cholesterol levels: a pilot study

STUDY OBJECTIVES: To investigate whether atorvastatin decreases serum or leukocyte-produced CD40 ligand (CD40L) levels and whether these effects are dependent on reduction in low-density lipoprotein cholesterol (LDL) levels in people without overt dyslipidemia. DESIGN: Prospective pilot study. SETTING: University research center. SUBJECTS: Twenty-five normocholesterolemic volunteers (mean age 32 +/- 11 yrs; 15 women, 10 men) without cardiovascular disease. INTERVENTION: After a 2-week drug-free run-in period, subjects received atorvastatin 80 mg/day orally for 16 weeks. MEASUREMENTS AND MAIN RESULTS: All lipoprotein level measurements were performed with the subject in the fasting state. The CD40L concentrations were measured by immunofluorescence detection in serum and leukocyte culture supernates after 24-hour incubation, and treatment effect was analyzed. Baseline mean +/- SD total cholesterol, LDL, high-density lipoprotein cholesterol, and triglyceride levels were 179 +/- 33, 97 +/- 29, 62 +/- 20, and 102 +/- 69 mg/dl, respectively. Mean changes in each of these levels, respectively, after 16 weeks of atorvastatin were -34%, -59%, +3%, and -23%. The median serum CD40L level was lower at 16 weeks (2.3 ng/ml, interquartile range [IQR] 1.2-5.0 ng/ml) than at baseline (3.0 ng/ml, IQR 2.1-3.7 ng/ml), but the change was not significant (p=0.24). However, atorvastatin significantly lowered CD40L produced from leukocytes by 57% (21 pg/mg of protein [IQR 10-38 pg/mg] vs 49 pg/mg [IQR 21-149 pg/mg], p=0.045). Effects were independent of reduction in cholesterol levels. CONCLUSION: Although atorvastatin did not significantly lower serum CD40L levels, significant reduction in leukocyte production was seen independent of degree of LDL reduction. These pilot data suggest a potential benefit in normocholesterolemic individuals that should be further investigated, and that leukocyte CD40L concentrations should be considered in the drug response.     

Beryllium-stimulated production of tumor necrosis factor-alpha by a mouse hybrid macrophage cell line

Chronic beryllium disease (CBD) results from exposure to the light-weight metal beryllium (Be). In vitro stimulation of bronchoalveolar lavage cells from CBD subjects causes the production of high levels of TNF-alpha, IFN-gamma and IL-6. We tested the hypothesis that Be-stimulation might induce the production of TNF-alpha by macrophage cell lines. We observed that H36.12j cells (12j), a mouse hybrid macrophage cell line, but not other mouse and human macrophage cell lines, produced TNF-alpha upon Be-stimulation. The response was maximal at 100 microM BeSO4 and did not occur when 12j cells were stimulated with either aluminum sulfate or cobalt sulfate. Beryllium-stimulated the production of 725+/-25 pg/ml (mean +/- SEM) TNF-alpha protein by 12j cells as measured by ELISA of culture supernatants after 24 h. As measured by RT-PCR, Be-stimulated 12j cell TNF-alpha protein production was accompanied by an increased intracellular TNF-alpha mRNA at 3 and 24 h. The addition of 10U or 100U of rMu-IFN-gamma to Be-stimulated 12j cells further increased TNF-alpha production 1.5-4 fold (1.6+/-0.1 ng/ml) respectively. Bacterial lipopolysaccharide (LPS, 1 microg/ml) stimulated production of TNF-alpha in 12j culture supernatants after 6 h (515+/-151 pg/ml). This early versus late TNF-alpha production suggests that LPS and Be both stimulate 12j cell TNF-alpha synthesis, but through different pathways. We report for the first time, the direct effects of Be stimulation on the ability of 12j cells to produce TNF-alpha. The 12j cell line, contrasted with other macrophage hybrids that do not respond to Be-stimulation, may provide a useful tool to evaluate the mechanisms by which Be stimulates macrophage cytokine production, and by which T cell derived IFN-gamma amplifies TNF-alpha production in granulomatous diseases.     

