scholarly journals The metabolites of cyclohexylamine in man and certain animals

1972 ◽  
Vol 129 (4) ◽  
pp. 857-867 ◽  
Author(s):  
A. G. Renwick ◽  
R. T. Williams

1. [1-14C]Cyclohexylamine hydrochloride was synthesized and given orally or intraperitoneally to rats, rabbits and guinea pigs (dose 50–500mg/kg) and orally to humans (dose 25 or 200mg/person). The 14C is excreted mainly in the urine, most of the excretion occurring in the first day after dosing. Only small amounts (1–7%) are found in the faeces. 2. In the rat, guinea pig and man, the amine is largely excreted unchanged, only 4–5% of the dose being metabolized in 24h in the rat and guinea pig and 1–2% in man. In the rabbit about two-thirds of the dose is excreted unchanged and about 30% is metabolized. 3. In the rat, five minor metabolites were found, namely cyclohexanol (0.05%), trans-3- (2.2%), cis-4- (1.7%), trans-4- (0.5%) and cis-3-aminocyclohexanol (0.1% of the dose in 24h). 4. In the rabbit, eight metabolites were identified, namely cyclohexanol (9.3%), trans-cyclohexane-1,2-diol (4.7%), cyclohexanone (0.2%), cyclohexylhydroxylamine (0.2%) and trans-3- (11.3%), cis-3- (0.6%), trans-4- (0.4%) and cis-4-aminocyclohexanol (0.2%). 5. In the guinea pig, six minor metabolites were found, namely cyclohexanol (0.5%), trans-cyclohexane-1,2-diol (2.5%) and trans-3- (1.2%), cis-3- (0.2%), trans-4- (0.2%) and cis-4-aminocyclohexanol (0.2%). 6. In man only two metabolites were definitely identified, namely cyclohexanol (0.2%) and trans-cyclohexane-1,2-diol (1.4% of the dose), but man had been given a smaller dose (3mg/kg) than the other species (50mg/kg). 7. The hydroxylated metabolites of cyclohexylamine were excreted in the urine in both free and conjugated forms. 8. Although cyclohexylamine is metabolized to only a minor extent, in rats the metabolism was mainly through hydroxylation of the cyclohexane ring, in man by deamination and in guinea pigs and rabbits by ring hydroxylation and deamination.

1940 ◽  
Vol 72 (4) ◽  
pp. 389-405 ◽  
Author(s):  
J. E. Smadel ◽  
M. J. Wall

Anti-soluble substance antibodies and neutralizing substances, which develop following infection with the virus of lymphocytic choriomeningitis, appear to be separate entities. The times of appearance and regression of the two antibodies are different in both man and the guinea pig; the antisoluble substance antibodies appear earlier and remain a shorter time. Moreover, mice develop them but no demonstrable neutralizing substances. Injection of formalin-treated, virus-free extracts containing considerable amounts of soluble antigen fails to elicit anti-soluble substance antibodies and to induce immunity in normal guinea pigs; administration of such preparations to immune pigs, however, is followed by a marked increase in the titer of anti-soluble substance antibodies in their serum. On the other hand, suspensions of formolized washed virus are effective in normal guinea pigs in stimulating both anti-soluble substance antibodies and protective substances, and in inducing immunity to infection.


