scholarly journals The fate of sulphadimethoxine in primates compared with other species

1970 ◽  
Vol 118 (1) ◽  
pp. 41-45 ◽  
Author(s):  
R. H. Adamson ◽  
J. W. Bridges ◽  
M. R. Kibby ◽  
S. R. Walker ◽  
R. T. Williams

1. The metabolism of sulphadimethoxine (2,4-dimethoxy-6-sulphanilamidopyrimidine) was examined in nine species of primates and nine species of non-primates. 2. The main metabolite of the drug in the urine in man, rhesus monkey, baboon, squirrel monkey, capuchin, bushbaby, slow loris and tree shrew was sulphadimethoxine N1-glucuronide. In the green monkey, although the main metabolite was N4-acetylsulphadimethoxine, the N1-glucuronide was also a major metabolite. 3. In the dog, rat, mouse, guinea pig, Indian fruit bat and hen the N1-glucuronide was a minor metabolite in the urine, whereas in the cat, ferret and rabbit this glucuronide was not found in the urine. 4. All the species examined except the dog excreted some N4-acetylsulphadimethoxine, which was the major metabolite in the green monkey, rabbit and guinea pig. 5. In the tree shrew, a doubtful primate, N1-glucuronide formation was similar to that in the other primates. 6. It is suggested that the slow excretion of the drug by the rat may be due partly to strong binding of the drug to tissue proteins and that the strength of binding may vary with species. 7. In the rat the amount of N1-glucuronide found in the urine is not a true indication of the extent of this conjugation since much more of the conjugate was found in the bile (7% of the dose) than in the urine (1%). In the rabbit, no N1-glucuronide was found in the bile or urine, but a small amount of sulphadimethoxine N4-glucuronide was found in the bile of the rat (0.5% of dose) and rabbit (0.8%).

1970 ◽  
Vol 118 (1) ◽  
pp. 47-51 ◽  
Author(s):  
J. W. Bridges ◽  
M. R. French ◽  
R. L. Smith ◽  
R. T. Williams

1. The urinary excretion of orally administered [14C]benzoic acid in man and 20 other species of animal was examined. 2. At a dose of 50mg/kg, benzoic acid was excreted by the rodents (rat, mouse, guinea pig, golden hamster, steppe lemming and gerbil), the rabbit, the cat and the capuchin monkey almost entirely as hippuric acid (95–100% of 24h excretion). 3. In man at a dose of 1mg/kg and the rhesus monkey at 20mg/kg benzoic acid was excreted entirely as hippuric acid. 4. At 50mg/kg benzoic acid was excreted as hippuric acid to the extent of about 80% of the 24h excretion in the squirrel monkey, pig, dog, ferret, hedgehog and pigeon, the other 20% being found as benzoyl glucuronide and benzoic acid, the latter possibly arising by decomposition of the former. 5. On increasing the dose of benzoic acid to 200mg/kg in the ferret, the proportion of benzoyl glucuronide excreted increased and that of hippuric acid decreased. This did not occur in the rabbit, which excreted 200mg/kg almost entirely as hippuric acid. It appears that the hedgehog and ferret are like the dog in respect to their metabolism of benzoic acid. 6. The Indian fruit bat produced only traces of hippuric acid and possibly has a defect in the glycine conjugation of benzoic acid. The main metabolite in this animal (dose 50mg/kg) was benzoyl glucuronide. 7. The chicken, side-necked turtle and gecko converted benzoic acid mainly into ornithuric acid, but all three species also excreted smaller amounts of hippuric acid.


1975 ◽  
Vol 148 (2) ◽  
pp. 219-225 ◽  
Author(s):  
I Merits

The metabolic fate of [1-14-C]hexadecylsulphate and hexadecyl[35-S]sulphate, administered intravenously as the sodium and trimethylammonium salt to dogs and orally as the erythromycin salt to dogs, rats and humans, was studied. Studies with rats indicated that the compounds were well absorbed and rapidly excreted in the urine. However, after oral administration of the 14-C-and 35-S-labelled hexadecyl sulphate erythromycin salt to dogs, considerable amounts of radioactivity were excreted in the faeces as unmetabolized hexadecyl sulphate. Studies with two humans showed that orally administered erythromycin salt of [1-14C]hexadecyl sulphate was well absorbed in one person but poorly absorbed in the other. Radioactive metabolites in urine were separated by t.l.c. in two solvent systems. The main metabolite of hexadecyl sulphate in the dog, rat and human was identified as the sulphate ester of 4-hydroxybutyric acid. In addition, psi-[14-C]butyrolactone as a minor metabolic product of [1-14-C]hexadecyl sulphate was also isolated from the urine of rat, dog and man. However, there was still another metabolite in dog urine, which comprised about 20% of the total urinary radioactivity and carried both 14-C and 35-S labels. This metabolite was absent from rat urine. The metabolite in dog urine was isolated and subsequently identified by t.l.c. and g.l.c. and by isotope-dilution experiments as the sulphate ester of glycollic acid. Small amounts (about 5% of the total recovered radioactivity in excreta) of labelled glycollic acid sulphate were also found in human urine after ingestion of erythromycin [1-14-C]hexadecyl sulphate.


