Embryonic death in mouse due to lead exposure.

Female mice which displayed a vaginal plug after mating were given a diet containing 0, 0.125, 0.250, 0.500% of lead as lead acetate and were dissected 16 to 18 days later. Lead treatment was found to reduce significantly the incidence of pregnancies and to increase the postimplantation loss in the pregnant females.     

Developmental exposure to organic lead causes permanent hippocampal damage in Fischer-344 rats

Summary The long-term consequences of neonatal exposure to triethyl lead, the putative neurotoxic metabolite of the anti-knock gasoline additive tetraethyl lead, were examined with respect to central nervous system (CNS) development. We presently report a series of studies in which exposure of neonatal rats to organic lead produces profound CNS damage in adulthood as indicated by dose-dependent, persistent behavioral hyperreactivity as well as dose-dependent, preferential, and permanent damage to the hippocampus. General morphological parameters of brain development were not altered. Pharmacological probes of neurotransmitter system integrity suggested a functional and dose-dependent relationship between this behavioral hyperreactivity and hippocampal damage via cholinergic, but not dopaminergic, pathways. Furthermore, these alterations were not accompanied by long-term alterations in motor activity and were not attributable to the presence of lead in adult neural tissue. Finally, these behavioral, anatomical, and pharmacological indices of developmental exposure to organic lead were dissociable from any effects of early undernutrition. These data collectively indicate that organolead compounds may pose a potent neurotoxic threat to the developing CNS.     

Developmental exposure to organic lead causes permanent hippocampal damage in Fischer-344 rats

The long-term consequences of neonatal exposure to triethyl lead, the putative neurotoxic metabolite of the anti-knock gasoline additive tetraethyl lead, were examined with respect to central nervous system (CNS) development. We presently report a series of studies in which exposure of neonatal rats to organic lead produces profound CNS damage in adulthood as indicated by dose-dependent, persistent behavioral hyperreactivity as well as dose-dependent, preferential, and permanent damage to the hippocampus. General morphological parameters of brain development were not altered. Pharmacological probes of neurotransmitter system integrity suggested a functional and dose-dependent relationship between this behavioral hyperreactivity and hippocampal damage via cholinergic, but not dopaminergic, pathways. Furthermore, these alterations were not accompanied by long-term alterations in motor activity and were not attributable to the presence of lead in adult neural tissue. Finally, these behavioral, anatomical, and pharmacological indices of developmental exposure to organic lead were dissociable from any effects of early undernutrition. These data collectively indicate that organolead compounds may pose a potent neurotoxic threat to the developing CNS.     

Lipid accumulation in mouse hepatocytes after morphine exposure

Summary After morphine injection lipid accumulation in mouse hepatocytes begins within 2 h and continues for 24 h when most hepatocytes are filled with lipid droplets. In spite of morphine maintenance the liver recovers as the accumulated lipids are coupled with protein and subsequently transported and released into the perisinusoidal space of Disse.Supported by USPHS Grants GM 15490, 5 SO7 RR05386-16 and DA-01310.     

Pre- and postnatal lead exposure affects the serotonergic system in the immature rat brain

Summary The effect of pre- and postnatal lead exposure on the development of the serotonergic system in striatum and brain stem was investigated. Serotonin and its metabolite 5-HIAA where determined by HPLC-EC. A significant decrease of 5-HT was detected in the brain stem at postnatal day 28. At both days 6 and 28 postnatal, 5-HIAA was reduced in striatum and brain stem. The results provide support to the hypothesis that developing 5-HT neurons are sensitive to relatively low levels of lead exposure.     

Pre- and postnatal lead exposure affects the serotonergic system in the immature rat brain.

The effect of pre- and postnatal lead exposure on the development of the serotonergic system in striatum and brain stem was investigated. Serotonin and its metabolite 5-HIAA where determined by HPLC-EC. A significant decrease of 5-HT was detected in the brain stem at postnatal day 28. At both days 6 and 28 postnatal, 5-HIAA was reduced in striatum and brain stem. The results provide support to the hypothesis that developing 5-HT neurons are sensitive to relatively low levels of lead exposure.     

Functional state of mouse liver mitochondria in toxicoses due toAspergillus flavus andPenicillium rubrum

Zusammenfassung Es wurde die funktioneile Integrität der Mitochondrien nach Verunreinigung der Nahrung mitA. flavus undP. rubrum aus vergifteter Mäuseleber untersucht. Die Mitochondrienfunktion der mitP. rubrum vergifteten Leber ist in bezug auf ihre ATPase-Tätigkeit und oxydative Phosphorylierung gestört, während im mitA. flavus vergifteten Gewebe alle wichtigen Mitochondrienfunktionen unverändert blieben.     

Block to pseudopregnancy in mice caused by exposure to male urine

Zusammenfassung Mäuseweibchen, die durch Paarung mit vasektomierten Männchen scheinträchtig gemacht worden waren, wurden dem Urin von Männchen eines anderen Stammes ausgesetzt. Dadurch wurde die Pseudogravidität unterbrochen. Diese Beobachtung gleicht der Unterbrechung der Trächtigkeit frisch begatteter Weibchen durch den Urin fremdstämmiger Männchen und bestätigt auch die Beschleunigung des Eintritts des Östrus durch die Gegenwart der Männchen.     

