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Biomedical subjects

L Friedman

Publications and source records attributed to L Friedman.

370 records · Page 21Linked to original sources
PubMedDate not supplied

Comparative toxicity of polychlorinated biphenyl and polybrominated biphenyl in the rat liver: light and electron microscopic alterations after subacute dietary exposure.

The comparative toxicity of polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) in livers was studied in male Holtzman rats. Four-week-old animals were fed at dietary levels of 0, 5, 50, or 500 ppm for 5 weeks and then sacrificed. The mean liver-body weight ratios of the 50 and 500 ppm groups were increased. Histopathologic examination of the livers revealed fatty degenerative change associated with both compounds. This change was more marked at 500 than at 50 ppm. Various sized lamellar cytoplasmic inclusions were detected in livers of animals fed 500 ppm of either compound. However, the inclusions were more numerous in the PBB-treated rats. Several animals fed 50 ppm PBB had a few inclusions. In rats that received 500 ppm PBB, hypertrophic degenerative hepatocytes were present around the central veins. On the periphery of this change there were occasionally multinucleated hepatocytes. Electron microscopic examination at a dose level of 5 ppm in both the PCB and PBB groups showed a slight proliferation of smooth endoplasmic reticulum (SER), a moderate increase of lipid droplets and some liposomes, and a marked proliferation of Golgi condensing vesicles containing lipoprotein particles. A decreased number of mitochondria and lysosomes was also observed. At 50 ppm, similar but more marked ultrastructural alterations were seen. In addition, an increased number of branched and cup-shaped profiles of mitochondria and a decreased number of Golgi condensing vesicles containing lipoprotein particles were observed. Concentric membranous cytoplasmic whorls were encountered only in the 50 ppm PBB-treated rats. At 500 ppm the number of mitochondria decreased in both groups. There was also a marked increase in the number of SER and liposomes concomitant with a decreased number of Golgi condensing vesicles containing lipoprotein granules. Membranous whorls were also present in the 500 ppm groups.

Animals↗
PubMedDate not supplied

Comparative toxicity of polychlorinated biphenyl and polybrominated biphenylin the rat thyroid gland: light and electron microscopic alterations after subacute dietary exposure.

The comparative toxicity of polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) in thyroid glands was studied in male Holtzman rats. Four-week-old animals were fed at dietary levels of 0, 5, 50, and 500 ppm for 5 weeks and then sacrificed. PCB and PBB produced similar dose-dependent ultrastructural lesions in thyroid follicular cells of rats. The daily administration of 5 ppm of either PCB or PBB resulted in the accumulation of large membrane-limited colloid droplets and electron-dense lysosomal bodies within the cytoplasm of follicular cells. Microvilli were short and abnormally branched, and unique cytoplasmic processes extended from the apical surface of follicular cells into the luminal colloid. Similar but more severe ultrastructural changes were observed in thyroid glands of rats administered 50 and 500 ppm of either PCB or PBB. Many follicular cells were distended with large abnormal lysosomal bodies and colloid droplets. Mitochondria were often vacuolated with disrupted cristae. Microvilli were blunt with abnormal branching or absent from areas of the luminal surface of follicular cells. Processes of apical cytoplasm often extended into the follicular lumen in areas devoid of microvilli. Follicular cells remained responsive after the feeding of either PCB or PBB and underwent moderate compensatory hypertrophy and hyperplasia. Thyroid follicles were smaller than in controls and were lined by more columnar cells that occasionally formed papillary projections into the follicular lumens. PCB and PBB produced similar ultrastructural lesions in thyroid follicular cells which appeared to interfere with the synthesis and secretion of thyroxine.

Animals↗
PubMedDate not supplied

Testicular atrophy and impaired spermatogenesis in rats fed high levels of the methylxanthines caffeine, theobromine, or theophylline.

