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PubMed1985

[Morphogenetic characteristics of the aggregates formed in epithelial and mesenchymal recombinations of the lungs from intact and urethane-exposed mouse embryos].

A study was made of the morphogenesis of organotypic aggregates obtained by epithelial mesenchymal recombinations from the lungs of embryonic mice, intact and treated with urethane. Normal growth and differentiation of organotypic structures were observed in long-term cultures of aggregates obtained by recombinations of the lung epithelium (E) and mesenchyma (M) from intact (i) embryonic mice (EiMi). Hyperplasia and squamous-cell metaplasia (with or without keratinization) of the epithelium were found in aggregates obtained from E and M of the treated mouse embryos (EtMt) and in aggregates obtained by recombinations of lung E and M from intact and treated embryos (EtMi, EiMt). The data obtained suggest that the alterations in epithelial mesenchymal interactions are of great significance for transplacental lung blastomogenesis and that the mesenchymal lung cells play an important part in mediation of the transplacental carcinogenous effects on epithelial target cells via subsequent epithelial mesenchymal tissue interactions.

Animals↗
PubMedDate not supplied

[Chemoreactive properties of medial thalamic neurons of the rat in the following states: urethane anesthesia, wakefulness and immobilization stress].

An analysis was carried out by means of microelectrode records and microionophoresis of medial thalamus neurones chemical sensitivity to acetylcholine and noradrenaline in rats under urethane anaesthesia, in free behaviour and in immobilization stress. Significant differences were observed in stability of cellular responses to repeated application of mediators under these conditions and in the correlation of the cells with qualitatively different reactions to these mediators. Along with the functional state of the animals, probability and direction of "spontaneous" changes of neuronal chemoreactive properties significantly depended on the type of sensibility inherent in them at that moment.

Acetylcholine↗
PubMed1979

Scanning electron microscope surface morphometry of type II alveolar lung cell response to urethane in strain A mice.

Quantitative scanning electron microscope (SEM) examination of the time course of type II cell hyperplasia in mice exposed to a single i.p. injection of urethane is presented. Counts of type II cells from random alveoli suggest that, compared to controls, a significant depression in type II cell numbers occurs during the first week, followed by a doubling in the next 3 to 4 week period. This supports conclusions of earlier studies done with thin sections and light morphometric techniques. The use of a SEM as the morphometric tool is statistically more efficient, however, since initial sample preparation is easier, samples are larger in area, resolution is higher and, most importantly, the amount of surface area available for examination is many times greater than that presented by light microscope examination of cross sections with equivalent magnification.

Animals↗
PubMed1984

Urethan-induced mammary tumorigenesis in a murine mammary tumor virus (MuMTV)-positive mouse strain: evidence for a keratinized nodule as an MuMTV-negative precursor lesion for squamous cell tumors.

Administration of urethan (CAS: 51-79-6; carbamic acid, ethyl ester) in the drinking water of breeding female mice of the murine mammary tumor virus (MuMTV)-positive DD/Tbr strain and the MuMTV-negative DDf strain induced so-called keratinized nodules, which were demonstrable in wholemount preparations of mammary glands. It also induced squamous cell tumors (also called adenoacanthoma) at an extremely early age. The keratinized lesions appearing in the lobular areas of the mammary glands showed heavy infiltration with lymphocytes and as such were very different from hyperplastic alveolar nodules, the preneoplastic lesions for adenocarcinomas. Immunoperoxidase tests with antibodies against the MuMTV revealed that positivity of normal mammary gland epithelium in the DD/Tbr strain was not found in the keratinized nodules, which was further evidence that in squamous cell tumorigenesis of the mammary gland the MuMTV is not expressed overtly even at an early stage in tumorigenesis, in contrast to the case with adenocarcinoma tumorigenesis. These findings substantiate previous conclusions that the MuMTV is not involved in chemical carcinogenesis of the mouse mammary gland.

Animals↗
PubMed1980

[Paramagnetic diethyleneimides of urethane phosphoric acids as antitumor agents].

Under study were paramagnetic diethylene imides of urethan phosphoric acids containing three type groups showing carcinostatic activity. There was found small toxicity and a wide spectrum of the antitumor effect of the compounds, also the correlation between the chemical structure and carcinostatic effect was investigated. The nitroxyl radical was shown to participate in the antitumor effect manifestation.

Animals↗
PubMedDate not supplied

[Spike activity of neurons of the medial thalamus of the rat during urethane anesthesia, wakefulness and immobilization stress].