Effects of lead on Na(+)-K(+) ATPase and Ca(+2) ATPase activities and lipid peroxidation in blood of workers

Lead is considered one of the major environmental toxicants that causes hematological, neurological, and gastrointestinal dysfunction. In this study, the authors examined the relationship between lead and lipid peroxidation, lead and Na(+)-K(+) ATPase activity, and lead and Ca(+2) ATPase activity in blood of workers. The working group consisted of 30 male workers occupationally exposed to lead at least for 10 years. The control group consisted of 20 healthy male individuals not involved with job-related lead exposures. Blood lead content of the control group and the working group were 10.0 +/- 1.8 microg/dl and 317.3 +/- 47.6 microg/dl, respectively. Malondialdehyde (MDA) value of the working group (0.57 +/- 0.30 nmol MDA/ml) was significantly greater than MDA value of the control goup (0.17 +/- 0.02 nmol MDA/ml). In the working group, both Na(+)-K(+) ATPase activity (105.0 +/- 47.0 nmol Pi. mg protein(-1) x h(-1)) and Ca(+2) ATPase activity (58.0 +/- 40.0 nmol Pi. mg protein(-1) x h(-1)) were lower compared with the corresponding values of Na(+)-K(+) ATPase activity (247.0 +/- 41.0 nmol Pi. mg protein(-1) x h(-1)) and Ca(+2) ATPase activity (230.0 +/- 41.0 nmol Pi. mg protein(-1) x h(-1)) of normal controls. The results show that lead exposure causes inhibition of Na(+)-K(+) ATPase and Ca(+2) ATPase activities and also results in increased lipid peroxidation.     

Serum copper levels among quartz stone crushing workers: a cross sectional study

The present cross sectional study was carried out among 134 workers of quartz stone crushing units to assess the serum Cu activity among quartz stone workers without disease. Demographic and occupational details of the subjects were recorded on the predesigned proforma. Standard diagnostic criteria were used for diagnosing silicosis and tuberculosis. The pulmonary functions of the subjects were measured using Spirovit SP-10. The mean age for male was found to be 26.63 +/- 6.28 years while that for female was 21.93 +/- 4.29 years and for the whole group was 26.13 +/- 6.26 years. In the present study only one case of silicosis and seven cases of tuberculosis were found. The mean serum Cu levels of those having respiratory disease was found to be 91.5 +/- 19.8 microg/dl while mean serum Cu level of those free from respiratory disease was 86.8 +/- 21.3 microg/dl The difference was found to be statistically non-significant (t = 0.64, df= 1, P > 0.05). Thus, in the present study, though the elevated level of serum Cu was found in solitary case of silicosis, no association could be established between the silica exposure and serum copper levels as suggested by non-significant effect of duration of exposure (P = 0.53).     

Pre- and postnatal lead effect on head circumference: a case for critical periods

We examined the association of maternal prenatal [range of median blood lead level 7.5-9.0 microg/dl (0.36-0.43 micromol/l) during pregnancy] and child postnatal blood lead level [range of median blood lead level from birth to 48 months 7.0-10.0 microg/dl (0.34-0.48 micromol/l)] with head circumference in from 119 to 199 children from the Mexico City Prospective Lead Study. We used repeated multiple regression modeling with a standard set of control variables, entering blood lead level last. Using Bonferroni-corrected probability values to control for inflation of Type I error due to multiple testing at each age, we found significant negative associations (p<0.05, two-tailed) between 6-month head circumference and 36-week maternal blood lead level, and 36-month head circumference and 12-month blood lead level. Over the 25-75% interquartile range of measured blood lead, head circumference decreased around 0.4 cm. Over the 1-35 microg/dl (0.05-1.68 micromol/l) range of maternal blood lead at 36 weeks, the estimated reduction in 6-month head circumference was 1.9 cm (95% CI = 0.9-3.0 cm). These results suggest that children are more vulnerable to certain effects of lead exposure at specific age ranges, and that the effect of lead on head circumference only becomes evident for brief periods in the first 4 years of life. We discuss various artifacts as well as possible mechanisms by which lead might have produced the observed pattern of results. We suggest that higher lead exposure prevalent several decades ago might have subtly influenced published normative human growth data.     

Assessment of semen function and lipid peroxidation among lead exposed men

The study population included healthy, fertile men, employees of Zinc and Lead Metalworks (n=63). Workers exposed to lead were divided into two groups: a group with moderate exposure to lead (ME) - blood lead level (PbB) 25-40 microg/dl and a group with high exposure to lead (HE) PbB=40-81 microg/dl. The control group consisted of office workers with no history of occupational exposure to lead. Evaluation of lead, cadmium and zinc level in blood and seminal plasma, zinc protoporphyrin in blood (ZPP), 5-aminolevulinic acid in urine (ALA), malondialdehyde (MDA) in seminal plasma and sperm analysis were performed. No differences were noted in the concentration of cadmium and zinc in blood and seminal plasma in the study population. Lipid peroxidation in seminal plasma, represented as MDA concentration, significantly increased by about 56% in the HE group and the percentage of motile sperm cells after 1 h decreased by about 34% in comparison to the control group. No statistically significant correlation between other parameters of sperm analysis and lead exposure parameters nor between lead, cadmium and zinc concentration in blood and seminal plasma were found. A positive association between lead intoxication parameters (PbB, ZPP, lead seminal plasma) and MDA concentration in sperm plasma and inverse correlation with sperm cells motility (PbB, ZPP) was found. An increased concentration of MDA was accompanied by a drop in sperm cells motility. In conclusion, we report that high exposure to lead causes a decrease of sperm motility in men most likely as a result of increased lipid peroxidation, especially if the level in the blood surpasses the concentration of 40 microg/dl.     