Experiments were designed to determine the effects of feeding the methylxanthines caffeine, theobromine, or theophylline to 4- to 6-week-old males rats at a dietary level of 0.5 percent for periods ranging from 14 to 75 weeks. In the first two experiments, Osborne-Mendel rats were fed the test substances alone or in combination with sodium nitrite to test the hypothesis that these amines might nitrosate in vivo to produce toxic nitrosamine compounds. The compounds failed to produce neoplastic or preneoplastic lesions, but a significant positive finding was the occurrence of severe bilateral testicular atrophy with aspermatogenesis or oligospermatogenesis in 85-100 percent of the rats fed caffeine or theobromine. In a third experiment the methylxanthines were fed to Holtzman rats for 19 weeks to determine whether testicular atrophy would be induced in a second strain of rat. The testicular effects were similar to those in Experiments I and II but were more pronounced. Caffeine and theobromine induced testicular injury in nearly all rats. Theophylline induced severe testicular atrophy in 14 percent of the rats, mild to moderate atrophy in 71 percent, and had no effect in 15 percent. The relative testicular toxicity of the methylxanthines was caffeine, most potent; theobromine, slightly less potent; and theophylline, considerably less potent. Somewhat variable atrophic changes of the accessory sexual organs (epididymis, prostate, and seminal vesicles) accompanied the testicular changes. Cytogenetic analysis of testes from caffeine- or theophylline-treated rats revealed a significantly reduced number of mitotic cells in the caffeine-treated group. Plasma testosterone concentrations were significantly elevated in the theobromine group and somewhat elevated in the caffeine-treated group; this correlated morphologically with an apparent hyperplasia of interstitial cells in severely atrophied testes in these groups. Plasma cholesterol concentrations were significantly increased in the caffeine and theobromine groups. Possible sites and mechanisms of action of the methylxanthines in the induction of testicular atrophy and impaired spermatogenesis are discussed.

Animals↗
PubMedDate not supplied

Testicular atrophy and impaired spermatogenesis in rats fed high levels of the methylxanthines caffeine, theobromine, or theophylline.

Experiments were designed to determine the effects of feeding the methylxanthines caffeine, theobromine, or theophylline to 4- to 6-week-old male rats at a dietary level of 0.5 percent for periods ranging from 14 to 75 weeks. In the first two experiments, Osborne-Mendel rats were fed the test substances alone or in combination with sodium nitrite to test the hypothesis that these amines might nitrosate in vivo to produce toxic nitrosamine compounds. The compounds failed to produce neoplastic or preneoplastic lesions, but a significant positive finding was the occurrence of severe bilateral testicular atrophy with aspermatogenesis or oligospermatogenesis in 85-100 percent of the rats fed caffeine or theobromine. In a third experiment the methylxanthines were fed to Holtzman rats for 19 weeks to determine whether testicular atrophy would be induced in a second strain of rat. The testicular effects were similar to those in Experiments I and II but were more pronounced. Caffeine and theobromine induced testicular injury in nearly all rats. Theophylline induced severe testicular atrophy in 14 percent of the rats, mild to moderate atrophy in 71 percent, and had no effect in 15 percent. The relative testicular toxicity of the methylxanthines was caffeine, most potent; theobromine, slightly less potent; and theophylline, considerably less potent. Somewhat variable atrophic changes of the accessory sexual organs (epididymis, prostate, and seminal vesicles) accompanied the testicular changes. Cytogenetic analysis of testes from caffeine- or theophylline-treated rats revealed a significantly reduced number of mitotic cells in the caffeine-treated group. Plasma testosterone concentrations were significantly elevated in the theobromine group and somewhat elevated in the caffeine-treated group; this correlated morphologically with an apparent hyperplasia of interstitial cells in severely atrophied testes in these groups. Plasma cholesterol concentrations were significantly increased in the caffeine and theobromine groups. Possible sites and mechanisms of actions of the methylxanthines in the induction of testicular atrophy and impaired spermatogenesis are discussed.

Animals↗
PubMedDate not supplied

INDANA: a meta-analysis on individual patient data in hypertension. Protocol and preliminary results.

The overall effect of antihypertensive drug treatment has been well documented. The proportion of patients who benefit varies according to their baseline cardiovascular risk, and is small for the majority of people treated. Some investigators propose limiting the treatment target population to patients at high cardiovascular risk, but several assumptions must be made to justify this procedure. The INDANA project is a meta-analysis based on individual patient data, and thus offers the opportunity to check the validity of these assumptions. Its main objective is to identify responders (and non-responders) in the drug treatment of hypertension. The rationale and methods for such an approach are presented here, with the solution for some technical problems. The conclusion of the data collection has shown that the project is feasible. The results of the main analysis should be available in 1996, and should contribute to the selection of responders and to the individualization of the treatment of hypertension.

Humans↗