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.


1969 ◽  
Vol 21 (03) ◽  
pp. 594-603 ◽  
Author(s):  
Y Takada ◽  
A Takada ◽  
J. L Ambrus

SummarySephadex gel filtration of human plasma gave results suggesting the presence of two proactivators of plasminogen, termed proactivators A and B.Activity resembling that of proactivator A was found in rabbit plasma, but not in guinea pig plasma.Plasminogen activators produced by the interaction of proactivator A of human plasma with streptokinase had no caseinolytic or TAMe esterolytic effect.Proactivator A can be separated in a form apparently free from plasminogen, as shown by the heated fibrin plate test and by immunological analysis. On the other hand, proactivator B concentrates prepared so far are contamined with plasminogen.Human proactivators appear to be far more susceptible to streptokinase than are rabbit proactivators.Inhibitors of the fibrinolysin system were observed in the plasmas of all 3 species. These inhibitors are not present in the euglobulin fraction of plasma. Sephadex fractionation of euglobulin fractions results in proactivator preparations that do not contain inhibitors.


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.


SIMULATION ◽  
1968 ◽  
Vol 10 (5) ◽  
pp. 221-223 ◽  
Author(s):  
A.S. Chai

It is possible to replace k2 in a 4th-order Runge-Kutta for mula (also Nth-order 3 ≤ N ≤ 5) by a linear combination of k1 and the ki's in the last step, using the same procedure for computing the other ki's and y as in the standard R-K method. The advantages of the new method are: It re quires one less derivative evaluation, provides an error estimate at each step, gives more accurate results, and needs a minor change to switch to the RK to obtain the starting values. Experimental results are shown in verification of the for mula.


1880 ◽  
Vol 29 (1) ◽  
pp. 47-54
Author(s):  
Thomas Muir
Keyword(s):  

The rows of a determinant of the nth order having been separated into two sets, one containing the first p rows and the other the rest, if each minor of the pth degree formed from the first set be multiplied by a minor, called its complementary, formed from the second set, and the result have its sign chosen in accordance with a certain law, it is well known as an elementary theorem that the aggregate of the products thus obtained is equal to the original determinant.


POETICA ◽  
2021 ◽  
Vol 52 (3-4) ◽  
pp. 228-265
Author(s):  
Rafael Simian

Abstract Guigo II is commonly known and praised among specialists of Western mysticism for his Scala claustralium, a work that presents a spiritual program for cloistered monks. His Meditations, on the other hand, have usually been relegated to the margin of attention. The First Meditation, in particular, is generally regarded as a minor piece. The paper argues, however, that a new approach can make better sense of the First Meditation, while also enabling us to recognize its specific function and value. Seen from this new perspective, Guigo’s purpose with the text is to train and exercise his readers’ minds according to the spiritual program laid out in the Scala. The paper shows that the First Meditation realizes that goal, surprisingly, by having the same essential features that Umberto Eco found in the ‘open works’ of the Western avant-garde.


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.


Development ◽  
1980 ◽  
Vol 60 (1) ◽  
pp. 405-418
Author(s):  
E. B. Ilgren

The growth of mouse trophectoderm depends upon the presence of the inner cell mass. Whether this applies to other species of mammals is not known. To investigate this problem, the guinea pig was selected for two reasons. Firstly, the growth of guinea-pig trophoblast resembles that of man. Secondly, earlier studies suggest that the proliferation of guinea-pig trophectoderm may not be under ICM control. Therefore, in the present study, the guinea-pig blastocyst was cut microsurgically to yield two tissue fragments. These contained roughly equal numbers of trophectodermal cells, one fragment being composed only of trophectoderm and the other containing ICM tissue as well. Subsequently, the growth of these mural and polar fragments was followed in vitro since numerous technical difficulties make an in vivo analysis of this problem impracticable. In a manner similar to the mouse, the isolated mural trophectoderm of the guinea pig stopped dividing and became giant. In contrast, guinea-pig polar fragments formed egg-cylinder-like structures. The latter contained regions structurally similar to two presumptive polar trophectodermal derivatives namely the ectoplacental and extraembryonic ectodermal tissues. These findings suggest that guinea-pig trophectodermal growth may occur in a manner similar to the mouse and thus be under ICM control.


Sign in / Sign up

Export Citation Format

Share Document