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PubMed1993

Phase studies of a urethane model compound and polyether macroglycols by infrared spectroscopy and the relationship between eutectic composition of soft segment and blood compatibility.

The binary mixtures of a urethane model compound, diethyl 4,4'-methylenebis(N-phenylcarbamate) (MDU), and various polyether macroglycols have been investigated mainly by infrared (IR) spectroscopy. The mixtures of macroglycol and MDU showed two C=O bands (free C=O at higher wave number, hydrogen bonded C=O at lower wave number), and the intensity of free C=O increased while that of hydrogen bonded C=O decreased linearly with increasing molar ratio of macroglycol/MDU. The slope of the increase or decrease suddenly changed at the specific molar ratio around the eutectic composition. The eutectic molar composition for PTMO1000/MDU was determined as 1.15 or 1.1 by differential scanning calorimetry (DSC) or infrared (IR) studies while that for PTMO3000/MDU as 0.345 or 0.55 by DSC or IR, respectively. The eutectic compositions for other sets were determined by IR studies as follows: PEO1000/MDU, 0.4; PEO3000/MDU, 0.16; PPO1000/MDU, 1.4; PPO3000/MDU, 0.45. The number of ethylene oxide, tetramethylene oxide, and propylene oxide units to form a eutectic with MDU calculated from these values were 15-20, 10-11, and 23-24, respectively. The similar DSC or IR changes were observed in the various kinds of polyurethanes such as MDI/BD, MDI/PTMO/BD, and MDI/PTMO polymers. The relationship between the eutectic compositions of soft segments (MDI/macroglycol) and the ideal Mn of the macroglycols in blood compatibility of segmented polyurethanes are discussed.

Benzyl Compounds↗
PubMed1990

Specific Ki-ras codon 61 mutations may determine the development of urethan-induced mouse lung adenomas or adenocarcinomas.

In A/J strain mice, the carcinogen urethan induces lung adenomas and adenocarcinomas that contain Ki-ras-activating mutations primarily in codon 61. These mutations affect the middle adenine in codon 61 resulting in the substitution of either arginine (AT----GC transition) or leucine (AT----TA transversion) for the wild-type glutamine. To analyze the expression of the wild-type and mutant Ki-ras mRNAs in primary mouse lung tumors and transformed mouse lung cell lines, we utilized reverse transcription of total mRNA and DNA amplification by the polymerase chain reaction. The wild-type allele of codon 61 was expressed in all normal lung and primary tumor samples and in all transformed cell lines, except one. Significantly, the leucine-substituted allele was expressed primarily in very small lung adenomas, whereas the arginine-substituted allele was expressed in large lung adenocarcinomas and transformed lung cell lines. The relative amounts of expression of the mutant versus wild-type Ki-ras alleles and the total Ki-ras mRNA expression was similar in both lung adenomas and adenocarcinomas. Further, the arginine mutant allele was present in adenocarcinomas having either alveolar or papillary tumor morphologies. These results suggest that the specific activating Ki-ras mutation is more critical to either lung adenoma or adenocarcinoma development than is the tumor's cell of origin or the extent to which the mutant alleles are expressed. A distinct role of the specific activating Ki-ras mutations in affecting lung tumor growth or malignant potential is indicated.

Adenocarcinoma↗
PubMedDate not supplied

The use of N-urethane-protected N-carboxyanhydrides (UNCAs) in amino acid and peptide synthesis.

N-Urethane-protected N-carboxyanhydrides (UNCAs) are very reactive amino acid derivatives. They have been successfully used in peptide synthesis, in both solution and solid phase. We have demonstrated that UNCAs are interesting starting materials for the synthesis of various amino acid derivatives. Chemoselective reduction of UNCAs with sodium borohydride led the corresponding N-protected beta amino alcohols. Reaction of UNCAs with Meldrum's acid, followed by cyclisation, yielded enantiomerically pure tetramic acid derivatives. Diastereoselective reduction of tetramic acid derivatives produced [4S,5S)-N-alkoxycarbonyl-4-hydroxy-5-alkylpyrrolidin-2-ones derived from amino acids, which after hydrolysis yielded statine and statine analogues. Tetramic acid derivatives could also be obtained by reaction of UNCAs with benzyl ethyl malonate in the presence of sodium hydride to yield gamma-N-benzyloxycarbonylamino-beta-oxodicarboxyl esters followed by hydrogenolytic deprotection and decarboxylation. UNCAs also reacted with phosphoranes to produce the ketophosphorane in excellent yields. Subsequent oxidation with oxone or with [bis(acetoxy)-iodo]-benzene produced vicinal tricarbonyl derivatives. These reactions usually proceeded smoothly and with high yields.