A statistical analysis was carried out of unit activity in the medial thalamus (MT) of rats in states of urethane anaesthesia, quiet unrestrained wakefulness and immobilization stress. Discharge activity of MT neurones in these states significantly differed by parameters characterizing both single cells (mean frequency, standard deviation, variation coefficient) and their populations (intragroup variability of parameters, homogeneity of population as to the activity of its cells components, the extent of connections between them). The revealed differences are interpreted as a reflection of the properties of central interneuronal integration created in accordance with real needs of the organism for providing for its adaptive activity.

Anesthesia, General↗
PubMed1984

Localization of specific [3H]dexamethasone binding in urethan-induced mouse lung tumors.

Pulmonary tumors induced in A/J mice 14 months after a single i.p. injection of urethan vary greatly in size. Since glucocorticoids may play a major role in regulating lung cell proliferation, glucocorticoid binding was examined in these tumors to determine whether tumor size was related to any specific pattern of [3H]dexamethasone [( 3H]DEX) binding. Tumor samples were incubated in vitro with 17 nM [3H]DEX for 90 min at 37 degrees, washed extensively to reduce nonspecific binding, and either fractionated by differential centrifugation to quantify nuclear and cytosolic binding or processed for autoradiography. Quantitative binding studies demonstrate a reduction in specific nuclear [3H]DEX binding and an increase in nonspecific cytosolic binding in all of the tumors examined as compared to normal adult lung. Autoradiographic studies reveal pulmonary tumors of different morphology which vary in their [3H]DEX binding characteristics. Small tumors were of two histological patterns, alveolar adenomas which are probably derived from alveolar type II cells and papillary adenomas which are probably derived from bronchiolar Clara cells. The alveolar adenomas contain little nuclear [3H]DEX binding, whereas the papillary adenomas show extensive nuclear localization of [3H]DEX. These results indicate that nuclear localization of [3H]DEX can provide a biochemical criterion for distinguishing alveolar from papillary adenomas. Most of the larger tumors were either papillary or anaplastic in morphology and localized [3H]DEX in their nuclei. This suggests that these larger and possibly more malignant tumors are derived from papillary adenomas.

Animals↗
PubMed1978

[Lower urethane carcinogenicity for the lungs of thymus-free nude mice in comparison with immunologically normal littermate mice].

Lung adenomas arose in 2 of 10 nude mice injected twice with urethane in a dose of 1 mg/g of body weight; these tumours were revealed in 7 of 10 immunologically normal littermates treated in the same way. Mean adenoma numbers were 0.2 +/- 0.13 per nude mouse and 1.2 +/- 0.36 per normal mouse (P less than 0.05). The data obtained do not agree with the immunological surveillance concept which predicts greated number of tumours in the nude mice in comparison with the normal ones.

Adenoma↗
PubMed1980

Inhibition of urethan induced lung tumour growth in strain A mice by 5-methyl cytidine.

In two in vivo experiments, low doses of 5-methyl cytidine significantly suppressed the growth of urethan-induced lung tumours in strain A mice while higher doses were less effective. This inverse dose-response relationship mimics the previously reported effect of 5-methyl cytidine on mammary tumour growth in C3H mice. The finding that 5-methyl cytidine inhibits lung tumour growth as well as mammary tumour growth suggests this nucleoside may be an effective inhibitor of solid tumour growth in general. A study of the effect of 5-methyl cytidine on mouse lung tumour cell viability in vitro suggests that the direct cytotoxic effect of 5-methyl cytidine is dependent on the cell cycle. Since cell-cycle dependent agents do not inhibit lung tumour growth in vivo, 5-methyl cytidine probably inhibits mouse lung tumour growth indirectly by some effect on the host rather than by a direct cytotoxic effect on the lung tumour.

Adenoma↗
PubMed1994

[Phenothiazine derivatives, chlorpromazine and triflupromazine, produce different effects on sympathetic nerve activity in urethane-anesthetized rabbits].