Plasma cholecystokinin and hepatic enzymes, cholesterol and lipoproteins in ammonium perfluorooctanoate production workers

Ammonium perfluorooctanoate is a potent synthetic surfactant used in industrial applications. It rapidly dissociates in biologic media to perfluorooctanoate [CF3(CF2)6CO2-], which is the anion of perfluorooctanoic acid [PFOA, CF3(CF2)6COOH]. PFOA is a peroxisome proliferator known to increase the incidence of hepatic, pancreas and Leydig cell adenomas in rats. The pancreas acinar cell adenomas may be the consequence of a mild but sustained increase of cholecystokinin as a result of hepatic cholestasis. Although no significant clinical hepatic toxicity was observed, PFOA was reported to have modulated hepatic responses to obesity and alcohol consumption among production workers. To further assess these hypotheses, we examined medical surveillance data of male workers involved in ammonium perfluorooctanoate production in 1993 (n=111), 1995 (n=80) and 1997 (n=74). Serum PFOA was measured by high-performance liquid chromatography mass spectrometry methods. Plasma cholecystokinin was measured (only in 1997) by the use of direct radioimmunoassay. Serum biochemical tests included hepatic enzymes, cholesterol and lipoproteins. Serum PFOA levels, by year, were: 1993 (mean 5.0 ppm, SD 12.2, median 1.1 ppm, range 0.0-80.0 ppm); 1995 (mean 6.8 ppm, SD 16.0, median 1.2 ppm, range 0.0-114.1 ppm); and 1997 (mean 6.4 ppm, SD 14.3, median 1.3 ppm, range 0.1-81.3 ppm). Cholecystokinin values (mean 28.5 pg/ml, SD 17.1, median 22.7 pg/ml, range 8.8-86.7 pg/ml) approximated the assay's reference range (up to 80 pg/ml) for a 12 hour fast and were negatively, not positively, associated with employees' serum PFOA levels. Our findings continue to suggest there is no significant clinical hepatic toxicity associated with PFOA levels as measured in this workforce. Unlike a previously reported observation, PFOA did not appear to modulate hepatic responses to either obesity or alcohol consumption. Limitations of these findings include: 1) the cross-sectional design as only 17 subjects were common for the three surveillance years; 2) the voluntary participation that ranged between 50 and 70 percent; and 3) the few subjects with serum levels > or = 10 ppm.     

Pharmacokinetics of all-trans retinoic acid, 13-cis retinoic acid, and fenretinide in plasma and brain of Rat.

We have measured the pharmacokinetics of three retinoids, all-trans retinoic acid, 13-cis retinoic acid, and fenretinide in rat blood and rat brain [especially white matter (WM) and gray matter (GM)] to help select retinoids for treating human malignant glioma. All-trans retinoic acid permeated well into the WM, giving peak concentration in WM of 25.7 microg/g, 6 to 7 times higher than the peak serum concentration. There was less 13-cis retinoic acid in WM: area under the curve (AUC)(0-->infinity) WM/AUC(0-->infinity) serum = 18.00 microg ml(-1) h/32.67 microg ml(-1) h. The ratio WM/GM was over 1 for these two compounds, but the half-lives were short in the serum and cerebral tissue (0.57-1.02 h). Fenretinide had different pharmacokinetics: the peak concentrations were in serum (1.7 microg/ml) and WM (1.2 microg/ml)-low, but the AUC(0-->infinity) was large (25.55 microg ml(-1) in serum and 57.53 microg ml(-1) in WM) due to its long elimination half-life (13.78 h in serum and 17.77 h in WM). These findings provide information that may be used to select a retinoid and establish therapeutic regimens that provide optimal efficacy with minimal toxicity.     

