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Biomedical subjects

A Abramovici

Publications and source records attributed to A Abramovici.

At least 55 records · Page 3Linked to original sources

Early stages of the pathogenesis of rat ventral prostate hyperplasia induced by citral.

Typical lesions of benign prostatic hyperplasia (BPH) were induced experimentally in the ventral prostate of adolescent (6 week old) male rats by citral, a nonsteroidal compound. Incipient BPH changes were already observed in the acinar glands 10 days after citral administration. A longer period of treatment (1 month) significantly enhanced epithelial hyperplasia, whereas the stromal elements were less reactive. Characteristic BPH lesions involving both prostatic compartments were found after 3 months of treatment. Castration prior to citral administration prevented such BPH changes; however, citral did not prevent the involutive lesions of castration. The mechanism of action of citral is yet unknown, various possibilities concerning the induction of BPH in rats are presented and discussed. The potential advantage of this model, especially as BPH is not necessarily linked to age or exogenous hormones, may offer new alternative pathways for understanding the complexity of BPH pathogenesis in animals and perhaps even in man.

Acyclic Monoterpenes↗

Neurological mutation characterized by dysmyelination in NCTR-Balb/C mouse with lysosomal lipid storage disease.

Morphological and biochemical studies were performed on the CNS of neurologically affected NCTR-Balb/C mouse. Histological and electron microscopic techniques demonstrated severe myelin deficiency in the affected brains. Neither the presence of lipid-containing macrophages nor reactive gliosis was apparent. Analysis of myelin-associated lipids and proteins revealed prominent depletion of galactocerebroside, sulfatide, and proteolipid proteins. In contrast to the scarcity of myelin-specific constituents a marked accumulation of GM2 and GM3 gangliosides and several neutral glycolipids, i.e., glucocerebroside, lactosylceramide, gangliotriaosylceramide, and gangliotetraosylceramide were found in affected CNS. These abnormalities were already apparent in 12-day-old pups as well as in 65-day-old mice. A significant deficit in the proportion of long-chain fatty acids (C24), notable in both normal and alpha-hydroxy acids of cerebrosides from affected white matter, was measured. The lack of reactive gliosis, the observed depletion of galactocerebroside and sulfatide at the early age of 12 days, and the relative decrease in long-chain fatty acids in affected CNS strongly suggest a defect in myelinogenesis in this mutant rather than a secondary process of myelin breakdown.

Animals↗

Assessment of splenic function in dogs following arterial ligation and autotransplantation.

Two methods for the preservation of splenic function following trauma to the spleen were studied and compared in dogs and puppies. One method was splenectomy and autotransplantation of small pieces of splenic tissue, and the other--ligation of the main branches of the splenic artery after partial splenectomy. Dogs subjected to splenectomy alone or laparotomy alone served as controls. Splenic function was assessed on the basis of resistance to sepsis by virulent pneumococci. Cultures were obtained from the blood, peritoneal fluid and intraabdominal organs 3 days after i.v. injection of the pneumococci; none of the adult dogs in any of the groups had positive cultures. Among splenectomized puppies, 55.5% had positive cultures for pneumococci, whereas those which underwent ligation of the splenic artery and partial splenectomy had negative cultures. Microscopic examination of the autotransplants revealed loss of the characteristic structure of splenic tissue, whereas in the dogs in which the splenic artery had been ligated, the spleen showed numerous islands of tissue with well-preserved follicular structure. We suggest that in children with severe splenic trauma, ligation of the splenic artery may provide a promising alternative to splenectomy.

Animals↗

The hemolytic activity of citral: evidence for free radical participation.

In the present investigation the hemolytic properties of citral were examined. Tests with different concentrations of citral showed that hemolysis of rat erythrocytes commenced after a lag period the length of which depended on the concentration of the hemolysin and tended to 100% hemolysis. Comparison of the characteristics of the hemolysis induced by high and low citral concentrations, indicated that two mechanisms are involved--a non specific steroid--terpenoid or glutathione depletion mechanism dominating at high citral concentrations and a free radical mechanism dominating at low citral concentrations. Experiments performed with various free radical scavengers indicate that 1O2 might be involved.

Acyclic Monoterpenes↗

Molecular structure-teratogenicity relationships of some fragrance additives.

The embryotoxic effect of some flavour additives was tested on young chick embryos. A certain correlation between the molecular structure of a compound and its teratogenic expression was observed. The presence of an unsaturated bond at C2 near a carbonyl function was found to be more effective than its saturated analogs or the alcoholic derivatives. Short chains or semicyclic structures, as well as additional -OH groups might favour the embryotoxic impact. An additional finding was that the teratogenic effect of a compound seems to be modulated by the dose related lethal effect. A uniform phenotypic expression of the malformation was the rule for all the tested compounds. The possible interreaction between the liposoluble unsaturated carbonyl compounds and the lipid constituents of the embryonic cell membrane is offered as a mechanism for the teratogenic activity of some flavour additives.