UNLABELLED: This study was designed to evaluate effects of chlorpromazine (CPZ) or triflupromazine (TPZ) on renal sympathetic nerve activity and hemodynamics in urethane-anesthetized rabbits. METHODS: Thirty-five rabbits were divided into the following two groups: CPZ group (N = 10) and TPZ group (N = 25), challenged by an intravenous injection of either CPZ (0.4 mg.kg-1) or TPZ (0.2 mg.kg-1), respectively. Each experimental group was further divided into the following groups. CPZ group was divided into CPZ-INTACT group of animals with neuraxis intact (N = 6) and CPZ-SAD group of animals with combined denervation of the carotid sinus and aortic nerves (N = 4). TPZ group was divided into TPZ-INTACT group of rabbits with neuraxis intact (N = 8), TPZ-VAGOTOMY group of only cervical vagotomy (N = 6), TPZ-SADV group with combined denervation of the carotid sinus and aortic nerves with cervical vagotomy (N = 5) and TPZ-VI group with right cervical vagotomy but having the intact left vagus (N = 6). In the last group, right afferent vagal nerve activity was measured simultaneously. Mean blood pressure, central venous pressure, heart rate and renal sympathetic nerve activity were measured at the same time. RESULTS: In the CPZ-INTACT group, the agent caused a decrease in mean blood pressure and significant increases in sympathetic nerve activity and heart rate, but no significant change in central venous pressure. This increase in sympathetic nerve activity and heart rate disappeared in the SAD animals in spite of hypotension. Animals of the TPZ-INTACT group showed an abrupt decrease in sympathetic nerve activity in response to hypotension, but did not exhibit a remarkable change in heart rate and central venous pressure. However, in contrast, animals with severed cervical vagi showed a sympathetic augmentation after the TPZ injection. These sympathetic changes were abolished in the SADV animals. In the TPZ-VI group, TPZ elicited a decline in sympathetic nerve activity similar to that observed in INTACT animals, but afferent vagal nerve activity increaed simultaneously with sympathetic depression. CONCLUSION: These results indicate that a reflex increase in sympathetic nerve activity which occurred during hypotension after CPZ injection may have been mediated by the arterial baroreceptor reflex and that a sympathetic reduction after TPZ administration may have resulted from a reciprocal interaction between an excitation through the sino-aortic nerves and an inhibition via the vagal nerves.

Anesthesia↗
PubMed1993

[Effects of air injection on hemodynamics and sympathetic nerve activity in urethane-anesthetized rabbits].

We designed this experiment to evaluate effects of intravenous bolus injection of air (0.5 ml.kg-1) on systemic blood pressure (SBP), central venous pressure (CVP), and renal nerve activity (RNA) in urethane-anesthetized rabbits. Animals were divided into the following three groups: animals with neuraxis intact (I group, N = 5), cervical vagotomized animals (V group, N = 5) and sinoaortic denervated animals (SAD group, N = 4). All animals were placed on the right-side down position to avoid effects of the posture throughout the experiments of air embolism. In the I group, air caused profound hypotension (from 95 +/- 10 to 54 +/- 15 mmHg) associated with a significant increase in CVP (from 2 +/- 2 to 7 +/- 3 mmHg) twenty seconds after the injection of air. In spite of the significant hypotension, RNA response did not show any increase for twenty seconds. This response was followed by an augmentation in RNA thirty seconds after air injection. In contrast, vagotomized animals exhibited a significant RNA increase (147 +/- 11% of the control) in response to a decrease in SBP (from 93 +/- 6 to 78 +/- 5 mmHg) and an increase in CVP ten seconds after the administration of air. In SAD group, a rapid and remarkable decline in SBP (from 85 +/- 13 to 47 +/- 12 mmHg) occurred ten seconds after the injection of air. Despite this hypotension, RNA decreased nearly to a noise level after administration of air.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1976

Induction of type B virions to bud into cytoplasmic vacuoles in a mammary tumor of an X-ray- and urethan-treated X/Gf mouse.

Electron microscopic studies of thin sections of a mammary carcinoma that developed in a female mouse of the syngeneic X/Gf low-cancer strain after treatments with X-rays (3 X 100 rads weekly) followed by 8 weekly i.p. injections of urethan (1 mg/g body weight) revealed extensive budding of B particles into cytoplasmic vacuoles and numerous characteristic B virions in the vacuolar lumens. Simultaneous budding of B particles into cytoplasmic vacuoles and budding of B particles at plasma membranes of the same cancer cell were also noted (figs. 2 to 6).

Adenocarcinoma↗
PubMed1998

Adsorption of proteins onto poly(ether urethane) with a phosphorylcholine moiety and influence of preadsorbed phospholipid.

