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Inhibition of galactosamine induced edemas in the rat by drugs preventing macromolecular leakage from the hamster cheek pouch microvasculature.

We have shown that terbutaline and dimethpyrindene, 2 drugs which prevent macromolecular leakage in the in vivo--bio-assay of Hamster Cheek Pouch, either by direct action onendothelial cells or by blocking histamine receptors at the microvascular leakage sites, can also prevent macromolecular leakage in vivo in 2 different models of generalized edema.

Animals↗

Microvascular changes due to repeated local pressure-induced ischemia: intravital microscopic study on hamster cheek pouch.

Pressure ulcer and tracheal injury occurring after endotracheal intubation are clinical examples of pressure-induced tissue damage where magnitude and duration of the applied pressure are of major importance. The objective of this study was to investigate the efflux of macromolecules caused by repeated short-time ischemia induced by a pressure of 60mmHg, which causes circulatory standstill. Pressure was applied to the hamster cheek pouch and the efflux of the macromolecules of the microvasculature was evaluated by using the fluorescein isothiocyanate (FITC) dextran dye and intravital microscopy. The pressure was applied for either 1 or 5 min and repeated 8 times with a 10min restitution period in between. The repeated 1min pressure caused almost no change in microvascular efflux of FITC-dextran while 5min repeated pressure did. The gross mechanical impact on the tissue seems to be equal in the 1 and 5min exposure and thus cannot explain the difference in the developed permeability. Ischemia of such short time as 1 and 5min does not alter the energy state of the tissue significantly. The reactive hyperemia and the mediating vasoactive amines can differ markedly after 1 and 5min ischemia and can thus contribute to the permeability alteration. However, the role of vasoactive amines is unclear and further experiments are needed to determine their role.

Animals↗

Beta-endorphin. Vasodilating effect on the microcirculatory system of hamster cheek pouch.

beta-Endorphin, enkephalins and morphine dilated in vivo the arteriole of the microcirculatory system in hamster cheek pouch. beta-Endorphin had the highest potency and morphine the lowest. The effect was dose dependent and blocked competitively by the opiate antagonist, naloxone. The result demonstrated an effect of the opiates on the arteriole of the cutaneous circulation. This effect probably plays an important role in thermoregulation.

Animals↗

[Dirofilariasis in humans. Report of a case with localization in the cheek (author's transl)].

Cutaneous dirofilariasis usually affects animals (dogs and cats) but can occur in human-beings. Occasionally, this cosmopolitan disease is seen in France. Our case-report is the sixteenth registered in France. The patient, a forty-two-year-old man, was infected in Corsica. He presented with a tumor of the right cheek from which a pregnant adult Dirofilaria (Nochtiella) repens was extracted.

Adult↗

Promotion of benign hyperplastic lesions by calcium, magnesium and cAMP, and inhibition of tumor progression by magnesium in hamster cheek pouch.

Ca, Mg (0.1 or 0.2M) and ionophore A23187 (10(-5) - 10(-4)M) promoted benign hyperplastic lesions (BHLs) to a highly variable degree when applied topically in hamster cheek pouch after initiation with 7, 12-dimethylbenz(a)anthracene (DMBA). The changes in the promoting effects of Ca and Mg between experiments were not parallel. Mg but not Ca inhibited retinyl acetate-induced progression of BHLs to advanced tumors. Cyclic adenosine 3',5'-monophosphate (cAMP) (10(-5) - 10(-3)M) promoted BHLs. The results are discussed in terms of possible mechanisms involved.

9,10-Dimethyl-1,2-benzanthracene↗

Stereological studies of differentiation in hamster cheek pouch epithelium: variations in the volume and frequency of mitochondria.

The present report describes quantitative studies of mitochondria from stratified squamous epithelial cells from hamster cheek pouch mucosa in differentiating compartments. Mucosa was processed for electron microscopy and, using strict sampling procedures, electron micrographs of epithelium from defined basal, spinous and granular strata were acquired. Using stereological and other morphometric methods, the volume density, numerical density and volume-to-surface ratio of mitochondria were estimated in each cellular layer, and these data were transformed into absolute values characterising the average cell in these layers. The results suggest that both volumetric and numerical densities of mitochondria decreased progressively during epithelial differentiation; conversely, the total volume and number of mitochondria present in granular cells were consistently higher than in basal cells, as was the volume of individual mitochondria. These quantitative changes may reflect functional alterations in the metabolism of epithelial cells during differentiation and provide a base line for further work on experimental epithelial biology and pathology.

Animals↗

Morphological and functional aspects of heart homograft adaptation to hamster cheek pouch. Spontaneous pulsatile activity and ultrastructure.

Atrial homografts from newborn hamsters, transplanted into cheek pouches of adult Syrian golden hamsters, were studied using intravital and electron microscopy. Half of the transplants survived up to 1 year, performing spontaneous pulsatile activity. The transplants could be influenced by beta-receptor activating or blocking substances applied intravenously to the host animal. For morphological analysis homografts were taken 3, 6, and 12 months after transplantation. Irregular arrangement of the myofibers occurred, and the T system was seen to be replaced by plasmalemmal and sub-plasmalemmal vesiculations. There was some evidence for hypoxia in the grafts. Dedifferentiation of atrial cardiocytes, somehow resembling smooth muscle cells, is discussed. Despite these morphological changes the specific contractile function of the grafts was preserved.