Amino Acids↗
PubMed1991

Comparative study of the effects of tianeptine and other antidepressants on the activity of medial septal neurons in rats anesthetized with urethane.

Tianeptine is a tricyclic antidepressant which enhances serotonin uptake in certain brain areas. Tianeptine has been reported to improve both working and reference memories in rodents. The effects of tianeptine on the spontaneous activity of medial septal neurons were studied in rats anesthetized with urethane. Systemic administrations (0.2-1 mg/kg i.v.) of tianeptine decreased the spontaneous activity and disorganized or suppressed the rhythmically bursting activity of medial septal neurons, in a dose related manner. Iontophoretic administrations of tianeptine did not modify the spontaneous activity of medial septal neurons. Changes of the bursting activity were inconsistent. However, tianeptine blocked partially or completely the inhibition induced by the serotonin in 68% of the cases. In contrast, other antidepressants (amitriptyline, clomipramine and fluoxetine) potentiated the inhibitory effect of serotonin in 50%-60% of the cases. Our results show that tianeptine, applied by iontophoresis, has an effect on the medial septal neurons which was opposite to that of other antidepressants. On the basis of our findings, it can be tentatively proposed that tianeptine may have a beneficial effect on memory by counteracting the serotonin-induced inhibition of medial septal neurons.

Animals↗
PubMed1995

Morphological changes and proliferative activity of alveolar epithelium in mouse lungs treated with urethan.

We have observed sequential cellular changes in type II pneumocytes in mouse lungs following oral administration of 0.1% urethan solution. Histologically, scatterings of swollen alveolar cells were first noticed 25 days after administration. These cells continued to swell further, after which they aggregated more compactly to form a papillary structure by day 75. After day 100, distinct tumour nodules were found with atypical large cells in some areas. Necrotic foci appeared in large tumours of more than 4 mm diameter. At day 250, nucleoli became distinct and large bizarre and multinucleated cells were intermingled with some mitotic figures. These morphologies correspond to conventional descriptions; that is, hyperplasia (day 25-75), benign neoplastic changes (day 75-100) and malignant neoplastic changes (day 100-250). The proliferating cell nuclear antigen (PCNA) and nucleolar organizer regions (AgNOR) scores in these lesions increased with time, and proliferative activities during tumour progression seemed continuous. However, proliferative activity of the cells on specific days did not differ statistically from the values on neighboring days. We speculate that the hyperplasia-like lesions seen in our mice are neoplastic in nature from their outset.

Animals↗
PubMed1990

Firing relations of lateral septal neurons to the hippocampal theta rhythm in urethane anesthetized rats.

The firing of lateral septal neurons was examined in relation to the hippocampal theta rhythm in urethane anesthetized rats. In general, the firing rates of these cells were low during both theta and non-theta EEG states. There was no significant change in firing rate between the two states (theta: 8.5 +/- 9.9 spks/sec; non-theta: 6.0 +/- 5.3). Sixty-four of 68 cells fired simple spikes and 4 cells were found to fire bursts of action potentials (complex-spikes). Approximately 30% (21/65) of the cells showed a significant phase relation to the hippocampal theta rhythm. The preferred phases of firing of these 21 cells were broadly distributed. The possibility that the phase-locked firing of LSN cells is due to the phase-locked firing of hippocampal projection cells is discussed.

Action Potentials↗
PubMed1996

Intraseptal infusion of selective and competitive glutamate receptor agonist NMDA and antagonist D-2-amino-5-phosphonopentanoic acid spectral implications for the physostigmine-induced hippocampal theta rhythm in urethane-anesthetized rats.