1927 ◽  
Vol 4 (3) ◽  
pp. 227-244
Author(s):  
ALEXANDER LIPSCHUTZ

An abnormal condition of the external genital organs in 16 otherwise normal female guinea-pigs is described. They possessed an hypertrophied penis-like clitoris and horny styles similar to those in the intromittent sac of the normal male penis. The abnormalities are often asymmetrical, the clitoris and the horny style on one side being more developed than on the other. They may even be absent on one side. It is suggested that the malformation is a peculiar type of "partial somatic intersexuality," the external genital organs resembling those in the male guinea-pig. The condition is identical with that described in the castrated female guinea-pig experimentally masculinised by testicular transplantation. There was no indication of the ovaries producing simultaneously female and male sexual hormones: (a) The ovaries were histologically normal. (b) The ovaries when engrafted into castrated males produced the typical female hormonic effect on the mammary glands and had no influence on the penis or on the horny styles. (c) The clitoris and the horny styles of the intersexual females were not affected by removal of the ovaries, whereas in the male removal of the testes caused a pronounced regression of the horny styles even in fully grown animals. (d) The horny styles when cut regenerated even after removal of the ovaries; there is never a regeneration in the castrated male, but only in the normal male. The question is discussed whether the described type of intersexuality might be a case of "successive hormonic intersexuality," both kinds of sexual hormones having been produced simultaneously for a certain time whereas at a later stage only female hormones were secreted. The hypertrophied clitoris and the horny styles would then be considered as "fixed" sex characters persisting after the disappearance of the male sexual hormones. The problem of fixation of sex characters by sexual hormones is considered on experimental lines. The facts observed are rather against the suggestion that the intersexuality described is a case of successive hormonic intersexuality. Other possibilities of explaining the morphogenetic basis of this peculiar type of intersexuality are also discussed. The intersexuality described is of an hereditary nature.


1976 ◽  
Vol 230 (5) ◽  
pp. 1400-1405 ◽  
Author(s):  
PS Kulkarni ◽  
AR Wakade ◽  
SM Kirpekar

The relative contribution of the ovarian nerves and hypogastric plexus in the innervation of the guinea pig uterus and ovary was assessed. Chronic section of the hypogastric nerve did not reduce norepinephrine (NE) concentration in either organ. Localization of the hypogastric plexus in female guinea pigs was unsuccessful. Crushing the ovarian nerves 1) lowered the NE concentration in the ovary (70%) and in all portions of the uterus (86%), 2) decreased by 80-90% the uterine retention of [3H]NE, and 3) decreased the intensity of fluorescent adrenergic fibers in the uterus. However, the denervated uterus failed to exhibit supersensitivity to NE. In conclusion, sympathetic innervation of the guinea pig uterus and ovary is predominantly via the ovarian nerves, and a minor pathway of innervation may come from hypogastric plexus.


1974 ◽  
Vol 138 (3) ◽  
pp. 445-451 ◽  
Author(s):  
Abdulla A.-B. Badawy ◽  
Myrddin Evans

1. When assayed in fresh homogenates, guinea-pig liver tryptophan pyrrolase exists only as holoenzyme. It does not respond to agents that activate or inhibit the rat liver enzyme in vitro. Only by aging (for 30min at 5°C) does the guinea-pig enzyme develop a requirement for ascorbate. 2. The guinea-pig liver enzyme is activated by the administration of tryptophan but not cortisol, salicylate, ethanol or 5-aminolaevulinate. 3. The tryptophan enhancement of the guinea-pig liver pyrrolase activity is prevented by 0, 34 and 86% by pretreatment with actinomycin D, cycloheximide or allopurinol respectively. 4. The guinea-pig liver tryptophan pyrrolase is more sensitive to tryptophan administration than is the rat enzyme. On the other hand, the concentrations of tryptophan in sera and livers of guinea pigs are 45–52% less than those in rats. 5. It is suggested that tryptophan may regulate the activity of guinea-pig liver tryptophan pyrrolase by mobilizing a latent form of the enzyme whose primary function is the detoxication of its substrate.


1921 ◽  
Vol 33 (2) ◽  
pp. 231-238 ◽  
Author(s):  
Charles C. Lund ◽  
Louis A. Shaw ◽  
Cecil K. Drinker

The distribution of manganese dioxide particles 1 hour following intravenous injection in cats, dogs, rabbits, guinea pigs, rats, chickens, and turtles is described. This distribution is remarkably constant for all the animals tested, except the cat, in which the injected material is practically equally divided between the lungs and liver. In the other animals the liver performs the main share of the work, and in the cat it has been shown that the liver after 12 hours accumulates the manganese which was formerly deposited in the lungs. The results are in harmony with experiments in which bacterial suspensions are employed for injection and confirm the suggestion previously made (2) that in the first handling of foreign particulate material the animal behaves similarly whether protein or inorganic injections are used.