Rad51 and DNA-PKcs are involved in the generation of specific telomere aberrations induced by the quadruplex ligand 360A that impair mitotic cell progression and lead to cell death

Functional telomeres are protected from non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways. Replication is a critical period for telomeres because of the requirement for reconstitution of functional protected telomere conformations, a process that involves DNA repair proteins. Using knockdown of DNA-PKcs and Rad51 expression in three different cell lines, we demonstrate the respective involvement of NHEJ and HR in the formation of telomere aberrations induced by the G-quadruplex ligand 360A during or after replication. HR contributed to specific chromatid-type aberrations (telomere losses and doublets) affecting the lagging strand telomeres, whereas DNA-PKcs-dependent NHEJ was responsible for sister telomere fusions as a direct consequence of G-quadruplex formation and/or stabilization induced by 360A on parental telomere G strands. NHEJ and HR activation at telomeres altered mitotic progression in treated cells. In particular, NHEJ-mediated sister telomere fusions were associated with altered metaphase-anaphase transition and anaphase bridges and resulted in cell death during mitosis or early G1. Collectively, these data elucidate specific molecular and cellular mechanisms triggered by telomere targeting by the G-quadruplex ligand 360A, leading to cancer cell death.     

Photoreceptor damage following exposure to excess riboflavin

Flavins generate oxidants during metabolism and when exposed to light. Here we report that the photoreceptor layer of retinas from black-eyed rats is reduced in size by a dietary regime containing excess riboflavin. The effect of excess riboflavin was dose-dependent and was manifested by a decrease in photoreceptor length. This decrease was due in part to a reduction in the thickness of the outer nuclear layer, a structure formed from stacked photoreceptor nuclei. These changes were accompanied by an increase in photoreceptor outer segment autofluorescence following illumination at 328 nm, a wavelength that corresponds to the excitation maxima of oxidized lipopigments of the retinal pigment epithelium.     

Human health effects of exposure to cadmium

Summary The health effects of human exposure to cadmium are discussed with emphases on intake, absorption, body burden, and excretion; osteomalacia in Japan; hypertension; and proteinuria, emphysema, osteomalacia, and cancer in workers. Elevated blood pressure has not been observed as a result of excessive exposures to cadmium in Japan or the workplace. Renal tubular dysfunction and consequent proteinuria is generally accepted as the main effect following long-term, low-level exposure to cadmium. Studies of workers show that proteinuria may develop after the first year of exposure or many years after the last exposure. Proteinuria and deterioration of renal function may continue even after cessation of exposure. The immediate health significance of low-level proteinuria is still under debate. However, there is evidence that long-term renal tubular dysfunction may lead to abnormalities of calcium metabolism and osteomalacia. The few autopsy and crosssectional studies of workers do not permit conclusions to be drawn regarding the relationship between cadmium exposure and emphysema. Retrospective and historical-prospective studies are needed to settle this important question. No conclusive evidence has been published regarding cadmium-induced cancer in humans. However, there is sufficient evidence to regard cadmium as a suspect renal and prostate carcinogen. Because of equivocal results and the absence of dose-response relationships, the studies reviewed should be used with caution in making regulatory decisions and low-dose risk assessments.     

Antarctic fishes survive exposure to carbon monoxide

The extensive in vivo conversion of haemoglobin to the carbon monoxide derivative has no discernible effect on the survival of the red-blooded Antarctic fishPagothenia bernacchii. Analysis of caudally sampled blood of cannulated specimens revealed that reconversion of carbon-monoxy haemoglobin to oxyhaemoglobin was complete within 48 hours. Thus, under stress-free conditions, haemoglobin is not necessary for survival ofP. bernacchii. Red-blooded Antarctic fishes can carry oxygen necessary for routine delivery dissolved in plasma, in a similar way to the haemoglobinless Channichthyidae, although they lack the morphological and physiological adaptations which allow the latter to prosper without any haemoglobin.     

Neuronal cell deficits following maternal exposure to methadone in rats

Summary Rat offspring were maternally subjected to methadone hydrochloride during gestation or lactation. At 21 days of age, the area of the pyramis (cerebellar lobule VIII) in prenatally and postnatally exposed groups was reduced 45% and 36%, respectively, from control levels, and the total number of internal granule neurons/section was reduced 49% and 46%, respectively; the number of granule neurons/mm² in both groups was 75% of control values. Based on histological evaluation the timetable of cerebellar morphogenesis was unaltered in rats prenatally exposed to methadone, suggesting a permanent neuronal deficit, but cerebellar development was markedly delayed in animals subjected postnatally.This work was supported by National Institute on Drug Abuse grant DA-01618.     

Response due to 0 somatic antigen ofShigella dysenteriae in rabbits

Zusammenfassung Hochgereinigtes Antigen vonShigella dysenteriae bewirkte eine signifikante Temperatursteigerung in Kaninchen.     

After-potentials due to an electrogenic pump in molluscan giant neurons

Resumen En un grupo de neuronas centrales de caracol, cada potencial de actión es seguido invariablemente por una onda hiperpolarizante. Esta onda no es debida a un aumento de permeabilidad de la membrana; aumenta en duración y voltage a medida que se aumenta el nÚmero de potenciales de action que la producen y es eliminada reversiblemente por inhibidores metabólicos. Se la interpreta como producida por una bomba electrogénica que extruye las cargas que penetraron al soma neuronal durante el potencial de acción.