Animals↗

Dose response effect of retinyl acetate on DMBA induced carcinogenesis in the hamster cheek pouch.

The role of vitamin A in the induction and growth of chemically induced tumors is still controversial. While in some studies vitamin A influenced inhibition of chemically induced tumors was observed, other studies report on an enhancing influence of this substance on tumor induction. The cheek pouch epithelium of sixty five Syrian golden hamsters was exposed to DMBA and different doses of retinyl acetate, singly and in combination with DMBA. The findings suggest that 1) a significant delay occurs in tumor induction in animals treated with DMBA in combination with a higher concentration (2.0%) of retinyl acetate, 2) retinyl acetate at lower concentration (0.5 and 1.0%) does not inhibit or delay tumor induction.

9,10-Dimethyl-1,2-benzanthracene↗

Hamster cheek pouch as a bioassay system in short term screening for tumor initiating and promoting agents. Optimization of parameters and observations of effects of cytotoxicity on tumor promotion by retinyl acetate.

The effects of various conditions on tumor initiation by 7,12-dimethylbenz(a) anthracene (DMBA) and promotion by retinyl acetate (RA), both in dimethylsulfoxide, were studied by topical application in hamster cheek pouch. The variables studied were: initiation and promotion time and schedule (alternate vs consecutive day paintings), concentration of DMBA used for initiation, and cytotoxicity. Spontaneous tumor progression followed by regression was observed in control animals which had been initiated for 4 weeks with 0.2% DMBA, but not given subsequent promotion treatment. Spontaneous progression was not observed in control animals which had been given only 2 weeks of initiation treatment, although RA both promoted new tumors and caused progression of benign hyperplastic lesions (BHLs) to advanced tumors. The approximate optimal conditions for obtaining acceptable tumor yields from promotion while minimizing associated errors and time periods were: 2 weeks of initiation with 0.2% DMBA and 4 weeks of promotion with 0.05 M RA, both with alternate day painting schedules. Reducing the initiation period but painting on consecutive days caused intolerable cytotoxicity and lowered tumor yields although the total dose of DMBA was kept constant. Increasing initiation time increased tumor yield in unpromoted controls as well as promoted groups, thus increasing errors in net yield from promotion. Similar results were obtained from doubling concentration of DMBA and halving initiation time. Reducing promotion time to below 4 weeks lowered tumor yield due to insufficient time for tumor development. Increasing promotion time to 6 weeks lowered tumor yield in both control and promoted groups, possibly due to spontaneous regression. Cytotoxicity enhanced progression to advanced tumors all of which were inflamed polypoid fibrovascular lesions. The cytotoxicity of DMBA was far greater than that of RA. Evidence is presented that tumor promotion by RA is not due to cytotoxicity. The hamster pouch system may afford an excellent short term mammalian screening test for tumor initiating and promotion agents.

9,10-Dimethyl-1,2-benzanthracene↗

Volumetric alterations in tonofibrils during epithelial differentiation in hamster cheek pouch mucosa.

The present report describes the use of stereological procedures to evaluate the volume of tonofibrils present in defined epithelial strata undergoing differentiation. Hamster cheek pouch epithelium was processed for electron microscopy and, following strict sampling procedures, micrographs were obtained from basal, spinous and granular layers. Using stereological point counting techniques, the volume density of tonofibrils present in unit volume of epithelial cytoplasm was determined for each layer. From previously determined estimates of cytoplasmic volume in this tissue, it was possible to calculate the absolute volume of tonofibrils present in the 'average' epithelial cell of each layer. The results describe essentially similar volume density data for each of the layers investigated. However, estimates of tonofibril volume in the 'average' cell increase more than threefold between basal and granular layers. It is concluded that as the epithelial cell differentiates through spinous and granular strata, synthesis of tonofilaments may occur.

Animals↗

Carcinoembryonic antigen from human malignant melanoma cells. II. Grafting of the cells in the hamster cheek pouch.

The preceding paper described production and release of carcinoembryonic antigen (CEA) by in vitro culture of the human malignant melanotic melanoma (HMMC-ShAE+) cell line; the present paper reports on two findings related to CEA biofunction. 1) The function of cell membrane oligosaccharides on the antigen-antibody reaction, i.e. the binding of 125I-labelled monoclonal anti-HMMC-ShAE+ antibodies to enzymically modified HMMC-ShAE+ cells. In these experiments, two approaches were used: sequential treatment with exohydrolases and cultivation of the cells in media supplemented with nontoxic levels of tunicamycin and swainsonine. 2) The effect of grafting, into the hamster cheek pouch, of modified HMMC-ShAE+ cells on plasma CEA, plasma anti-CEA and antibody-dependent cell-mediated cytotoxicity. Commercially available 125I-labelled CEA and the "Abbott" enzyme-linked immunoassay were used to monitor plasma anti-CEA and CEA levels, respectively. 125I-deoxyuridine-labelled HMMC-ShAE+ were used to monitor plasma antibody-dependent cell-mediated cytotoxicity.