Theta (theta) rhythm may be mediated, at least in part, by a glutamate neurotransmitter. Thus, in the present study, it was hypothesized that the septum glutamatergic NMDA receptor subtype may be involved in the modulation of physostigmine-induced theta rhythm. To test this hypothesis, we analyzed, in the urethane-anesthetized rat, the effects of septum application of NMDA and D-2-amino-5-phosphonopentanoic acid (AP5), selective and competitive NMDA agonist and antagonist, respectively, on the spectral characteristics of hippocampal theta rhythm elicited by intravenous injection of a anticholinesterase agent, physostigmine. A low dose (16 nmol) of AP5 did not significantly affect EEG recordings, whereas a high dose (50.75 nmol) resulted in significant decreases in phase (-61.8%) at theta frequency, peak theta power (-64.2%), and absolute power of the low-frequency theta band (-67%). These electroencephalographic alterations, which appeared at 50.75 nmol AP5, were amplified following application of massive doses of the drug (121.8 nmol, n = 1, and 162 nmol, n = 1). Amplification, however, was slight and the theta waves remained clearly detectable. On the other hand, the infusion of NMDA resulted in a significant increase in frequency (+25%) of this rhythm, but this effect was completely antagonized by prior local administration of 16 nmol AP5. Our data suggest that the septal NMDA receptors exert subtle modulatory influences on the septohippocampal cells involved in physostigmine-induced theta wave production, which has not been reported elsewhere: tonic with respect to both low-frequency theta band power and theta phase, and phasic with respect to theta frequency. Our data also indicate that the septum may be a sensitive action site for exogenously administered glutamatergic drugs.

2-Amino-5-phosphonovalerate↗
PubMed1979

Activities of four glycolytic enzymes (HK, PFK, PK, and LDH) and isozymic pattern of LDH in mouse lung tumor induced by urethan.

In the lungs of CFLP mice the activities of glycolytic key enzymes (HK, PFK, PK) and LDH as well as LDH isozymic pattern change in the course of life. The activities of these glycolytic enzymes in the lung tumors induced by urethan in CFLP mice are significantly higher than those in the normal adult lung and they are similar to those in the normal fetal lung. The isozymic pattern of LDH of pulmonary adenomas resembles that of the normal fetal lung, too.

Age Factors↗
PubMed1976

Diaplacental carcinogenesis: initiation with the carcinogens dimethylbenzanthracene (DMBA) and urethane during fetal life and postnatal promotion with the phorbol ester TPA in a modified 2-stage Berenblum/Mottram experiment.

Diaplacental initiation with the carcinogens DMBA or urethane followed by topical treatment of mice of F-1 generation with the tumor promotor TPA led to the formation of benign and malignant tumors on the back skin and also in various internal organs. (This system constitutes a modified 2-stage experiment based on the early schemes of Berenblum and Mottram.) Application of either the carcinogens or the tumor promoter alone did not lead to the formation of tumors within one year. The highest skin papilloma yield was obtained with mice initiated with DMBA from the 16--19th day of fetal life. The highest total tumor yield was obtained after initiation from day 18--21st. The combination urethane/TPA also promoted the formation of tumors of the skin and other organs. The significance of this modified prenatal-postnatal initiation/promotion scheme in human pathology is discussed.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Cardiovascular-compensatory and decompensatory responses in rats anesthetized with pentobarbital compared to chloralose-urethane.

The data presented in these studies suggests that rats anesthetized with pentobarbital are better able to compensate for acute blood loss, but are less able to sustain the compensatory effort during hemorrhagic hypotension than rats anesthetized with chloralose-urethane. However, following reinfusion of shed blood the pentobarbital rats are better able to maintain their blood pressure.

Anesthesia↗
PubMedDate not supplied

Implantable enzyme capsules for cancer chemotherapy from bakers' yeast cytosine deaminase immobilized on epoxy-acrylic resin and urethane prepolymer.

For trial use in the local chemotherapy of cancer by a combination of cytosine deaminase (EC 3.5.4.1) and 5-fluorocytosine (J. Biotechnol., (1985), 2, 13-21), 40 U of partially purified cytosine deaminase was obtained from 500 g of commercial compressed bakers' yeast. The enzyme, which is unstable, was immobilized to stabilize it by the use of commercial epoxy-acrylic beads (Eupergit C). The immobilized enzyme was made into enzyme capsules with cellulose tubing for dialysis to encapsulate it or urethane polymer to entrap it, which materials are biocompatible. The activity of the intact cellulose capsules thus made was 0.4% that of the immobilized enzyme inside. The enzyme capsules also were stable. Ten days after the cellulose capsules were implanted in rats, 25% of the starting activity remained. When the polyurethane capsules were tested in vitro for 9 mo for thermostability at 37 degrees C, the activity decreased rapidly (with a half-life of 28 d) during the first 4 mo, and then slowly (half-life, about 100 d) during the next 5 mo. A calculation to transform the biphasic decline into a sum of the exponential decline of two components of enzymic activities with different strengths and half-lives showed that the larger half-life was 5 mo.

Antineoplastic Agents↗
PubMed2003

Hypotensive effect of anandamide through the activation of CB1 and VR1 spinal receptors in urethane-anesthetized rats.

