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K Dam

Publications and source records attributed to K Dam.

12 recordsLinked to original sources
PubMed2000

Chlorpyrifos exposure during a critical neonatal period elicits gender-selective deficits in the development of coordination skills and locomotor activity.

The widespread use of chlorpyrifos has raised concern about the potential consequences of fetal and childhood exposure. Previous studies have shown that apparently subtoxic doses of chlorpyrifos are nevertheless capable of affecting brain development by inhibiting mitosis, eliciting apoptosis, and altering neuronal activity and reactivity. To determine whether these biochemical changes elicit behavioral abnormalities, we evaluated coordination skills and open field behaviors in developing rats. Administration of 1 mg/kg s.c. of chlorpyrifos on postnatal (PN) days 1-4 elicited deficits in reflex righting on PN3-4 and in geotaxic responses on PN5-8, an effect that was specific to females. However, the ontogeny of more complex behaviors indicated a subsequent selectivity toward males. In the periweaning period, open-field locomotor activity and rearing were markedly reduced in male rats that had been exposed to chlorpyrifos on PN1-4, whereas no effect was detected in females. The gender-selective behavioral effects were associated with greater sensitivity of males to inhibition of cholinesterase in the first few hours after chlorpyrifos treatment. In contrast to the effects seen after administration on PN1-4, shifting the period of chlorpyrifos exposure to PN11-14 had a much less notable effect, even when higher doses were used: no decreases in locomotor activity and overall increases in rearing and grooming that were not significantly gender-selective. Administration on PN11-14 did not produce differential effects on cholinesterase in males and females. These studies indicate that chlorpyrifos given during a critical neonatal period, even at levels below the threshold for overt toxicity, can elicit both immediate and delayed gender-selective behavioral abnormalities. The ultimate evaluation of the developmental neurotoxicity of chlorpyrifos will thus require long-term assessments of neurobehavioral consequences of exposure during discrete developmental periods.

Animals↗
PubMed1999

Chlorpyrifos releases norepinephrine from adult and neonatal rat brain synaptosomes.

Exposure of developing animals to apparently subtoxic doses of chlorpyrifos (CPF) during a critical period of synaptogenesis has been shown to affect catecholaminergic synaptic development and neuronal activity separably from its inhibition of cholinesterase. We used rat brain synaptosome preparations to examine whether CPF has a direct effect on the release of norepinephrine (NE). Synaptosomes were preloaded with [3H]NE in the absence of CPF and were then exposed to the compound during subsequent neurotransmitter release. There was a robust increase in release at 50 microg/ml of CPF. The effect was not mediated through cholinergic receptors, as neither atropine nor mecamylamine interfered with the actions of CPF. Enhanced NE release was seen in synaptosomes derived from neonatal rat brain as well as adult rat brain, albeit with a smaller effect in neonates. Our results suggest that CPF interacts directly with presynaptic nerve terminals to influence neurotransmitter release; in the context of the immature brain, these effects can alter synaptic development through the trophic actions of catecholamines.

Aging↗
PubMed1999

Neonatal chlorpyrifos exposure alters synaptic development and neuronal activity in cholinergic and catecholaminergic pathways.

After routine home application of chlorpyrifos (CPF), infant and child exposures can exceed acceptable levels. We treated neonatal rats daily on postnatal days (PN) 1-4 (1 mg/kg) or days 11-14 (5 mg/kg), treatments that evoked no overt signs of toxicity. Effects on the development of cholinergic neuronal function were assessed using choline acetyltransferase (ChAT) activity and hemicholinium-3 (HC-3) binding as indices of synaptic proliferation and synaptic activity, respectively. In the forebrain, early CPF treatment caused a decrease in ChAT without affecting HC-3 binding; late treatment decreased HC-3 binding without affecting ChAT. In the brainstem, early treatment had no effect on either parameter but late treatment decreased both ChAT and HC-3 binding. Effects of CPF were not limited to development of cholinergic synapses but also involved catecholamine pathways. For norepinephrine or dopamine, either early or late CPF treatment evoked an increase in synaptic activity (transmitter turnover). The cerebellum, a region with sparse cholinergic innervation, was affected the most. Effects on catecholamine systems were unrelated to the magnitude or temporal pattern of cholinesterase inhibition. Our results suggest that CPF exposure during the postnatal period of synaptogenesis elicits widespread disruption of cholinergic and catecholaminergic pathways. As this is the period in which patterns of synaptic responsiveness is programmed by neural input, the period of developmental vulnerability to CPF is likely to extend into childhood.