Animals↗

[Complex receptor formations of the cheek pouch of the golden hamster].

In the golden hamster the cheek pouch receptory apparatus presented by a peculiar form of complex sensitive terminals has been studied. Every terminal is a combination of several compact bushes overlapping each other. All the bushes are formed with separate myelin fibers. The fibers participating in the formation of the complex receptor can reach 4 in number, but more often there are 2-3 of them. The end-plates of the receptors are polymorphous formations with a maximal transversal section area equal to 0.5-16 mcm. When the bodies are intravitally stained with methylen blue, heterochromity of the end-plates is revealed. The complex receptory formations are supposed to be mechanoreceptors.

Animals↗

Promotion of benign hyperplastic lesions in hamster cheek pouch by membrane labilizing agents and calcium ion: evidence that intracellular calcium-induced release from growth control is an obligatory preliminary stage of tumor promotion.

Ca ion, ionophore 23187 and the membrane labilizing agents triton X-100, trypsin and phospholipase C promoted benign hyperplastic lesions (BHLs) but only rarely advanced tumors in hamster cheek pouch mucosa, which had been initiated with 7,12 dimethylbenz (a) anthracene. Retinyl acetate (RA) and croton oil markedly promoted both BHLs and advanced tumors. These results suggest that pathways modulated by intracellular Ca cause initiation-stabilized release from growth control, thus the promotion of BHLs, whereas additional mechanisms are required for the progression of BHLs to more advanced tumors. Some Ca-modulated systems which could be involved in promotion of BHLs are discussed in the light of published literature.

9,10-Dimethyl-1,2-benzanthracene↗

Histological and ultrastructural morphology of 7,12 dimethylbenz(alpha)-anthracene carcinogenesis in hamster cheek pouch epithelium.

The epithelial changes observed during hamster cheek pouch-DMBA carcinogenesis were classified as hyperplasia, dysplasia and carcinoma stages; carcinomas were usually well differentiated. During carcinogenesis, epithelial thickness increased and in dysplasia and carcinoma stages superficial cells exhibited a marked shift from ortho- to parakeratinization. Marked changes in intercellular organelles were observed and intracellular spaces increased progressively in size. Desmosomes were less commonly seen during carcinogenesis whereas the frequency of gap junctions appeared to increase. The epithelial-connective tissue junction exhibited prominent changes with increasing irregularity, discontinuity and duplication of the lamina densa and a decreasing frequency of hemidesmosomes. Cytoplasmic processes, some containing lysosomal dense bodies, often passed through breaks in the lamina densa and extended into a relatively structureless connective tissue. The results are discussed in relation to the changes in cellular organelles occurring in abnormal epithelial differentiation mediated by the carcinogen and to possible factors which might be involved in the process of cellular invasion.

9,10-Dimethyl-1,2-benzanthracene↗

Intra-uterine healing of fetal rat cheek wounds.

Cheek wounds, involving skin, mucosa, and muscle, were surgically created in utero on Sprague Dawley rat fetuses at 19 1/2 days gestation. Fifty fetuses were used in the study. Twenty-five fetuses were in the experimental group and 25 in the control. Five fetuses in each group were sacrificed at 0, 6, 12, 18 and 24 hours post-operatively. Serial histological sections in the coronal plane were stained with haematoxylin and eosin. Restoration of continuity and primary epithelialisation of the oral mucosal and skin surfaces of the wound was observed to occur within 24 hours. The continuity of the muscle layer was not restored, but some mitoses were seen in the myeloblasts. There was a complete absence of acute inflammatory cells, and there was no scab formation. Healing occurred without scarring. These findings are discussed in comparison to previous findings on orofacial fetal wound healing (Goss 1976) and in regard to future prospects in intraceptive fetal surgery for the correction of deformities, in particular cleft lip.

Animals↗

Vasoconstrictor response of arterioles of the hamster cheek pouch to norepinephrine, prostaglandin H2, F2 alpha and carbocyclic thromboxane A2, a possible thromboxane A2 analogue.

Activated platelets produce thromboxane A2, a potent vasoconstrictor, which may play an important role in pathophysiological disturbances of microcirculation. Thromboxane A2 has a very short half life and has neither been isolated nor synthesized. Hence, the recently reported stable analogue, carbocyclic thromboxane A2 (CTA2), may become an interesting tool in pharmacological research. Its vasoconstrictor potency was compared in vivo with norepinephrine, prostaglandin H2 and F2 alpha using the following method: vessels of a hamster cheek pouch preparation were exposed to a superfusion to which the respective compounds were added to give 1 ng/ml to 0.1 mg/ml final concentrations. The decrease of vessel diameters was measured microscopically. Prostaglandin H2 was found to be the most potent vasoconstrictor followed by CTA2 and norepinephrine. Prostaglandin F2 alpha was least effective. The respective maximal vasoconstrictory responses did not differ significantly.

Animals↗