Certified reference materials for radionuclides in Bikini Atoll sediment (IAEA-410) and Pacific Ocean sediment (IAEA-412).

The preparation and characterization of certified reference materials (CRMs) for radionuclide content in sediments collected offshore of Bikini Atoll (IAEA-410) and in the open northwest Pacific Ocean (IAEA-412) are described and the results of the certification process are presented. The certified radionuclides include: (40)K, (210)Pb ((210)Po), (226)Ra, (228)Ra, (228)Th, (232)Th, (234)U, (238)U, (239)Pu, (239+240)Pu and (241)Am for IAEA-410 and (40)K, (137)Cs, (210)Pb ((210)Po), (226)Ra, (228)Ra, (228)Th, (232)Th, (235)U, (238)U, (239)Pu, (240)Pu and (239+240)Pu for IAEA-412. The CRMs can be used for quality assurance and quality control purposes in the analysis of radionuclides in sediments, for development and validation of analytical methods and for staff training.

Study of solvent-protein coupling effects by neutron scattering.

The present work aims to characterize the dynamical behavior of proteins immersed in bio-preserving liquids and glasses. For this purpose, the protein dUTPase was chosen, while the selected solvents were glycerol, a triol, and some homologous disaccharides, i.e., trehalose, maltose, and sucrose, which are known to be very effective bio-preserving agents. The results highlight that the disaccharides show a slowing down effect on the water dynamics, which is stronger for trehalose than in the case of the other disaccharides. Furthermore, a characterization of the medium which hosts the protein is performed by using an operative definition of fragility based on the mean square displacement extracted by elastic incoherent neutron scattering, which is directly connected to Angell's kinetic fragility based on the viscosity. Finally, a study of the dynamics of the protein sequestered within the solvents is performed. The result shows that the protein dynamics is coupled with that of the surrounding matrix.

Correlated species differences in the effects of cannabinoid ligands on anxiety and on GABAergic and glutamatergic synaptic transmission.

Cannabinoid ligands show therapeutic potential in a variety of disorders including anxiety. However, the anxiety-related effects of cannabinoids remain controversial as agonists show opposite effects in mice and rats. Here we compared the effects of the cannabinoid agonist WIN-55,212 and the CB1 antagonist AM-251 in CD1 mice and Wistar rats. Special attention was paid to antagonist-agonist interactions, which had not yet been studied in rats. In mice, WIN-55,212 decreased whereas AM-251 increased anxiety. The antagonist abolished the effects of the agonist. In contrast, WIN-55,212 increased anxiety in rats. Surprisingly, the antagonist potentiated this effect. Cannabinoids affect both GABAergic and glutamatergic functions, which play opposite roles in anxiety. We hypothesized that discrepant findings resulted from species differences in the relative responsiveness of the two transmitter systems to cannabinoids. We investigated this hypothesis by studying the effects of WIN-55,212 on evoked hippocampal inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs). IPSCs were one order of magnitude more sensitive to WIN-55,212 in mice than in rats. In mice, IPSCs were more sensitive than EPSCs to WIN-55,212. This is the first study showing that the relative cannabinoid sensitivity of GABA and glutamate neurotransmission is species-dependent. Based on behavioural and electrophysiological findings, we hypothesize that WIN-55,212 reduced anxiety in mice by affecting GABA neurotransmission whereas it increased anxiety in rats via glutamatergic mechanisms. In rats, AM-251 potentiated this anxiogenic effect by inhibiting the anxiolytic GABAergic mechanism. We suggest that the anxiety-related effects of cannabinoids depend on the relative cannabinoid responsiveness of GABAergic and glutamatergic neurotransmission.

Radionuclide monitoring strategy for food-chain in Hungary.