Animals↗
PubMed1998

Uncoupling of S phase and mitosis in cardiomyocytes and hepatocytes lacking the winged-helix transcription factor Trident.

In order to maintain a stable karyotype, the eukaryotic cell cycle is coordinated such that only one round of S phase precedes each mitosis, and mitosis is not initiated until DNA replication is completed. Several checkpoints and regulatory proteins have been defined in lower eukaryotes that govern this coordination, but little is known about the proteins that are involved in mammalian cells. Previously, we have shown that the winged-helix transcription factor Trident - also known as HFH-11, FKL16 and WIN [1] [2] [3] - is exclusively expressed in cycling cells and is phosphorylated during mitosis [1] [4]. The cellular function of Trident has yet to be described, however. Here, we have shown that disruption of the Trident gene in mice resulted in postnatal death, most probably because of circulatory failure. Histological analysis of Trident -/- embryos from embryonic day 10 (E10) onwards revealed a specific, characteristic defect in the developing myocardium. The orientation of the myocytes was highly irregular and the nuclei of these disorganized cardiomyocytes were clearly polyploid with up to a 50-fold increase in DNA content. Polyploidy was also observed in embryonic hepatocytes. Our results indicate that expression of Trident is required to prevent multiple rounds of S phase in the heart and the liver. Trident therefore appears to have a role in preventing DNA re-replication during the G2 and M phases.

Animals↗
PubMed1998

Developmental neurotoxicity of chlorpyrifos: delayed targeting of DNA synthesis after repeated administration.

Despite the fact that they recover more rapidly from cholinesterase inhibition than do adults, developing animals are more sensitive to delayed neurotoxicity caused by chlorpyrifos exposure. Previous studies indicate that acute, high dose chlorpyrifos exposure of developing rats interferes with synthesis of brain macromolecules, dependent upon a critical maturational stage and upon regional disparities in cholinergic innervation. In order to determine whether chronic, lower level chlorpyrifos exposure targets similar developmental events, rats were treated daily on postnatal days 1-4, using a dose (1 mg/kg, s.c.) that caused no mortality or weight deficits and that produces minimal cholinesterase inhibition. At the end of the treatment period, we examined macromolecule synthesis in three brain regions possessing disparate maturational profiles and cholinergic innervation: the brainstem, which undergoes its primary phase of neurogenesis prenatally and develops prominent cholinergic innervation, the forebrain, which develops somewhat later but also becomes cholinergically enriched, and the cerebellum, which undergoes neurogenesis postnatally and remains poor in cholinergic innervation. Four h after the last chlorpyrifos treatment, no effects were seen for DNA, RNA or protein synthesis. However, on postnatal day 5 (24 h after the last treatment), robust deficits in DNA synthesis were observed in brainstem and forebrain, with lesser effects on the cerebellum. Although the brain regional selectivity is compatible either with differences in critical maturational phases or with targeting of cholinergically-enriched brain regions, we found no significant effects in the heart, despite the fact that it is also receives cholinergic innervation. Effects on DNA synthesis were not evident 4 h after the last dose, but then appeared after 24 h. As the 4-h point is 28 h after the third dose, this suggests that a cumulative threshold needs to be exceeded in order for the delayed neurotoxicity to appear. At the point at which DNA synthesis was inhibited in brainstem and forebrain, no effects were seen for RNA or protein synthesis, indicating selectivity for macromolecule synthesis associated with cell replication. These data indicate that otherwise subtoxic, chronic exposures to chlorpyrifos nevertheless target DNA synthesis, and by inference, cell replication, in selective brain cell populations, early events that are likely contributors to the deficits in cell number that appear several days later.

Animals↗
PubMed1998

The incidence of hyperthyroidism in Austria from 1987 to 1995 before and after an increase in salt iodization in 1990.