1934 ◽  
Vol 30 (2) ◽  
pp. 224-227

The All-Ukrainian Bacteriological Institute is developing with successful results the question of protective vaccinations against typhus. A number of experiments performed on guinea pigs showed that guinea pig infected with typhus passerine virus and having suffered the disease is immune to subsequent infection with the blood of a typhus-typhoid patient. On the other hand, guinea pig infected with the blood of a typhoid patient and having survived the disease appears immune to infection with the guinea pig passage virus.


2005 ◽  
Vol 71 (12) ◽  
pp. 7927-7932 ◽  
Author(s):  
Stig Rønhede ◽  
Bo Jensen ◽  
Søren Rosendahl ◽  
Birthe B. Kragelund ◽  
René K. Juhler ◽  
...  

ABSTRACT Several asco-, basidio-, and zygomycetes isolated from an agricultural field were shown to be able to hydroxylate the phenylurea herbicide isoproturon [N-(4-isopropylphenyl)-N′,N′-dimethylurea] to N-(4-(2-hydroxy-1-methylethyl)phenyl)-N′,N′-dimethylurea and N-(4-(1-hydroxy-1-methylethyl)phenyl)-N′,N′-dimethylurea. Bacterial metabolism of isoproturon has previously been shown to proceed by an initial demethylation to N-(4-isopropylphenyl)-N′-methylurea. In soils, however, hydroxylated metabolites have also been detected. In this study we identified fungi as organisms that potentially play a major role in the formation of these hydroxylated metabolites in soils treated with isoproturon. Isolates of Mortierella sp. strain Gr4, Phoma cf. eupyrena Gr61, and Alternaria sp. strain Gr174 hydroxylated isoproturon at the first position of the isopropyl side chain, yielding N-(4-(2-hydroxy-1-methylethyl)phenyl)-N′,N′-dimethylurea, while Mucor sp. strain Gr22 hydroxylated the molecule at the second position, yielding N-(4-(1-hydroxy-1-methylethyl)phenyl)-N′,N′-dimethylurea. Hydroxylation was the dominant mode of isoproturon transformation in these fungi, although some cultures also produced traces of the N-demethylated metabolite N-(4-isopropylphenyl)-N′-methylurea. A basidiomycete isolate produced a mixture of the two hydroxylated and N-demethylated metabolites at low concentrations. Clonostachys sp. strain Gr141 and putative Tetracladium sp. strain Gr57 did not hydroxylate isoproturon but N demethylated the compound to a minor extent. Mortierella sp. strain Gr4 also produced N-(4-(2-hydroxy-1-methylethyl)phenyl)-N′-methylurea, which is the product resulting from combined N demethylation and hydroxylation.


1968 ◽  
Vol 5 (2) ◽  
pp. 97-101 ◽  
Author(s):  
Robert F. McConnell ◽  
Raymond D. Ediger

Thirty-six hundred ninety-eight guinea pigs of the Dunkin-Hartley strain from the breeding colony at Fort Detrick were necropsied. Four females had mesenchymomas of the heart. The tumors were similar histologically and were composed of multiple benign mesenchymal tissues which were amalgamated into a single mass. One tumor was composed of fibrous, angiomatous, adipose, cartilagenous, osscous, hematopoietic, myxomatous, and possibly smooth muscle tissues. Smooth muscle and myxomatous tissues were not found in the other tumors. All were benign and probably originated from the primitive mesenchyme of the heart.