Annually about 3000 samples including foodstuff, feeding material, environmental samples, among them bioindicators are examined by the Radiological Monitoring Network of the Ministry of Agriculture and Regional Development. Environmental monitoring strategy and major properties of the network are described. The median value of specific activity of (137)Cs in all kinds of foodstuff produced in Hungary is below 0.1B q/kg fresh weight, based on regular countrywide survey. The committed effective dose due to ingestion for adults was estimated to be 0.6 microSv for (90)Sr and 0.3 microSv for (137)Cs in 2004 according to a conservative estimation. It is shown how (137)Cs contamination due to the accidental release from the steel mill in Algeciras, Spain in 1998 could be detected by a county station of the network making use of the database of the whole network.

Cannabinoid CB1 receptor dependent effects of the NMDA antagonist phencyclidine in the social withdrawal model of schizophrenia.

Clinical and laboratory findings suggest that cannabinoid signalling is implicated in schizophrenia. However, the interaction remains poorly understood, as data are often contradictory. Here we investigated wild-type (WT) and cannabinoid CB1 receptor-knockout (CB1-KO) mice in the phencyclidine-induced social withdrawal model of schizophrenia. N-methyl-D-aspartate (NMDA) antagonists (including phencyclidine) induce psychotic symptoms in humans, and are used to model schizophrenia in a variety of experimental conditions. In WTs, 5 mg/kg phencyclidine increased locomotion and stereotyped behaviours, and decreased social interactions. These changes are consistent with a schizophrenia-like effect. In CB1-KOs, phencyclidine decreased locomotion, enhanced ataxia and stereotypy more markedly than in WTs, but did not affect social interactions. Locomotion showed a significant negative correlation with both ataxia and stereotypy, suggesting that in CB1-KOs, the locomotor suppressive effect of phencyclidine was secondary to changes in these variables. Our findings demonstrate that CB1 gene disruption dramatically alters the behavioural effects of the NMDA antagonist phencyclidine, suggesting that the CB1 receptor is involved in schizophrenia. As social disruption and stereotypy respectively are believed to model negative and positive symptoms of schizophrenia, our findings tentatively suggest that cannabinoids are differentially involved in these two symptom categories. These findings require verification by experiments involving CB1 receptor blockers, as the genetic and pharmacological blockade of receptors may not always provide similar results.

CB1 cannabinoid receptors mediate anxiolytic effects: convergent genetic and pharmacological evidence with CB1-specific agents.

Cannabinoids are known to modulate GABAergic and glutamatergic transmission in cortical areas, the former via CB1 and the latter via a novel receptor. Pharmacological data demonstrate that several widely used cannabinoid ligands bind to both receptors, which may explain the inconsistencies in their behavioural effects. Earlier we showed that the cannabinoid antagonist SR-141716A affected behaviour in both CB1 knockout and wild-type animals, and its effect (anxiolysis) was different from that of CB1 gene disruption (anxiogenesis). In the present experiments, we studied the effects of the CB1 antagonist AM-251, and the cannabinoid agonist WIN-55,212-2 in wild-type as well as in CB1 knockout mice. CB1 knockout mice showed higher scores of anxiety-like behaviour than the wild-type animals in the elevated plus-maze. Selective blockade of CB1 receptors by AM-251 (0.3, 1 and 3 mg/kg) increased anxiety-like behaviour dose-dependently in the wild-type mice but had no effect in the knockouts. In wild types, the cannabinoid agonist WIN-55,212-2 (1 and 3 mg/kg) caused a decrease in anxiety-like behaviour, which was abolished by the CB1-selective antagonist AM-251 (3 mg/kg). The same agonist did not change plus-maze behaviour in CB1 knockout animals. These data demonstrate at the behavioural level that AM-251 and, at low concentrations, WIN-55,212-2, are selective ligands of the CB1 cannabinoid receptor in mice. Our studies on the behavioural effects of the cannabinoid antagonist SR-141716A and the CB1 antagonist AM-251 show that the CB1 and the novel cannabinoid receptor mediate anxiolytic and anxiogenic effects, respectively. This suggests that agonists of the former, or antagonists of the latter, are promising new compounds in the pharmacotherapy of anxiety.