Abnormalities, Drug-Induced↗

Sebaceous glands changes following topical application of citral.

The long-lasting effect of a flavour cosmetic constituent on male rat skin was studied. Topical daily application of citral (15.4%) solution for 3 months produced an increase in the number of sebaceous gland lobules and hyperplasia of sebaceous cells in each gland. It is suggested that the mechanism of this hyperplasia might be activation of the testosterone 5 alpha-reductase which induces the formation of dihydrotestosterone, the mediator of sebaceous gland activity.

Acyclic Monoterpenes↗

Arterial wall renin.

Aortic homogenates contain proteolytic enzymes which will release angiotensin I (AI) from renin substrate. Some of these are active at low pH and are probably unrelated to renin. Renin-like activity in the rat measured at the optimum pH of 6.5 is altered in parallel with plasma renin in a wide variety of situations. The two diverge only in non-steady state situations. Studies have therefore been carried out after bilateral nephrectomy and after the injection of renal renin into nephrectomized rats. In each case aortic renin-like activity was cleared much more slowly than plasma renin, and the blood pressure change was related to aortic renin-like activity rather than to plasma renin. The blood pressure response to the converting enzyme inhibitor teprotide was also related to the former rather than the latter. Immunofluorescent studies of the aorta and the intrasplenic arteries from rats injected with mouse renin showed that renin was taken up predominantly into the media and persisted at this site. Thus, the uptake of renal renin from plasma by both large and small arteries is probably an important step in the physiology of the renin-angiotensin system and mediates renin-induced changes in peripheral resistance and blood pressure. However, we have no evidence for the hypothesis that selective accumulation of renin in the resistance vessel walls causes hypertension when circulating levels of renin are normal.

Animals↗

Histopathological features of the skin in hypopituitarism and Laron-type dwarfism.

Skin biopsies from children and adolescents with various syndromes of somatomedin deficiency revealed changes in structure and in distribution of the dermal elastin fibers as compared with a group of seven healthy control subjects. In 18 patients with isolated growth hormone deficiency (IGHD) and in 11 with multiple pituitary hormone deficiencies (MPHD), the number of elastin fibers was reduced; the individual fibers were shorter and slimmer than usual, and frequently arranged in groups dispersed in various directions. Skin biopsies from six patients with Laron-type dwarfism (LTD) revealed mostly thickened elastin fibers, frequently arranged in irregular bundles, but the number of elastin fibers was normal in prepubertal patients and reduced only in postpubertal patients. The reduction of elastin fibers in these patients was less prominent than in IGHD. The finding of more numerous elastin fibers in LTD than in IGHD is suggestive of a direct nonsomatomedin-mediated effect of human growth hormone on skin elastogenesis.

Adolescent↗

Chemical and biochemical studies in fetuses affected with Nieman-Pick disease type A.

Chemical and biochemical studies were performed on two unrelated fetuses affected with Niemann-Pick disease type A, following abortion at about the 19th week of gestation. Abortion was performed as a consequence of previous findings, in amniotic fluid cell cultures, that sphingomyelinase activity was completely absent. Phospholipid analyses of various organs of the fetuses, spleen and liver were the organs mostly affected. Interestingly enough considerable accumulation of sphingomyelin was found in the placenta. The brain was the only organ in which sphingomyelin storage could not be proved. In addition to sphingomyelin a slight accumulation of cholesterol was noticed. Deficiency of sphingomyelinase activity measured at pH 5.0 was the general characteristic of the affected tissues. It is concluded that the accumulation of sphingomyelin in various organs throughout the body of fetuses affected with Niemann-Pick disease is suggestive of the essential role of the enzyme sphingomyelinase and its biochemical maturation, even during the early stages of gestation.

Amniotic Fluid↗

Changes in glycosaminoglycan composition of normal human placentas with maturation.

Crude glycosaminoglycan preparations were isolated from acetone-powder of first-, second-, and third-trimester human placentas. Glycosaminoglycan composition was examined by electrophoresis and densitometric scanning before and after treatment with testicular hyaluronidase and chondroitinase ABC. Hexosamines were determined in electrophoretic fractions in order to identify the individual glycosaminoglycans. The results showed a decrease in glycosaminoglycans and an increase in protein contents in the preparations as the placenta matured. The main glycosaminoglycans in all placentas were dermatan sulfate, chondroitin sulfates, hyaluronic acid, and heparan sulfate. With aging of the placenta, the proportion of hyaluronic acid remained unchanged and that of chondroitin sulfate decreased, whereas the proportions of dermatan and heparan sulfates increased. Age-dependent changes in the glycosaminoglycan composition of the placenta appear to follow a pattern similar to that reported for other mammalian tissues.