Between 1963 and 1990, Austria had iodized salt prophylaxis of endemic goitre with 10 mg KI (7.5 mg I) per kg. This was obviously insufficient, as urinary iodine excretion ranged from 42 to 78 microg I per g of creatinine and goitre in adults remained in the endemic range of 15%-30%. Therefore salt iodization was doubled in 1990. The aim of this study was to assess the annual incidence of different types of hyperthyroidism (HT) before and after this increase in salt iodization. The incidence of HT was recorded in 14 nuclear medicine centres from 1987 to 1995. In five additional centres data were available from 1992 onwards. Data prior to 1992 were documented retrospectively, while those after 1992 were recorded prospectively. The 14 centres drew patients from an area with a population of approximately 4.23 million while all 19 institutes were estimated to cover an area with a population of 5.4 million (the total population of Austria is 7.86 million). A total of 414232 persons were examined for the first time in the participating centres. HT and the type of HT were defined by clinical examination, serum TSH, thyroid hormone levels in blood, ultrasonography, scintigraphy and serum autoantibody titres. HT was classified into immunogenic HT (Graves' or Basedow's disease, GD) and HT with intrinsic thyroid autonomy (uni-, multinodular or disseminated Plummers' disease, PD). HT was also divided into overt (o) or subclinical (sc) disease. The following data were calculated: annual incidence per 100000 and the relative risk (RR) for HT with 95% confidence intervals (CI). In addition, linear trends were calculated for each type of HT by means of logistic regressions. In the 19 centres a total of 47834 patients with HT were registered from 1987 to 1995. PD accounted for 75% of all cases of HT and GD for 19%, while other types of HT were present in 6%. From 1987 to 1989 (time period T0), the annual incidence of oPD was 30.5 (95% CI 29.6-31.5) per 100000. The RR compared to the baseline period T0 was highest in 1992 (1.37; 1.3-1.45) and decreased to 1.17 (1.1-1.24) in 1995. The annual incidence of scPD in T0 was 27.4 (26.5-28.3) per 100000. The RR was highest in 1991 (1.64; 1.56-1.73) and was 1.60 (1. 51-1.69) in 1995. In oPD and scPD a higher RR was observed in persons older than 50 years of age, particularly in men. The incidence of oGD in T0 was 10.4 (9.8-10.9) per 100000; the maximum RR increased to 2.19 (2.01-2.38) in 1993 and decreased to 1.95 (1.78-2.13) in 1995. The incidence of scGD was 1.9 (1.6-2.1) in T0. The maximum RR was observed in 1994 (2.47; 2.04-3.0) and it was still 2.26 (1.85-2.77) in 1995. The increased incidence of oGD and scGD was evenly distributed in all ages and both sexes. The time course of different types of HT following the increase in salt iodization could be divided into two phases: an increase in the incidences of HT with peaks after 1-4 years and a subsequent decrease, the only exception being scGD. The effect was more pronounced in GD than in PD. PD showed an age and gender dependency over time, while GD did not.

Adult↗
PubMed1994

Soluble endothelium-associated adhesion molecules in patients with Graves' disease.

The targeting and recruitment of inflammatory cells to vascular endothelium in Graves' disease (GD) is mediated by intercellular adhesion molecule-1 (ICAM-1), endothelial leucocyte adhesion molecule-1 (ELAM-1), and vascular cell adhesion molecule-1 (VCAM-1). We have studied serum levels of soluble ICAM-1 (sICAM-1), soluble ELAM-1 (sELAM-1), and soluble VCAM-1 (sVCAM-1) in patients with GD (n = 21) and in patients with iodine-deficient goitre (IDG) (n = 23). The serum levels of sICAM-1 were markedly elevated in patients with GD before treatment with thiamazole (median 560 ng/ml versus 185 ng/ml in patients with IDG). In addition, elevated serum concentrations of sELAM-1 (median 85 ng/ml versus 33 ng/ml, respectively) and sVCAM-1 (median 42 ng/ml versus 15 ng/ml, respectively) were observed in patients with GD (P < 0.01 for all). The serum levels of sELAM-1 and sVCAM-1 dropped significantly after initiation of therapy and were within the normal range after 4, and 8 weeks of therapy, respectively. Serum levels of sICAM-1 were elevated even after 8 weeks of therapy. Serum levels of sVACM-1 and sICAM-1 correlated with the serum concentrations of anti-thyroid-stimulating hormone (TSH)-receptor antibodies (TSHR-R) (n = 21; r = 0.929 and r = 0.810, respectively) and anti-thyroid peroxidase antibodies (TPO-Ab) (n = 21; r = 0.673 and r = 0.750, respectively). However, no correlation between sELAM-1 and TPO-Ab, TSHR-R, and anti-thyroglobulin antibodies (Tg-Ab), respectively, could be found. In addition to thyroid hormones and autoantibodies, serum concentrations of sELAM-1 and sVCAM-1, but not sICAM-1, could be useful as clinical markers for disease activity.