Context-dependent effects of CB1 cannabinoid gene disruption on anxiety-like and social behaviour in mice.

Contrasting data were reported regarding the effects of cannabinoids on anxiety and social behaviour in both animals and humans. The cognitive effects of cannabinoids and their interactions with the HPA-axis raise the possibility that cannabinoid effects are context but not behaviour specific. To assess this hypothesis, we submitted CB1 receptor knock-out (CB1-KO) and wild-type (WT) mice to tests, which involved similar behaviours, but the behavioural context was different. The elevated plus-maze test was performed under less and more anxiogenic conditions, i.e. under low and high light, respectively. We also compared the social behaviour of the two genotypes in the resident/intruder and social interaction tests. Both tests represent a social challenge and induce similar behaviours, but involve different contexts. The behaviour of CB1-KO and WT mice was similar under low light, but CB1 gene disruption increased anxiety-like behaviour under the high light condition. CB1 gene disruption promoted aggressive behaviour in the home-cage, whereas it inhibited social behaviour in the unfamiliar cage. Thus, the anxiogenic-like effect was restricted to the more stressful unfamiliar environment. These data suggest that the effects of CB1 gene disruption were context and not behaviour specific. Novelty stress resulted in higher ACTH levels in CB1-KOs than in WTs, which suggests that context dependency occurred in conjunction with an altered HPA axis function. The present data at least partly explain contrasting effects of cannabinoids in different contexts as well as in different species and strains that show differential stress responses and coping strategies.

[The influence of depression on the effect of Tropisetron in the therapy of fibromyalgia]. / Beeinflusst die Depressivität den Behandlungseffekt von Tropisetron bei Fibromyalgiepatienten?

As described elsewhere the oral administration of 5 mg of the 5-HT3-receptor-antagonist Tropisetron in fibromyalgia exhibited less amelioration of pain in patients with a depression in comparison to patients without depression. Since an intravenous treatment seems to increase the effect of Tropisetron, the question arises whether patients with depression profit from the intravenous therapy. Methods 68 out patients with fibromyalgia according to ACR-criteria were enrolled in the study. The patients filled in a VAS pain and the Beck Depression Inventory (BDI) before and after a bolus i.v. injection of 5 mg Tropisetron for 5 days [Beck AT, Steer Ra. Beck-Depression-Inventory (BDI) In: Hautzinger M (Hrsg der dt. Ausg.). Testhandbuch. 1. Auflage Bern: Verlag Hans Huber, 1994]. In the beginning the patients had to have > or = 40 mm in the VAS pain from 0-100 mm. The patients were divided into three groups: group 1 = patients with a BDI<19 without experience with antidepressive drugs (n=26); group 2=patients with a BDI > or = 19 (n=22) and negative experience with antidepressive substances, and group 3=patients with a BDI > or = 19 and an accompanying antidepressant drug therapy and some benefit under this therapy (n=20). Results Before the therapy there was no significant difference in VAS pain in the groups, but in BDI there was a significant difference between group 1 (BDI mean value 11.5) in comparison to group 2 (BDI mean value 26.1) and group 3 (BDI mean value 24.8). After therapy all three groups had a significant amelioration of pain: group 1: p=0.000023; group 2: p=0.00073; group 3: p=0.0145. There was a significant difference between the group with BDI<19 and the group with antidepressant drug in amelioration of pain (p=0.044). A significant correlation was found in group 2 with Beck > or = 19 between amelioration of pain and BDI after therapy (p=0.008, r=0.666). In this group a pain-reactive depression and in group 3 an endogenous depression must be discussed.

IgE-mediated anaphylaxis to Thiomucase, a mucopolyssacharidase: allergens and cross-reactivity.