1980 ◽  
Vol 85 (3) ◽  
pp. 429-434 ◽  
Author(s):  
C. SUMIDA ◽  
C. GELLY ◽  
J. R. PASQUALINI

The responsiveness of the uterus of the guinea-pig to oestrogen treatment was studied in the fetal and perinatal periods. Twenty-four hours after one dose of 1 mg oestradiol/kg body wt to the pregnant guinea-pig, there was no significant increase in uterine wet weight of the fetus but a sevenfold increase in the concentration of progesterone receptors. In the perinatal period, doses of 1,10 and 100 μg oestradiol led to as much as an 80% increase in uterine wet weight after 24 h in both 2- and 7-day-old guinea-pigs. On the other hand, levels of progesterone receptors in newborn animals showed a smaller increase (twofold) than that which occurred in the fetal uterus. In both fetal and newborn guinea-pigs, total oestradiol-receptor concentrations (both available and occupied binding sites) decreased significantly after treatment with oestradiol. It was concluded that the hormonal effect of oestradiol on progesterone-receptor synthesis can be expressed in the fetus and to an even greater extent than in the perinatal period over the same period of time. In the fetus, this response can be distinguished from the overall uterotrophic effect of oestradiol.


1920 ◽  
Vol 31 (6) ◽  
pp. 765-784 ◽  
Author(s):  
Leo Loeb

1. After transplantation of the thyroid of the guinea pig into rats there is a primary injury of the transplant, noticeable as early as 3, 4, and 5 days after transplantation. The tissue is less resistant, and it is preserved only under the best conditions. The number of mitoses is much diminished in the transplant, but they may appear even as late as 9 days after transplantation. This was also the latest time at which living tissue was found. Epithelium is best preserved in the neighborhood of growing fibroblastic tissue, and growing epithelium attracts fibroblasts. Few fibroblasts grow between acini, and they have a tendency to form fibrous tissue. Dense fibrous tissue compresses acini and contributes to their destruction. The vascularization of the graft is very poor, but some capillaries may penetrate between acini. The collection of lymphocytes around acini is only casual and may be found where fibroblasts are active and especially around the blood vessels in the capsule of the graft. On the whole, heterotransplanted tissue does not attract lymphocytes to any marked extent. Connective tissue and lymphocytes contribute only secondarily and to a minor extent to the destruction of the heterotransplant. 2. After transplantation of the thyroid of the rabbit into rats the last mitoses are found 9 days after transplantation; living acini are observed as late as 11 days after transplantation, and ducts of squamous epithelium even somewhat later. Different kinds of tissue seem to show a different degree of resistance to the action of heterotoxins. The difference in the resistance to heterotoxins corresponds to the difference in the resistance of various tissues to other kinds of injurious influences. The thyroid of rabbits is, on the whole, better preserved in the rat than the thyroid of the guinea pig; there is also more mitotic activity in the rabbit thyroid. The reaction of the tissues of the host towards heterotransplanted rabbit thyroid in principle is similar to the reaction to heterotransplanted guinea pig thyroid. 3. After transplantation of rabbit thyroid into guinea pigs well preserved thyroid is found not later than 8 days, while the last mitoses appear 6 days after transplantation. The number of mitoses is very small. The host tissues again behave in a manner characteristic of heterotransplantation. It is probable that slight infections and the presence of polynuclear leucocytes are responsible for the somewhat inferior results in this kind of heterotransplantation. 4. After transplantation of cat thyroidinto the rat, signs of degeneration in the transplanted acini appear at the end of the 1st week; they increase during the 2nd week. The last well preserved acini are found at 14 days; a few degenerating acini are still visible as late as 18 days after transplantation. Almost all pieces are entirely necrotic in the 3rd week. Mitoses are only found 5, 9, 10, and 11 days after transplantation, and they are present in a limited number. There is a decided lack of good vascularization in the transplants; it is especially noticeable in the 2nd week after transplantation. Fibroblasts penetrate at various places between the acini and occasionally together with a few lymphocytes may destroy some of them. From the 9th day on the presence of fibrous tissue around the acini is noticeable. It compresses the acini and thus contributes to their destruction. Even the heterotransplanted thyroid exhibits a restraining influence on the connective tissue which is greater than that presented by dead material. The behavior of the lymphocytes towards heterotransplanted thyroid of the cat is similar to that towards other heterotransplanted thyroid.


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