In a previous report we demonstrated that the blood compatibility of poly(ether urethane) (PEU) was improved by grafting phosphorylcholine (PC) groups on the surface. The improved blood compatibility was indicated by decreased platelet adsorption/activation and reduced thrombin formation at the polymer surface in experiments in which the surfaces were contacted with platelet-rich plasma in vitro. In the present study, we investigated the effect of grafted PC groups at a PEU surface on protein and phospholipid adsorption. Adsorption of human fibrinogen (Fg), human serum albumin (Alb), human high-molecular-weight kininogen (HMWK), and dioleoyl phosphatidylcholine (DOPC) vesicles was measured by ellipsometry. For this purpose, thin PEU films were cast on silicon wafers. The polymer film was photochemically modified with a PC-containing aryl azide. The presence of PC groups on the polymer surface was demonstrated by ESCA (Electron Spectroscopy for Chemical Analysis). The hydrophilicity of the polymer surface increased by the surface modification, as indicated by a decrease of the contact angle from 59 degrees before to 43 degrees after modification. Our data show that the presence of PC groups has little effect on the adsorption of proteins to a PEU surface. The highest adsorption was observed for Fg (0.49 microgram/cm2 on PC-modified PEU and 0.50 microgram/cm2 on PEU), followed by HMWK (0.28 microgram/cm2 on both PC-modified PEU and PEU), and Alb (0.16 microgram/cm2 on PC-modified PEU and 0.18 microgram/cm2 on PEU). Protein adsorption was further studied on a "biomembrane-like" DOPC bilayer formed on hydrophilic silicon. We found no protein adsorption on this DOPC bilayer. The adsorption of small unilamellar DOPC vesicles on the polymer surfaces amounted to about 0.06 microgram/cm2 (corresponding to circa 30% of monolayer coverage) and was similar for PC-modified PEU and PEU. Despite this partial surface coverage, preadsorbed DOPC on the polymer surface diminished the subsequent adsorption of proteins considerably. These results show that the mere presence of phosphorylcholine groups on a PEU surface is insufficient to suppress protein adsorption. The highly ordered structure of natural phospholipid bilayers seems to be required to suppress protein adsorption effectively.

Adsorption↗
PubMed1998

Effects of curing time and filler concentration on curing and postcuring of urethane dimethacrylate composites: a microcalorimetric study.

The isothermal enthalpy changes with time of a dental composite were examined by microcalorimetry to isolate the effects of different filler concentrations and curing times on chemical aging of these composites. Urethane dimethacrylate (UDMA) monomer, zirconia-silica (ZS) powder, and 3-methacryloxypropyltrimethoxysilane (MAPM) were used as organic and inorganic matrices, and a coupling agent, respectively. The composite was mixed in different ratios and cured by visible light. The enthalpy changes with time for 0, 15, 45, 75% ZS-filled UDMA and 75% MAPM-silanated ZS-filled UDMA cured for 13, 30, 90, 150, and 300 s were measured at 37.0 degrees, 57.0 degrees, and 65.5 degrees C until equilibrium. Increased curing time and filler concentration caused the excess enthalpy changes (dH) and their rate of change (dH/dt) to increase with annealing time and apparent equilibrium was reached faster. In addition, dH showed nonlinear dependence with the increase in filler concentration by showing a maxima for samples containing 25 wt% filler. Further, filler silanation caused dH/dt to increase and required shorter times to reach apparent equilibrium. dH also reached a minimum when samples contained silanated filler, compared to composites containing unsilanated filler. It was concluded that the shorter curing time caused the occurrence of spontaneous densification, which facilitated continual resin curing; and longer curing time caused higher crosslinking of the organic phase. Moderate concentration of inorganic phase restricts the molecular motion of the surface layer of polymer onto filler particles, and the polymer is regarded as highly crosslinked, while a higher filler concentration forms aggregates that are covered by the polymer which causes a decrease in the molecular packing of the resin, and is reflected as low enthalpy values. Finally, silanation of the filler showed a highly endothermic reaction that is probably due to breaking and forming of bonds at the interface between the organic and the inorganic phases in the composites.

Calorimetry↗
PubMed1983

N-monosubstituted urethanes and esters of 6-cis-dimethylamino-1,3,3-trimethyl-2-oxabicyclo-[2.2.2]octan-5-trans-ol with hypotensive and other activities.