Autoantibodies↗
PubMed1990

First report on the occurrence of human cases of alveolar echinococcosis in the northeast of Austria.

Since Posselt (1928) it is known, that Echinococcus multilocularis, the causative organism of alveolar echinococcosis, is prevalent in the western and southern provinces of Austria (Vorarlberg, The Tyrol, Salzburg, Carinthia, Styria). Recent distributional data confirmed the existence of these endemic areas in the mountain range of the Alps. Within the period from 1983 to 1988 human cases of obviously autochthonous alveolar echinococcosis were detected in the northeast of Austria, north of the river Danube, for the first time. This paper presents a clinical, diagnostic, therapeutical and epidemiological documentation of these three cases (2 females, 1 male), which represent the eastern most records of autochthonous E. multilocularis infections of the Central European distribution area of alveolar echinococcosis.

Austria↗
PubMed1988

[Measurements of radiocesium incorporation in 250 deceased patients who died within a year following Chernobyl].

Two months after the nuclear accident of Chernobyl, postmortem measurement of radiocaesium (137 Cs and 134 Cs) were started in different organs to study incorporation, organ distribution, and kinetics. 250 corpses were examined between July 1986 to August 1987 in the Department of pathology, St. Pölten. Highest concentrations were found in skeletal muscles, with a median value of 2.3 pCi/g wet weight (80-90% of the total incorporated dose), followed by liver, lung, spleen, kidneys, thyroid gland, heart, blood and brain, with values between 0.8 and 1.3 pCi/g. No caesium was detectable in fatty tissue. During the observation period an increase in caesium concentration was observed in almost all organs. The concentration almost doubled within 10 months in skeletal muscles. Only the lung demonstrated a decrease in the radiocaesium concentration within the first months, which can be explained only by inhalation of radiocaesium. A statistically significantly higher caesium concentration in most organs was found in females as compared with males. A possible explanation is the known lower urinary caesium concentration in women. Statistically significant correlations were found between caesium concentration and nutritional status, presence of malignancy, and the most recent intravital serum creatinine value.

Accidents↗
PubMedDate not supplied

CD15 (LeuM1) immunoreactivity: prognostic factor for sporadic and hereditary medullary thyroid cancer? Study Group on Multiple Endocrine Neoplasia of Austria.

Patients treated for sporadic and hereditary medullary thyroid carcinoma (MTC) have varying rates of persistent disease, recurrence, and survival. The aim of this study was to correlate the immunoreactivity of the monoclonal antibody CD15 (LeuM1) to initial clinical findings and the outcome of treatment. The primary tumors of 75 patients with sporadic MTC, 7 with hereditary disease, and 3 members of MEN 2A families were studied. Of these subjects 74 (87%) showed no or little immunoreactivity (< 15% positive cells; score 0) in most tumors. The remaining 13% had surgery for tumors with more than 15% cells with positive staining (score I). There was no correlation between LeuM1 immunoreactivity and sex, age, and type of MTC. There was, however, a significant correlation with the pTNM classification and UICC staging. The prognosis for patients with score 0 was significantly better than score 1 patients. CD15 immunoreactivity appears to be a predictive factor in sporadic and hereditary MTC. Lymph node dissection seems to be more successful in patients with score 0 tumors than in those with score 1 tumors. The question of reoperation in patients with recurrence of disease (especially with biochemical recurrence or persistence) should be discussed on the basis of CD15 immunoreactivity.

Adolescent↗