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Biomedical subjects

A Abramovici

Publications and source records attributed to A Abramovici.

At least 19 recordsLinked to original sources

Effects of senescence and citral on neuronal vacuolar degeneration in rat pelvic ganglia.

A significant part of the morbidity in elderly men involves pelvic organs and their autonomic neural regulation. Environmental stimuli also impair the structure and function of pelvic organs. One of these factors is citral, a widely-used cosmetic fragrance constituent, which causes severe prostatic hyperplasia in rats. In this study, we assessed the effect of topical administration of citral (30 days) on the morphology of pelvic ganglia (PG) in young adult and old Wistar rats. Neuronal vacuolar degeneration with preserved nuclei of PG neurons was observed in untreated senescent, but not young rats. Citral significantly increased the rate of vacuolated neurons in old rats (from 3 to 14%), but only slightly in young ones (from 0 to 0.5-0.3%). Similar lesions were not found in inferior cervical or celiac ganglia, in either group. This shows that environmental stimuli enhance age-related processes of vacuolar neuronal degeneration in PG, and may contribute to the dysfunction of pelvic organs in the elderly.

Acyclic Monoterpenes↗

Dominant negative Met reduces tumorigenicity-metastasis and increases tubule formation in mammary cells.

Activation of the Met tyrosine kinase growth factor receptor by its ligand HGF/SF has been shown to increase in vitro invasiveness in epithelial cell lines. To study the effect of Met-HGF/SF signaling in breast cancer cells, we transfected met, hgf/sf and dominant negative (DN) forms of met into the poorly differentiated metastatic murine mammary adenocarcinoma cell line DA3. These cells express moderate levels of endogenous Met, which is rapidly phosphorylated in response to HGF/SF treatment. Met+hgf/sf transfection results in significantly increased tumorigenic and metastatic activity in vivo accompanied by reduced tubule formation. DA3 cells transfected with DN forms of Met (DN-DA3) exhibit reduced Met phosphorylation following exposure to HGF/SF. Furthermore, as compared to the parental cells, the DN-DA3 cells exhibit diminished in vitro scattering and invasiveness, while in vivo they display greatly reduced tumorigenicity and spontaneous metastasis. Tumors emanating from DN-DA3 cells injected to BALB/C mice are highly differentiated and display extensive tubule formation. These results suggest that Met-HGF/SF signaling is a determining factor in the delicate balance between differentiation/tubule formation and tumorigenicity-metastasis. Oncogene (2000) 19, 2386 - 2397

Adenocarcinoma↗

Induction of atypical prostatic hyperplasia in rats by sympathomimetic stimulation.

BACKGROUND: Prostatic innervation may participate in its homeostasis and growth. alpha-Adrenergic inhibition alleviates clinical symptoms in benign prostatic hyperplasia. However, the prostatic effect of adrenergic agonists has not been investigated. This study deals with the prostatic effect of subchronic sympathomimetic stimulation. METHODS: Male rats received daily subcutaneous injections of the alpha-adrenergic agonist phenylephrine, 1, 10, or 20 mg/kg per day, the beta-adrenergic agonist isoproterenol, 1, 2.5 or 5 mg/kg per day, or saline, for 30 days, and the prostates were removed for histopathological examination. RESULTS: Phenylephrine induced atypical prostatic hyperplasia, characterized by piling-up with papillary and cribriform patterns, and budding-out of epithelial cells. It decreased prostatic secretions and total weight. Similar results were observed in orchidectomized rats receiving exogenous testosterone supplementation. Isoproterenol had no prostatic morphological effect. CONCLUSIONS: These results raise the possibility that sympathetic stimuli play a role in normal and aberrant growth and differentiation of prostatic epithelium, and suggests neurostimulants-treated animals as a model to study the etiology and development of prostatic hyperplasia.

Adrenergic alpha-Agonists↗

Role of chronic inflammation in the promotion of prostatic hyperplasia in rats.

PURPOSE: Chronic prostatitis is a common histopathological finding in prostatectomized patients. A possible interrelationship between the presence of leukocyte exudate and the extent of the hyperplastic lesions has been suggested. The aim of the present study was to analyze the effect of the immunomodulator compounds, Complete Freund Adjuvant (CFA) and cyclosporin A (CsA), administered alone or together with citral on the induction and extent of rat prostatic hyperplasia. MATERIALS AND METHODS: Adolescent Wistar rats (42 days old) were given citral alone or combined with CFA or CsA for one month. Semiquantitative analysis of the extent of the hyperplastic lesions was made with the histoscore protocol. RESULTS: CsA did not induce hyperplastic changes or abolish the ability of citral to promote hyperplastic changes or to affect the extent of the lymphocytic exudate in the stroma. CFA itself, however, had a proliferative action on the prostatic epithelium, and it augmented the hyperplastic changes induced by citral and even induced atypical transformations of the acinar epithelium. CONCLUSIONS: Immunoinflammatory stimulators might play a role in the prostatic epithelial cell growth and proliferation processes, most probably by modulation of the cytokine system.