Exposure to Arsenic in urban and rural areas and effects on thyroid hormones

Context: Arsenic is a ubiquitous element present in urban air as a pollutant, and it may interfere with thyroid hormones. Objective: To evaluate the association between the personal exposure to arsenic and levels of TSH, fT4, fT3, and Tg in urban and rural workers. Materials and methods: Total urinary arsenic and thyroid markers were obtained from 108 non-smoking traffic policemen and 77 subjects working as roadmen in a rural area. Fifty subjects were monitored to evaluate airborne exposure to arsenic. Results: The mean value of exposure to arsenic was 2.9 μg/m(3) in traffic policemen, while the mean value was less than 0.1 μg/m(3) in roadmen. The mean values of urinary arsenic (10.4 μg/g creatinine vs. 5.2 μg/g creatinine; p = 0.000), TSH (1.6 μlU/ml vs. 1.3 μlU/ml; p = 0.006), fT3 (3.5 pg/ml vs. 3.7 pg/ml; p = 0.000), fT4 (1.2?ng/dl vs. 1.3?ng/dl; p = 0.000) and Tg (42.8?ng/ml vs. 36.1?ng/ml; p = 0.04) were significantly different between traffic policemen and roadmen. In traffic policemen, urinary arsenic and arsenic in the air were correlated to the airborne arsenic and TSH values, respectively. Urinary arsenic was correlated to TSH, Tg, fT3, and fT4 values. The multiple linear regression models showed the following associations: i) among urinary arsenic, arsenic in the air and job title; ii) among TSH, fT3, Tg and urinary arsenic; and iii) between fT4 and both urinary arsenic and alcohol intake. Conclusion: These results provide information about the relationship between exposure to arsenic and thyroid markers and may be useful for other categories of outdoor workers who are similarly exposed.     

Effect of lead exposure on serum immunoglobulins and reactive nitrogen and oxygen intermediate

Metal toxicants may affect immune regulation with an increased incidence of infectious diseases, cancer or autoimmune diseases. Lead is the leading environmental toxin among heavy metals and has aroused concern, as continuous low-level exposure leads to a variety of health problems. We compared serum immunoglobulins (Ig) and reactive oxygen and nitrogen intermediates (super oxide and nitric oxide (NO)) in culture supernatant of lead-exposed (blood lead; Pb-B > 10 microg/dL) individuals with that of unexposed healthy controls (blood lead < 10 microg/dL). The serum IgA level was significantly increased in lead-exposed individuals in comparison to controls (182 +/- 53 versus 138 +/- 52 mg/dL; P < 0.05). Furthermore, lipopolysaccharide-induced NO production by mouse macrophage cells, RAW 264.7, showed significant suppression (P < 0.05) after treatment with lead acetate (100 ppm). This study suggested that lead could modulate the immune system by targeting the humoral as well as innate immune cells.     

Chronic adriamycin treatment impairs myocardial interstitial neuronal release of norepinephrine and epinephrine

Although chronic adriamycin (doxorubicin) treatment is known to induce cardiomyopathic heart failure with sympathetic neurohumoral activation in a dose-dependent manner, its effect on local neuronal catecholamine release at the cardiac sympathetic nerve terminals remains to be clearly determined. Using a cardiac microdialysis technique, we measured dialysate norepinephrine (NE) and epinephrine (Epi) concentrations as indices of myocardial interstitial NE and Epi levels. respectively, in rabbits with chronic adriamycin treatment (ADR) (4 mg/kg/week, 6 weeks, n = 8) and in control rabbits (CNT) (n = 6). Exocytotic release was evoked by the local administration of KCl (100 mM) through the dialysis probe. Basal levels of NE and Epi did not differ between the ADR and CNT groups (NE, 11.6 +/- 6.6 vs. 20.4 +/- 17.2 pg/ml; Epi, 4.0 +/- 0.1 vs. 4.6 +/- 1.7 pg/ml: mean +/- SD). The exocytotic release was suppressed in the ADR compared with the CNT group (NE, 191.4 +/- 144.7 vs. 760.5 +/- 337.8 pg/ml; p < 0.05: Epi, 4.2 +/- 0.4 vs. 20.8 +/- 9.9 pg/ml; p < 0.05). We conclude that chronic adriamycin treatment impairs the neuronal exocytotic release of catecholamine at the cardiac sympathetic nerve terminals.     

Serum tumor necrosis factor-alpha in pre eclampsia

Cytokines are major contributors in pathogenesis of pre eclampsia. Serum TNF-alpha was determined in 10 normal and 30 pre-eclamptic pregnant females with special reference to maternal age, parity and levels of mean arterial blood pressure. TNF-alpha was determined using sandwich ELISA technique. Serum TNF-alpha level in normal pregnant females was 9.3 +/- 0.56 pg/ml, while in pre-eclamptic pregnant females it was 67.66 +/- 61.83 pg/ml. This increase TNF-alpha was highly significant (P < 0.001). There was no significant changes in serum TNF-alpha with respect to maternal age, parity and mean arterial pressure in both normal and pre-eclamptic pregnancies.