The synthesis of 6-cis-dimethylamino-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5-trans-ol (III) starting from 1,3,3-trimethyl-6-nitrimino-2-oxabicyclo[2.2.2]octane is described. Starting from aminoalcohol (III), a series of N-substituted urethanes (IV) and esters (V), as well as the rigid analogue of acetylcholine (VII), were prepared. A number of compounds (V) and particularly (IV) showed remarkable hypotensive and bradycardic activities in rats, whereas the p-aminobenzoate (V h) showed infiltration anesthesia in mice comparable to that of lidocaine. Antiarrhythmic activity in mice and antiacetylcholine activity in vitro are also reported.

Acetylcholine↗
PubMed1984

Esters and N-substituted urethanes of 6-cis-dimethylamino-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-5-cis-ol with hypotensive and other activities.

The synthesis of 6-cis-dimethylamino-1,3,3-trimethyl-2-oxabicyclo [2.2.2] octan-5-cis-ol (III) starting from 6-cis-dimethylamino-1,3,3-trimethyl-2-oxabicyclo [2.2.2] octan-5-trans-ol (I) is described. Starting from aminoalcohol (II), a series of esters (IV) and N-substituted urethanes (V) was prepared. Benzoate (IV e) showed a remarkable hypotensive and bradycardic activity in rats, whereas acetate (IV a) showed infiltration anesthesia and antiarrhythmic activity in mice slightly inferior to those of lidocaine. Antiacetylcholine activity in vitro is also reported.

Acetylcholine↗
PubMed2002

Fluorinated surface-modifying macromolecules: modulating adhesive protein and platelet interactions on a polyether-urethane.

Polyether-urethanes (PEUs) have been the materials of choice for the manufacture of conventional blood-contacting devices. Nevertheless, biostability and blood compatibility are still among the principal limitations in their long-term application. Studies investigating the development of protective coatings for PEUs have shown that degradation can be reduced with the use of fluorinated surface-modifying macromolecules (SMMs). It has also been hypothesized that SMM-modified PEU surfaces may exhibit improved blood compatibility because other studies have shown a modulation in fibrinogen adsorption onto these surfaces. To determine the blood compatibility of a PEU-containing fluorinated SMMs, a series of in vitro experiments were designed to study the pattern of protein adsorption from plasma and then to assess the nature of platelet adhesion and activation on each substrate. Western blot analysis as well as single protein studies revealed that the dominant "adhesive proteins" [fibrinogen (Fg), fibronectin (Fnc), and vitronectin (Vnc)] were adsorbed on two of the SMM-containing PEUs in lower amounts relative to unmodified base. Platelet adhesion and activation data further highlighted the differences among the various substrates. It was shown that the unmodified base had a higher number of adhered platelets relative to the SMM-modified surfaces, and that of the SMM-containing substrates, which showed the lowest levels of adhesive proteins also, exhibited significantly lower platelet densities. Close morphological examination further revealed that platelets residing on these latter substrates were not appreciably activated. Based on the current evidence, it is believed that the fluorinated SMMs demonstrate good potential for the development of surfaces with minimal thrombogenic character in in vivo applications.

Adsorption↗
PubMed2002

Synthesis, characterization, and cytocompatibility of elastomeric, biodegradable poly(ester-urethane)ureas based on poly(caprolactone) and putrescine.

The engineering of tissue for mechanically demanding applications in the cardiovascular system is likely to require mechanical conditioning of cell-scaffold constructs prior to their implantation. Scaffold properties amenable to such an application include high elasticity and strength coupled with controllable biodegradative and cell-adhesive properties. To fulfill such design criteria, we have synthesized a family of poly(ester-urethane)ureas (PEUUs) from polycaprolactone and 1,4-diisocyanatobutane. Lysine ethyl ester (Lys) or putrescine was used as chain extenders. To encourage cell adhesion, PEUUs were surface modified with radio-frequency glow discharge followed by coupling of Arg-Gly-Asp-Ser (RGDS). The synthesized PEUUs were highly flexible, with breaking strains of 660-895% and tensile strengths from 9.2-29 MPa. Incubation in aqueous buffer for 8 weeks resulted in mass loss, from >50% (Lys chain extender) to 10% (putrescine chain extender). Human endothelial cells cultured for 4 days with medium containing the degradation products from PEUUs with either the Lys or putrescine chain extender showed no toxic effects. Cell adhesion was 85% of that measured on tissue-culture polystyrene for unmodified PEUU surfaces (p < 0.01) and >160% (p < 0.001) of polystyrene on RGDS-modified PEUUs. These biodegradable PEUUs demonstrate potential for future application as cell scaffolds in cardiovascular tissue-engineering or other soft-tissue applications.

Absorbable Implants↗