This study examined the effect of intrathecal (i.t.) injection of the endocannabinoid anandamide in urethane-anesthetized rats. The tip of the i.t. cannula was positioned at the T(12)-L(1) level of the spinal cord. Either anandamide or its metabolically stable analogue methanandamide (25 to 100 nmol) produced dose-dependent decreases in the blood pressure that persisted at least for up to 30 min. The hypotensive responses to 100 nmol anandamide and to 100 nmol methanandamide were -17.7+/-1.6 mmHg ( n=5) and -17.9+/-2.0 mmHg ( n=4), respectively. Hypotensive effects were also obtained with the CB(1) cannabinoid receptor agonist WIN 55212-2 (20 nmol; i.t.) as well as with the vanilloid VR(1) receptor agonist capsaicin (3 nmol; i.t.). Nicotinic ganglionic blockade with hexamethonium bromide [10 mg/kg; intravenous(i.v.)] abolished the responses to both anandamide and capsaicin. The i.t. administration of the CB(1) receptor antagonist, 20 nmol SR 141716A, as well as the VR(1) receptor antagonist, 20 nmol capsazepine, prevented almost completely the hypotensive responses to both anandamide and methanandamide. SR 141716A prevented the hypotension caused by WIN 55212-2 but did not modify the response to the vanilloid receptor agonist capsaicin. On the contrary, capsazepine antagonized the hypotension caused by capsaicin but failed to affect the decrease in blood pressure caused by the CB1 cannabinoid receptor agonist WIN 55212-2. These results suggest that anandamide could modulate the blood pressure through the activation of cannabinoid CB(1) receptors and vanilloid VR(1) receptors localized at the spinal cord.

Anesthesia, Intravenous↗
PubMed1984

Differences in thermal responses of cat trigeminal ganglion 'cold' receptors under urethane and pentobarbital anesthetization.

Cutaneous thermoreceptors recorded from the trigeminal ganglion of cats anesthetized with urethane showed a significant reduction in thermal sensitivity when compared with neuronal responses obtained from sodium pentobarbital-anesthetized cats. The results of this study indicate that a detailed analysis of primary afferent thermoreceptor response characteristics should consider the anesthesia employed.

Anesthesia, General↗
PubMed1986

Discriminative conditioning-related slow potential and single-unit responses in the frontal cortex of urethane-anesthetized rats.

A model is described for obtaining long-term and stable discriminative conditioning-related slow-potential and single-unit responses from the frontal cortex of urethane-anesthetized rats. Responses were recorded and analyzed to reinforced (rewarding medial forebrain bundle stimulation) and non-reinforced tone cues. In the present study, cortical event-related slow potentials provided an adequate index of the level of discriminative conditioning. Single-unit response patterns are described for 57 neurons which demonstrated a discriminative response to either the reinforced or non-reinforced tone cue.

Anesthesia, General↗
PubMed1986

Somatovesical and vesicovesical excitatory reflexes in urethane-anaesthetized rats.

The effect of spinal cord transection on excitatory somato- and vesicovesical micturition reflexes have been investigated in urethane-anaesthetized rats. In adult rats, 3 distinct types of excitatory reflexes to the bladder may be observed: a somatovesical reflex organized at spinal level and two vesicovesical reflexes organized at spinal and supraspinal level, respectively. In agreement with results of lesion experiments (Neurosci. Lett., 8 (1978) 27-33), bladder voiding is abolished following spinal cord transection although both somato- and vesicovesical reflexes may be demonstrated in acute spinal rats. Occurrence of the spinal vesicovesical reflex during the collecting phase of the cystometrogram appears to be inhibited by a supraspinal inhibitory pathway.

Anesthesia↗
PubMed1990

Contrasting effects of urethane and pentobarbitone anaesthesia on the electrical properties of rat jaw-elevator motoneurones.

Our main finding is that elevator motoneurones do not show sustained firing to intracellular injections of depolarising current pulses in rats anaesthetised with urethane. In contrast, virtually all elevator motoneurones show sustained firing in pentobarbitone-anaesthetised rats. The differences in firing are not associated with significant differences in membrane potential, spike amplitudes, AHP amplitude or duration, input resistance, time constant or rheobase (P greater than 0.06 in all cases). However, there are clear differences in the extent of sag seen under the two anaesthetics and so we tentatively suggest that the anaesthetics may differ in their effects on the inward rectifier.

Anesthesia↗