Acyclic Monoterpenes↗

Intraarticular minocycline injection in experimental synovitis.

Minocycline, a semi-synthetic tetracycline, was injected into one hind joint of twenty-two rabbits with zymosan-induced arthritis, while the contralateral joint served as a control. A local inflammatory reaction was observed a few days after the zymosan injection. Most clinical parameters such as knee diameter, systemic temperature, sedimentation rate and blood cell count did not change throughout the experiment both in control and minocycline treated rabbits. However, the zymosan platelet counts rose from 3.4x10(5)/microL to 5x10(5)/microL, as well as the level of serum fibrinogen (from 99 mg% to 370 mg%). Microscopically, a perivascular infiltrate consisting of lymphocytes and polymorphonuclear cells was seen. Lymphoid follicles as well as plasma cells epitheloid and giant cells were also observed. A mild tendency to fibrosis and lesser inflammatory reaction in the minocycline treated knees was noted. Our data suggest that intraarticular minocycline treatment did not alleviate the course of the rheumatoid-like inflammatory reaction of the knee joint.

Animals↗

Citral and testosterone interactions in inducing benign and atypical prostatic hyperplasia in rats.

Citral is a monoterpene in wide use as an aromatic supplement in the cosmetics and food industries. Previous studies in our laboratory have shown that cutaneous application of citral on adolescent rats may induce benign prostatic hyperplasia (BPH)-like and even atypical hyperplastic changes in the ventral lobes. In the present study we investigate the possible interactions between citral and serum testosterone levels on the induction of hyperplastic changes in the ventral prostate of adolescent rats. In addition, the study includes a comparative analysis of normal intact rats showing circadian variations of serum testosterone levels and rats in whom this rhythmic pattern was abolished either by excessive supplementation of exogenous androgen or by castration. Our results demonstrate an induction of benign as well as atypical prostatic hyperplasia following citral application. The most severe atypical changes were noted in the citral-treated rats with high serum testosterone levels. Although the mechanism of action of citral is yet unknown, the present results suggest a synergism between citral and testosterone resulting in hyperplastic changes in the rat ventral prostate. In addition, the results reconfirm that serum testosterone levels fluctuate according to a circadian rhythm in intact young and adolescent male rats. The application of citral tends to lower the morning circadian peaks, and the circadian pattern was abolished in orchiectomized rats and in those treated with testosterone implants.

Acyclic Monoterpenes↗

Immediate vasoactive effect of citral on the adolescent rat ventral prostate.

The vasoactive effect of a fragrance compound, citral, on rat ventral prostate is presented. A combined method of Indian-ink perfusion and postfixation transparency was used. One single dose of citral applied on the back skin of the rat induced an immediate triple response-like effect on the prostatic vascular bed. A slight vasodilatation appeared already after 2 1/2 min, followed by a marked vasoconstriction process after 5-min postcitral administration. Toward the period of 10 min, a second vasodilatation process was noted which persisted for the following 24 hr of observation. This study has demonstrated that changes in the microvascularization of the rat prostate can be estimated by counting the number of carbon-stained blood vessels. The results obtained by this technique are closely related with the findings in the vascular network profile of the macroangiographic observations. The mechanism of action of citral on the microvascularization of the rat ventral prostate is yet unknown. Based on the present findings, we suggest that the neoplastic capacity of citral upon the prostatic epithelia is activated via a nonspecific inflammatory reaction modulated either by local release of neurotransmitters or throughout a direct effect of citral on the endothelial cells.

Acyclic Monoterpenes↗

Translocation of bacteria due to direct mucosal damage caused by Gastrografin. An experimental study in newborn rats.

A study was carried out on 40 newborn rats to determine the effect of Gastrografin (a hyperosmolar solution, 1700 mosm/liter) on the gastrointestinal tract. All the newborns received an inoculum of Klebsiella bacteria to the gastrointestinal tract. Thirty received, in addition to maternal milk, a feeding of Gastrografin twice daily. The Gastrografin was found to cause severe and irreversible damage to the mucosa of the small intestine, causing the death of 24 rats less than a week after start of the experiment. The 10 rats who received no Gastrografin and served as controls showed no signs of disease or damage to the intestinal tract. Cultures taken from the peritoneal cavity after sacrifice were all positive for Klebsiella in the Gastrografin group (30 rats) and negative in the controls (10 rats). This study has therefore demonstrated that severe damage to the small intestine mucosa will lower the intestinal barrier and lead to transmural translocation of bacteria into the peritoneal cavity.

Animals↗

The development of vascular supply of normal rat prostate during the sexual maturation: an angiographic study.