Chondroitin Sulfates↗

Glycosaminoglycan patterns in diabetic and toxemic term placentas.

Crude glycosaminoglycans were prepared from acetone powder of diabetic, toxemic, and normal term placentas. Glycosaminoglycan composition was determined by electrophoresis and densitometric scanning with and without treatment with testicular hyaluronidase and chondroitinase ABC. The identity of individual glycosaminoglycans was confirmed by the nature of their hexosamine. Glycosaminoglycan content was found to be significantly increased in diabetic placentas and increased to a lesser degree in the toxemic placentas. The amount of hyaluronic acid was elevated in both abnormal tissues, and heparan sulfate was slightly higher in diabetes, while unchanged in toxemia. Dermatan sulfate was markedly reduced in the abnormal placentas while chondroitin 4/6 sulfate was unaltered. An attempt was made to correlate the histopathologic changes reported to occur in these conditions with the alterations in the glycosaminoglycans patterns of placentas.

Chondroitin Sulfates↗

Experimental limb dysmorphogenesis as a model of chemical injury response in undifferentiated embryonic tissues: a light and electron microscopical study.

A histopathological and ultrastructural analysis of the early stage of limb dysmorphogenesis from 1 hr to 48 hr, following citral administration is presented as a model for studying the reaction to injury of undifferentiated embryonic tissues. Early lesions such as cloudy swelling, hydropic degeneration, enlargement of the extracellular space and retraction of protoplasmic extensions were observed 1 hr after treatment, affecting both epiderm and mesenchyme of the limb. Few pyknotic cells were encountered during the early stages. Cell necrosis and autophagocytosis became more conspicuous at 12 hr post-injection. About the same time the first signs of healing were observed, charcterised by heterophagocytosis and return of mitotic activity. The epiderm being more differentiated, regenerates ad integrum and more rapidly than the mesenchyme. The evolution of these pathological events, which proceed in a spatio-temporal cascade, seem to reflect the pharmacokinetic gradient of the cell-teratogen interactions. The type of limb malformation will depend mainly on the extent of injury and/or healing of the mesenchymal mass, rather than on the injury and/or healing of the surface ectoderm. It is concluded that the reaction to chemical injury of undifferentiated tissues partially mimics the destructive and repair process in adult tissues, but differs in lacking some basic constituents such as oedema, monocyte exudation and granulation tissue formation.

Abnormalities, Drug-Induced↗

Chemical and biochemical studies in human fetuses affected with Niemann-Pick disease type A.

Chemical and biochemical studies were performed on two unrelated fetuses affected with Niemann-Pick disease type A, following abortion at about the 19th week of gestation. Abortion was performed as a consequence of previous findings, in amniotic fluid cell cultures, that sphingomyelinase activity was completely absent. Phospholipid analyses of various organs of the fetuses revealed an excess of sphingomyelin in all viscera as compared to control nonaffected fetuses. Spleen and liver were the organs mostly affected. Interestingly enough considerable accumulation of sphingomyelin was found in the placenta. The brain was the only organ in which sphingomyelin storage could not be proved. In addition to sphingomyelin a slight accumulation of cholesterol was noticed. Deficiency of sphingomyelinase activity measured at pH 5.0 was the general characteristics of the affected tissues. It could be concluded that the accumulation of sphingomyelin in various organs throughout the body of fetuses affected with Niemann-Pick disease, was suggestive of the essential role of the enzyme sphingomyelinase and its biochemical maturation, even during the early stages of gestation.

Brain↗

Selective oocyte degeneration and impaired fertility in rats treated with the aliphatic monoterpene, Citral.

Mature female rats treated with Citral (3-7-dimethyl-2,6-octadienal) either topically for 60 or 100 days or by 6 i.p. injections (at 4-5 day day intervals) showed a marked decrease in the number of normal follicles per section, because oocytes tended to degenerate although the follicular cells remained normal. The reproductive performance after Citral treatment was impaired: there was a reduction in implantation number and litter size and an increased post-implantation fetal wastage. None of the young survived after 100 days of topical Citral treatment. It is suggested that Citral directly affects the oocytes.

Acyclic Monoterpenes↗

Myeloschisis in a six weeks embryo of a leukemic woman treated by busulfan.

A case of myeloschisis in a six weeks old human embryo is reported. The 39-year-old mother was treated by busulfan before and during the early stages of gestation for chronic lymphatic leukemia. Additional histological findings consisted in a decrease of mesenchymal elements together with a somitic disorganisation in the affected area of the embryo. In spite of the well known experience that this drug is well tolerated by leukemic pregnant women, a possible interference of busulfan with the oocyte differentiation in this elderly primipara is proposed.

Abnormalities, Drug-Induced↗