BACKGROUND: Thiomucase is a mucopolysaccharidase obtained from ovine tissues mainly used to facilitate the diffusion of local anaesthetics and in the treatment of cellulitis. A patient with an anaphylaxis in relation to the intramuscular administration of Thiomucase is reported. OBJECTIVE: To investigate Thiomucase allergens and their possible relationship with dander allergens and animal albumins. MATERIAL AND METHODS: Skin prick tests (SPT) and serum-specific IgE were performed with Thiomucase and danders. Thiomucase SDS-PAGE immunoblotting was performed in order to study allergens. RAST/CAP inhibition and SDS-PAGE immunoblotting inhibition were carried out to study the cross-reactivity. RESULTS: Skin prick tests (SPT) were positive to Thiomucase, animal dander (cat, dog, sheep, other), bovine serum albumin (BSA), and echinococcus. Specific IgE was also positive to Thiomucase, animal dander (cat, dog, sheep, other), BSA and echinococcus. In the RAST-CAP inhibition assays BSA was nearly completely inhibited by Thiomucase, Thiomucase was partially inhibited by BSA and cat and Echinococcus granulosus was partially inhibited by sheep and Thiomucase. In the Thiomucase SDS-PAGE immunoblotting several proteins fixed IgE, ranging from 20 kDa to > 94 kDa, the strongest with 43 kDa. The IgE fixation to BSA, cat and sheep in the SDS-PAGE immunoblotting was completely inhibited by the preincubation of the serum with Thiomucase. CONCLUSIONS: An IgE-mediated anaphylaxis to Thiomucase is documented. Multiple allergens are recognized in Thiomucase by the patient serum, the main with 43 kDa. Partial cross-reactivity with BSA, cat dander and sheep dander is documented.

The seasonal changes in the concentration of polycyclic aromatic hydrocarbons in precipitation and aerosol near Lake Balaton, Hungary.

The concentration of polycyclic aromatic hydrocarbons (PAHs) in atmospheric precipitation and aerosol samples was monitored in a rural site by Lake Balaton, Hungary to examine the seasonal variation. The seasonal mean concentration of individual 3-6-ring PAHs in precipitation varied from 1 to 54 ng l-1 and from 3 to 350 ng l-1 in summer and winter, respectively. In the atmospheric aerosol samples the seasonal mean concentration of PAHs varied from 4 to 880 pg m-3, from 4 to 300 pg m-3, from 11 to 1050 pg m-3 and from 36 to 5000 pg m-3 in spring, summer, autumn and winter, respectively. Wet (412 micrograms m-2 year-1) and aerosol (190-300 micrograms m2 year-1) deposition rates were also estimated indicating that the two processes are of comparable importance in the removal of 3-6-ring PAHs from the atmosphere.

Fibromyalgia treatment with intravenous tropisetron administration.

A prospective, randomized, placebo-controlled, multicenter, double-blind trial in fibromyalgia patients demonstrated that peroral daily treatment with 5 mg tropisetron for 10 days produced a significant reduction in pain and other symptoms. The aim of the present study was to determine whether intravenous administration of 2 mg tropisetron daily for a limited period of time would produce quicker and more favorable results. In the first cohort 18 fibromyalgia patients received a single intravenous injection of 2 mg tropisetron. In the second cohort 24 fibromyalgia patients were treated with 2 mg intravenous tropisetron daily for 5 days. Pain intensity was measured with the visual analog scale and the pain score. Pain at tender and control points (dolorimeter) as well as 17 ancillary symptoms before and after treatment were evaluated. Pain intensity was followed-up by means of a patient diary until recurrence. Dolorimetry revealed that a single intravenous injection of 2 mg tropisetron significantly reduced pain and enhanced pain threshold. These effects, however, lasted for only a few days. Of 18 patients in the first cohort, only three showed no response to therapy. Of the 24 patients in the second cohort, 23 showed pain reduction when 2 mg tropisetron was administered daily for 5 days. Pain relief lasted for 2 weeks to 2 months in 20 of these patients. Two patients stopped filling in the pain diary. Twelve ancillary symptoms such as sleep disturbances, fatigue, morning stiffness were also significantly improved by the latter treatment. In the global assessment 16 out of 24 patients showed significant improvement and seven showed slight improvement. Only one patient experienced no improvement. Tolerability was good. In conclusion, intravenous injection of 2 mg of the 5-hydroxytryptamine3 receptor antagonist tropisetron once daily for 5 days produced a longer-lasting therapeutic effect on fibromyalgia symptoms than did peroral daily treatment with 5 mg of this drug. The results achieved are currently being evaluated in a randomized, placebo-controlled, double-blind trial.