Vascular distribution of small blood vessels and capillaries using India ink angiography was studied in normal rat prostate from puberty up to full sexual maturation. The study included both macroscopic observation of the lobular vascular irrigation and the histological assessment of the periacinar capillary network. The topographical distribution of the main prostate branches was found to be different among the rat prostate lobes. The ventral lobe seems to be better irrigated than the dorsal one. The former being supplied by two parallel vascular systems, one irrigating the median two-thirds of the ventral lobe, whereas the remaining external one-third was found to be conjointly irrigated from the pericapsular branches of the fat pads. The blood vessels of the dorsal and lateral lobes emerged radially from a periurethral circle, with the dorsal branches ending blindly in the connective tissue of the pelvic cavity, whereas the lateral prostate was also conjointly irrigated by a dual vascularization from the pericapsular fat pad and the periurethral circle branch. The histological study revealed quantitative differences between the periacinar capillaries of both ventral and dorsal lobes. The capillary density was found to be age dependent and directly proportional to the acinar size. Small acini were less well irrigated by capillaries than were the larger ones. The number of capillaries per acinar area increased progressively toward the maturation (day 90); thereafter, their number remained constant. Both prostate lobes showed identical patterns. The heterogeneous vascular networks among the rat prostatic lobes might offer an additional clue for their distinctive morphophysiological characteristics, which most probably play a role in various pathogenetic processes.

Angiography↗

Post-mortem changes in the normal rat carotid body: possible implications for human histopathology.

The carotid bodies in experimental animals contain only one variety of type I cells whilst in the human organ three varieties of this cell type have been described. We have examined the effects of post-mortem change on the structure of the type I cell of the rat carotid body. When the organ is examined immediately after death of the animal all of the type I cells exhibit similar morphology. With increasing delay in fixation of the tissue the type I cells undergo autolytic changes. Within 2 h of death the nuclei become hyperchromatic and the cytoplasm exhibits an increasing eosinophilia. In carotid bodies fixed 4 h post-mortem a further type I cell variant is seen in which the nucleus lacks a chromatin pattern and become pyknotic. We believe that previous descriptions of three varieties of type I cells in the human carotid body are based upon a description of post-mortem change. Furthermore, in any study of this highly oxygen dependent tissue it is essential that due account be taken of the delay between death and fixation.

Animals↗

Morphometric studies of pancreatic acinar granule formation in NCTR-Balb/c mice.

NCTR-Balb/c mice are afflicted with a cholesterol lysosomal storage disorder stemming from a defect in intracellular cholesterol processing. The clinical and biochemical abnormalities expressed in the mice resemble Niemann-Pick type C and D disorders in humans. One of the proposed mechanisms to explain the pathophysiology of the disorder implies a defect in the process of membrane transport that normally takes place in the vesicular movement of cholesterol to specific target sites in the cell. Secretory granule formation in pancreatic acinar cells is one of the biological processes known to involve massive membrane flow. Thus, we have undertaken a morphometric study of the regranulation mechanism in the pancreatic acinar cells of the mutant mice, as a way of studying cellular membrane movement. Electron micrographs of pancreatic acinar cells from mutant and normal mice were taken at several time points after extensive degranulation induced by pilocarpine injection. Two hours after stimulation the pancreatic cells demonstrated a complete loss of granules, and at later time points newly formed granules appeared. Identical unit granule volumes were observed in both groups, indicating that the progranules were of normal size. However, the rate of granule formation and maturation was reduced in the mutant mice, which might be the result of a defect in membrane function.

Animals↗

Immunohistochemical approach to the study of the cat carotid body.

The mammalian carotid body contains a number of different cell types which are not always easy to identify in routine histological sections. We have devised a battery of immunohistochemical tests which overcome this difficulty and offer the possibility of performing routine morphometric analyses of the response of the organ to various pathological processes in paraffin-embedded sections. The type 1 cells can be identified on the basis of their reaction with neuronal specific enolase, whilst type II cells react with antibodies to S-100 protein. Schwann cells do not react with S-100 antibodies but do so with antibodies to glial fibrillary acidic protein; nerve fibres can be identified by their reaction to neurofibrillary protein.

Animals↗

Immunocytochemistry of epithelial markers in citral-induced prostate hyperplasia in rats.

Immunocytochemical characterization of several epithelial markers using the PAP technique was analyzed during different stages of induced prostatic hyperplasia in rats. Intact adolescent rats (42 days old) were treated with citral (3,7 dimethyl-2,6 octadienal) for 10, 30 and 100 days and their ventral prostate compared to untreated, matched-age animals. Among the epithelial markers studied the prostatic specific acid phosphatase was present in hyperplastic prostates of rats. The immunoreaction showed a fair correlation with the severity of lesion and duration of treatment. The prostatic specific antigen showed equally immunoreactive in both control and treated rats. The hyperplastic and normal rat prostates did not show immunoreactivity towards the other epithelial cell markers such as epithelial membrane antigen, carcinoembrionic antingen and alpha-fetoprotein antisera. It is concluded that prostatic specific acid phosphatase, and to a lesser extent prostatic specific antigen, might represent valuable markers for comparative studies of prostatic hyperplasia in rodents.

Acyclic Monoterpenes↗