The Effects of Allyl Isovalerate on the Hematopoietic and Immunologic Systems in Rodents

The Effects of Allyl Isovalerate on the Hempatopoietic and ImmunologicSystems in Rodents. HONG, H. L., HUFF, J. E., LUSTER, M. I.,MARONPOT, R. R., DIETER, M. P., HAVES, H. T., AND BOORMAN, G.A. (1988). Fundam. Appl. Toxicol. 10, 655–663. FemaleB6C3F1 mice plus male and female Fischer 344/N rats were gavagedwith allyl isovalerate (AIV) in corn oil at 0, 31,62, or 125(mice) and 0, 31. 62, 125, or 250 (rats) mg/kg body weight forfive daily exposures per week for a 2-week period. Hematologic,immunologic, and histopathologic studies were performed 48 to72 hr following the final treatment. AIV exposure had no effecton hematology or bone marrow cellularity in mice or rats. AIVexposure at 250 mg/kg was toxic to rats causing reduced weightgain and hepatotoxicity. In vivo and in vitro studies revealedthat pluripotent hematopoietic stem cells (CFU-S) and granulocyte-macrophageprogenitors (CFU-GM) in the bone marrow were decreased in thetreated mice. Hematopoietic suppression was correlated withthe reduction in the hexose monophosphate shunt metabolism ofbone marrow cells but the Embden-Meyerhof pathway and tncarboxylicacid pathway enzymes did not appear to be affected. Examinationof host resistance following Plasmodium and Listeria challengedid not demonstrate significant differences between treatedand control mice, nor were there other effects on the immunesystem. This suggests that the myelotoxic effects were minimaland of a degree that would not alter host resistance.     

The Effects of Magnetic Resonance Imaging on Implantable Pulse Generators

The effects of magnetic resonance imaging were assessed on four dual chamber and two single chamber pulse generators. The tests were performed with a resistive, water-cooled magnet operating at 0.15 T. The 6.4-MHz radiofrequency (RF) field was operated at a maximum power of 1,000 watts with a period adjusted from 130 to 500 ms. Reed switch closure occurred in all six pulse generators tested when placed near the entrance of the magnetic resonance imaging scanner, and the generators reverted to asynchronous operation unless programmed to the "magnet off" mode. None of the pulse generators exhibited any alterations in programmed parameters or in the ability to be reprogrammed after RF pulsing. When the RF field was turned on, there was no change in the asynchronous paced cycle length in four pulse generators; however, during RF scanning there was rapid cardiac stimulation at the RF pulse period in one single chamber and one dual chamber pulse generator.     

Contractile Responses and Structure of Small Bronchi Isolated from Rats after 20 Months' Exposure to Ozone

Short-term exposure to high concentrations of ozone has beenshown to increase airway responsiveness in normal humans andin all laboratory animal species studied to date. While ourknowledge concerning the pulmonary effects of single exposuresto ozone has increased rapidly over recent years, the effectsof repeated exposures are less understood. The goal of the presentstudy was to determine whether airway responsiveness is increasedafter near-lifetime exposure to ozone. Airway segments representingapproximately eighth generation airways were isolated from Fischer344 rats of both genders that had been exposed for 6 hr perday, 5 days per week for 20 months to 0, 0.12, 0.5, or 1.0 partsper million (ppm) ozone. Circtimferential tension developmentwas measured in isolated airways in response to bethanechol,acetylcholine, and electrical field stimulation. Responsivenessof the airways to the contractile stimuli was described by theeffective dose or frequency that elicited half-maximum contraction(ED50) and the maximum response. Since ozone exposure is associatedwith remodeling of peripheral airways, smooth muscle area wasdetermined and tension responses were normalized to the areameasurements. Before normalization of tension data to smoothmuscle area, neither the ED50 nor maximum response of smallbronchi to the contractile stimuli was altered after chronicozone exposure. Smooth muscle area was greater in airways isolatedfrom animals that had been exposed to 0.5 ppm ozone. After accountingfor smooth muscle area, maximum responses of the small bronchiisolated from male rats were significantly reduced after 0.12and 0.5 ppm ozone. Although not significant statistically, asimilar trend was observed in airways isolated from female rats.These results suggest that the increase in airway responsivenessassociated with acute ozone exposure does not persist duringnear-lifetime exposure. Although the mechanism responsible forthe adaptation to the effects of 03 on airway responsivenessis unknown, the results indicate that smooth muscle cell functionwas compromised by the chronic exposure. The mechanism(s) responsiblefor mediating this effect and the relevance of these resultsto humans remains to be determined.     