Isolation of water-soluble organic matter from atmospheric aerosol.

The development of a solid phase extraction (SPE) method is presented, which is capable of isolating approx. 60% of the water-soluble organic compounds from aerosol samples. The aqueous extracts of the filter samples were acidified then passed through an SPE column. Four silica-based and two polymeric reversed phase columns were tested and similar recoveries of the organic carbon were found. The isolated organic matter was nearly free from inorganic ions, which are major constituents of atmospheric aerosol. This fraction accounted for a major part of the UV absorption above 250 nm and fluorescence activity of the aerosol extract. The precision of the method was tested by performing three parallel sample preparations with Oasis HLB columns. It was found that the relative standard deviation of the carbon content of the isolated organic matter was better than 7%, which indicated the reliability of the method. In the atmospheric aerosol research the newly developed sample preparation method facilitates the physical and chemical characterisation of water-soluble organic compounds without the interference of inorganic constituents.

Oral treatment of fibromyalgia with tropisetron given over 28 days: influence on functional and vegetative symptoms, psychometric parameters and pain.

The 5-HT3 receptor antagonists are a novel therapy for patients suffering from fibromyalgia, although the optimal duration of treatment is still unclear. The objective of this phase II study was to evaluate whether prolonging treatment with tropisetron to 4 weeks is tolerable and correlated with an improved clinical benefit. Thirty female patients with fibromyalgia received oral tropisetron (5 mg) daily for 28 days in an open-label fashion. Treatment resulted in significantly decreased pain as measured by visual analog scale (VAS), with a mean reduction of 59.7% and an absolute median change of -25.0 from baseline to day 28 (p<0.0001). A similar, significant reduction of 55.7% and absolute median change of -31.0 was observed in the painscore (p<0.0001). The response rate with patients showing a > or = 35% reduction in individual pain scores was 72.4% at day 28. The pressure tolerance of tender-points was slightly increased at the end of the treatment period. In addition, significant improvements were observed in the State-Trait-Anxiety-Inventory (STAI), scales of von Zerssen (Bf-S) and Beck Depression Index (BDI). Functional symptoms were compared with the results from a 10-day, randomized, double-blind phase III study of tropisetron in 418 fibromyalgia patients. In both studies several functional symptoms such as sleep disturbances and dizziness improved significantly (p<0.05). In the 28 days study, the number and extent of improvement in functional symptoms was increased compared with the shorter trial. Tolerability and safety of tropisetron was good, and typically for 5-HT3-receptor antagonists, gastrointestinal symptoms and headache were the most frequently reported events. In conclusion, 28 days treatment of fibromyalgia patients with 5 mg tropisetron resulted in significant pain reduction, which was most pronounced after 10 days with a further reduction up to day 28. Psychometric tests showed significant improvements in depression and anxiety state scores, while functional symptoms improved with extended tropisetron treatment.

Sample preparation of atmospheric aerosol for the determination of carbonyl compounds.

Sample preparation including sonication and solid phase extraction has been developed for the determination of carbonyl compounds in atmospheric aerosol. Aerosol samples were sonicated in acidified acetonitrile containing 2,4-dinitrophenylhydrazine (DNPH) to form hydrazone derivatives of aldehydes and ketones. Water was added to the extract to increase its polarity. Then the solution was passed through an octadecyl or phenyl solid phase extraction cartridge. The concentrated hydrazone derivatives were eluted with tetrahydrofuran, the eluate was evaporated to dryness then dissolved in acetonitrile/water mixture and finally analysed by RP-HPLC with UV detection at 360 nm. The absolute detection limits of the individual carbonyl compounds range from 0.4 to 5.8 ng.

Zinc protection against cadmium-induced infertility in female rats. Effect of zinc and cadmium on the progesterone production of cultured granulosa cells.

Adult female rats were treated subcutaneously (s.c.) with zinc chloride (ZnCl2, 10 or 20 mg kg-1 body weight, bw) four times during two ovarian cycles. The third injection was accompanied by cadmium chloride (CdCl2) administration sc (2.5, 5 and 10 mg kg-1 bw). The fourth zinc (Zn) treatment was followed by mating. ZnCl2 (20 mg kg-1) itself impaired fertility by 20%, while CdCl2 dose-dependently blocked the receptivity of female rats. In combination with 2.5 and 5 mg kg-1 CdCl2 the metal salts decreased fertility in an additive fashion, whereas at the highest CdCl2 dose (10 mg kg-1) a marked ameliorating effect of ZnCl2 (10 and 20 mg kg-1) on cadmium (Cd)-caused sterility was observed. In the pregnant animals apart from the higher Cd-induced blood progesterone levels and reduced body weight gain of dams, no significant treatment-related maternal and fetal effects could be observed. ZnCl2 (10 to 80 microM) and CdCl2 (10 to 80 microM) were added to the culture medium of ovarian granulosa cells. CdCl2 suppressed follicle-stimulating-hormone- (FSH-) and cAMP-stimulated progesterone accumulation. No protective effect of Zn against Cd-induced drop in progesterone production could be seen, while Zn by itself induced a significant increase in FSH-supported progesterone synthesis. In conclusion, while Zn protected against Cd-induced sterility in vivo, it failed to counteract the direct effect of Cd on steroid biosynthesis. The data indicate that Zn protection does not take place at the level of ovary. Moreover, Zn and Cd seem to affect FSH-stimulated progesterone production by different mechanisms.

Effect of cadmium on female fertility, pregnancy and postnatal development in the rat.

Adult female rats having regular ovarian cycles were treated with 2.5, 5 or 10 mg/kg cadmium chloride (CdCl2) during estrus or diestrus and mated 32, 80 or 132 h post-treatment. Sperm positivity was checked next day on the predicted estrus. Maternal effects during pregnancy, fetal outcome on day 10 or at term as well as postnatal development of the F1 generation were recorded. CdCl2 caused sterility in 40 or 87% of animals at doses 5 and 10 mg/kg, respectively. Influence of Cd on fertility depended on the day of the cycle, and on the time elapsed between treatment and mating. The Cd-caused overt toxicity in fertile female rats was expressed by dose-dependent decrease in maternal body weight gain and increased progesterone blood levels. No treatment-related alteration in number and weight of conception day 10 of pregnancy or in weight and size of litters, rate of males and females at term and during the 21-day post-parturition study could be seen. It is concluded that Cd given prior mating may lead to sterility in a dose-dependent fashion. This is suggested to be caused by anovulation resulting from reversible pituitary disfunction. Animals proving fertile in spite of Cd-treatment have developed tolerance against Cd in terms of fetal outcome and postnatal development.

Age dependent accumulation of cadmium in the human ovary.

Cadmium (Cd) was determined by atomic absorption spectrophotometry in small pieces (< 1 g) of healthy human ovaries excised for histologic examination. Cd levels in the ovary increased linearly between 30 and 65 years of age. Below 30 years, there was no age dependent increase and over 65 a tendency was observed for ovarian Cd levels to decrease. There was no difference in the Cd content of fresh luteal and nonluteal tissue taken from regularly cycling ovaries. In smokers, the amount of Cd in the ovaries was elevated compared to nonsmokers. In multiparous women (more than 3 children) a tendency of decreased Cd ovarian levels was observed. There was no difference between ovarian Cd content of physical and mental workers. It can be proposed that Cd may be a risk factor for conception and pregnancy in women in their forties.