Infants born to narcotic dependent mothers: Physical growth patterns in the first 12 months of life

Objectives: To describe the physical growth patterns of infants born to narcotic dependent mothers (INDM) over a 12 months period and, if possible, to relate the growth to drug taking patterns during pregnancy.
Methodology: The growth of a cohort of 43 INDM was measured during the first 12 months of life. Weight and length measurements were compared with percentile charts and converted to Z scores. Questionnaire data about drug taking practices, demographic variables and the neonatal period (including withdrawal scores) were obtained.
Results: Twenty-four (55.8%) of INDM had evidence of neonatal drug withdrawal requiring treatment with phenobarbitone. At birth, Z scores for weight and length indicated relative intrauterine growth retardation. By 12 months, there had been some catch up growth, but Z scores for weight and length were still below zero. Persistent weight retardation at 12 months was correlated with methadone dosage during pregnancy, but not the need for phenobarbitone therapy.
Conclusions: The growth patterns of INDM in the first 12 months of life indicated that at birth there was evidence of intrauterine growth retardation, but by 12 months the growth was little different from the rest of the community. There appears to be some influence of narcotic agents taken while pregnant on subsequent growth of INDM.     

Eosinophilia and resistance to Schistosoma haematobium in man

We have measured the levels of infection with Schistosoma haematobium in children resident in an endemic area of The Gambia before and 3 months after successful chemotherapy and following reinfection. An exposure index was calculated from data collected on water contact, cercarial densities and infected snail densities at water contact sites. Peripheral blood eosinophil levels were recorded and the ability of serum (heat inactivated) from the children to allow killing of schistosomula of S. haematobium was examined. Of 50 children with a post-treatment egg count of less than 1 ovum/10 ml urine, 26 were classified as reinfected, acquiring greater than 1 ovum/10 ml urine over the transmission season. Twenty-four were classified as not reinfected, acquiring less than 1 ovum/10 ml of urine over the same period. These two groups did not differ with respect to their estimated age, weight or pretreatment egg counts. Children who were reinfected had significantly higher levels of exposure and significantly lower peripheral blood eosinophil counts than children who were not reinfected. At all levels of exposure children with high eosinophil counts were less likely to be reinfected than those with lower counts. But antibody-dependent, complement-independent killing of schistosomula of S. haematobium by eosinophils was barely detectable and did not differ between reinfected and non reinfected groups. These observations suggest that subjects with elevated counts are less susceptible to reinfection but the mechanisms involved are not apparent.     

Apolipoprotein E alleles in nonagenarian subjects in the Belfast Elderly Longitudinal Free-living Ageing Study (BELFAST)

The ApoE gene has three alleles coding for the proteins apoE2, apoE3 and apoE4. E4 has been reported to be associated with hypercholesteraemia, ischaemic heart disease, age-related cognitive decline and Alzheimer's disease. Conversely, the E2 allele has been associated with longevity in French centenarians and their siblings. In this study, we have assessed any shift in the ApoE genotypes in nonagenarian subjects from Belfast where there is a high intrinsic incidence of cardiovascular disease. ApoE phenotypes were determined by electrofocusing and immunoblotting in 114 Senieur-approximated subjects >90 years old and compared with 2071 subjects, 30--65 years of age, recruited from the same geographical area by the MONItoring of CArdiovascular trends study group in Belfast (MONICA). The E4 allele was reduced in the nonagenarian group (X(2)=11.1; P=0.0006), the E3 unchanged and E2 frequency was increased (X(2)=4.0; P=0.047). These results suggest that longevity is negatively associated with the E4 allele and may be associated with carriage of E2.     

Shades of gray matter: Noninvasive optical images of human brain reponses during visual stimulation

Recent theories about human brain function emphasize the need for imaging methods that allow the study of dynamic interactions among different structures. In this paper, we report on a new technique, based on the measurement of parameters of migration of near-infrared photons, that yields functional images of the human occipital cortex, combining a spatial resolution of 0.5 cm and a temporal resolution of 50 ms. This technique appears to be suitable for studying the dynamics of cortical activation.