Altered ovarian progesterone secretion induced by cadmium fails to interfere with embryo transport in the oviduct of the rat.

The effect of Cadmium (Cd) on embryo transport through the oviduct and on ovarian progesterone (P) secretion were studied in the rat. Animals were given 2.5, 5, 10 mg/kg CdCl2 or 1.0 mL/kg NaCl sc on day 1 of pregnancy. On days 1, 2, 3, 4, and 5, they were anesthetized with pentobarbital, cannulae were inserted in one of the utero-ovarian veins, and 5-minute blood samples were taken from the ovary. Ovarian venous outflow was recorded, P was determined from the blood fractions, and secretion rates were calculated. P levels were determined in peripheral blood. Body weights and the wet weight of adrenals, ovaries, and oviducts were checked; oviducts and uterine horns were flushed; and number, location, and developmental stage of embryos were observed. Cd content of the oviducts was measured. Cd accumulated dose and time dependently in oviducts and induced a dose-dependent depression and delay in the rise of ovarian P secretion during days 1 through 5 of pregnancy. In the peripheral blood, P levels also failed to rise until day 4 of pregnancy in Cd-treated rats. In embryo transfer, however, no alteration could be observed. It is hypothesized that lack of vascular contact in the oviduct makes it possible for the preimplantation embryos to escape toxic effects of Cd.

Cadmium interferes with steroid biosynthesis in rat granulosa and luteal cells in vitro.

Recently, cadmium has been described to disturb ovarian function in rats. In this paper the direct influence of cadmium on steroid production of ovarian cells in vitro has been studied. Granulosa and luteal cells were obtained from proestrous and pregnant rats, and incubated with 0, 5, 10, 20 or 40 micrograms ml-1 CdCl2 in the presence or absence of 0.1-1000 ng ml-1 follicle stimulating hormone (FSH) or luteinizing hormone (LH) for 24 or 48 h. Production of progesterone (P) and 17 beta-estradiol (E2) by granulosa and that of P by luteal cells were measured by radioimmunoassay. In FSH-stimulated granulosa cell cultures, 5 and 40 micrograms ml-1 CdCl2 suppressed P accumulation to 65 and 10%, respectively; accumulation of E2 (at 5 micrograms ml-1 CdCl2) decreased to 44%. P production of LH-supported luteal cells dropped to 86 and 66%, respectively, when 5 and 40 micrograms ml-1 CdCl2 was added to the medium. No alteration in basal P accumulation occurred in granulosa and luteal cell cultures following incubations with 20 and 40 micrograms ml-1 CdCl2, whereas basal E2 production of granulosa cells was markedly diminished. It is concluded that CdCl2 suppressing steroid synthesis in vitro exerts a direct influence on granulosa and luteal cell function.

Distribution of cadmium in ovaries, adrenals and pituitary gland after chronic administration in rats.

Wistar rats were given 0.25, 0.5 or 1.0 mg/kg/week CdCl2 for 14, 18 or 22 weeks and the body weight, Cd content of ovaries, adrenals, pituitary gland, furthermore the progesterone and oestradiol-17 beta secretion of ovary were checked. Cd treatment caused a slight decrease in the body weight, but failed to alter the weight of endocrine organs. CdCl2 in a dose of 0.25 mg/kg/week resulted in almost the same Cd content in all the three organs. Rising the amount of Cd administered the pituitary gland accumulated more Cd than the adrenals, and the lowest levels were found in the ovary. CdCl2 even in the dose of 1.0 mg/kg/week failed to alter the ovarian cycle, progesterone and oestradiol-17 beta production of ovary. The data point also to a developing tolerance to Cd as the cumulative dose of CdCl2 lies close to the LD50 levels.