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Showing papers by "Laval University published in 1977"


Journal ArticleDOI
Georges Pelletier1, R. Leclerc1, Fernand Labrie1, J. Cote1, M Chretien1, M. Lis1 
TL;DR: Results suggest that β-LPH is stored in the same secretory granules as ACTH and that both hormones are released together during granule extrusion.
Abstract: Identification of the β-lipotropic hormone (β-LPH)-producing cells in several species, including man, was performed with the technique involving use of the unlabeled antibody and peroxidase- antiperoxidase complex. Serial paraffin and ultrathin sections were treated for detection of both β-LPH and ACTH at the light and electron microscopic levels. It was clearly shown that β-LPH could be found only in the corticotropic cells located in the pars intermedia and pars distalis of all species studied. At the electron microscope level, it could be established that β-LPH is contained in all the secretory granules of positive cells. These results suggest that β-LPH is stored in the same secretory granules as ACTH and that both hormones are released together during granule extrusion. (Endocrinology 100: 770, 1977)

207 citations


Journal ArticleDOI
TL;DR: More than an elevation of endogenous LH, whether induced by single or repeated injection of a potent LHRH agonist, is capable of down regulating testicular LH receptors with a resultant long-term effect of reduced testicular size and decreased plasma testosterone concentration.

179 citations


Journal ArticleDOI
C. Auclair1, Paul A. Kelly1, D. H. Coy1, Andrew V Schally1, Fernand Labrie1 
TL;DR: Data indicate that a LHRH agonist, when given at a relatively low dose, is capable of reducing testicular LH/hCG and PRL receptor levels as well as testicular function, the effect being probably mediated by increased endogenous gonadotropin secretion.
Abstract: Injection of male rats with 40-200 ng of [D-Leu6, des-Gly-NH2(10)]LHRH ethylamide for 7 days caused a maximal 80% reduction of testicular LH/hCG receptor level with one injection per day being as efficient as 3 daily injections. A similar inhibitory effect was observed on testicular PRL receptors. Testis and seminal vesicle weight as well as plasma testosterone levels were also significantly reduced by this treatment. These data indicate that a LHRH agonist, when given at a relatively low dose, is capable of reducing testicular LH/hCG and PRL receptor levels as well as testicular function, the effect being probably mediated by increased endogenous gonadotropin secretion.

144 citations


Journal ArticleDOI
TL;DR: It was observed that prolactin receptors remain at a relatively low and constant level while mammary development (mammogenesis) takes place, and there is an almost linear increase in the weight of the mammary gland from Day 14 of pregnancy until Day 6 of lactation and this increase is unaffected by CB 154 treatment.
Abstract: The numbers and affinity of prolactin receptors in the rabbit mammary gland were determined during pregnancy and early lactation under conditions in which the endogenous lactogenic hormone was depleted by means of the compound CB 154. In untreated rabbits the number of prolactin binding sites per mg protein increased from 25 ± 3 (SE) fmol at Day 14 of gestation to 54.8 ± 5.8 fmol/mg at Day 22, after which binding declined to 14.2 ± 8.5 fmol/mg, then increased in late pregnancy and during lactation to 110.5 ±11.5 fmol/mg at Day 28. In animals treated with CB 154, binding was always higher than in non-treated animals, with a peak during pregnancy of 149 ± 24 fmol/mg at Day 22. After declining in late pregnancy, the number of receptors was highest at Day 6 of lactation (257.4 ± 34.6 fmol/mg). There is an almost linear increase in the weight of the mammary gland from Day 14 of pregnancy until Day 6 of lactation and this increase is unaffected (except at Day 6 of lactation) by CB 154 treatment. It was observed...

139 citations


Journal ArticleDOI
TL;DR: It is shown that β-endorphin and met-enkephalin have a more potent and more rapid stimulatory effect on PRL than GH release after intracerebral injection, suggesting a possible role of endogenous opiate-like peptides in the control of both PRL and GH secretion.

136 citations


Journal ArticleDOI
TL;DR: It is shown that the first step in the breakdown of met-enkephalin in both plasma and brain tissue is cleavage of the Tyr-Gly amide bond, which offers an explanation for the low activity of meet-enkphalin after intraventricular or intravenous administration.

115 citations


Journal ArticleDOI
M.D. High1, B. Čujec1
TL;DR: In this article, the 12C + 12C fusion cross section has been studied over the energy range 2.46 ≦ Ec.m. ≦ 5.88 MeV.

104 citations


Journal ArticleDOI
TL;DR: The data indicate that the hypothalamic regulatory mechanism for pituitary GH release develops during the neonatal period of the rat and suggest that GHRIH may play an important physiological role in this process.
Abstract: Using a specific radioimmunoassay technique for somatostatin (GHRIH), we have studied the ontogenesis of hypothalamic GHRIH in relation to pituitary and serum GH concentrations in immature rats. Hypothalamic GHRIH concentration rose from minimal levels of 4.5 ± 0.2 pg/μg protein (mean ± SEM) at 2 days to peak concentrations of 40.6 ±4.1 pg/μg protein at 28 days followed by a progressive decline toward 50 days (7.0 ± 0.8 pg/μg protein). Pituitary GH concentration attained peak prepuberal values of 203.5 ± 22.8 ng/μg protein at 16 days with a further marked rise after puberty. Serum GH concentration was elevated at 2 days (53.3 ± 5.7 ng/μl) and declined progressively to 5.9 ± 1.5 ng/μl at 13 days. There was a highly significant inverse correlation between hypothalamic GHRIH and serum GH concentrations (r = -0.743, P < 0.005). These data indicate that the hypothalamic regulatory mechanism for pituitary GH release develops during the neonatal period of the rat and suggest that GHRIH may play an important phys...

98 citations


Journal ArticleDOI
11 Aug 1977-Nature
TL;DR: It is shown that the two analogues resistant to enzymatic degradation, Met-enkephalin and D-Ala2, can stimulate prolactin and growth hormone release after intraventricular injection at a level of potency which is 500 to 5,000 times higher than that of the natural Met- enkephaline molecule.
Abstract: MORPHINE stimulates prolactin and growth hormone secretion1,2, so the identification of brain peptides with opiate-like activity (methionine-enkephalin and leucine-enkephalin)3 raised the possibility that these peptides, beside their role as modulators of pain4, could also be involved in the control of neuro-endocrine functions. We did in fact find that Met-enkephalin administered intraventricularly led to a stimulation of prolactin and growth hormone release5–7. β-Endorphin (β-LPH61–91) was, however, found to be 500 to 2,000 times more potent than Met-enkephalin (β-LPH61–65) in stimulating the release of the pituitary hormones. Since both peptides show similar affinity for the opiate receptor when binding studies are performed at 0 °C in conditions of minimal enzymatic degradation8,9, the markedly different biological activities of the two peptides after intracerebral injection are likely to be due to a more rapid inactivation of Met-enkephalin. We show here that the two analogues resistant to enzymatic degradation, [D-Ala2]Met-enkephalin and [D-Ala2]Met-enkephalinamide can stimulate prolactin and growth hormone release after intraventricular injection at a level of potency which is 500 to 5,000 times higher than that of the natural Met-enkephalin molecule.

88 citations


Journal ArticleDOI
TL;DR: Using an immunohistochemical technique at the electron microscopic level, it has been shown that alpha-MSH is localized within the small vesicles of a few cell bodies found in the arcuate nucleus and numerous nerve fibers widely distributed throughout the brain.
Abstract: Using an immunohistochemical technique at the electron microscopic level, it has been shown that alpha-MSH is localized within the small vesicles of a few cell bodies found in the arcuate nucleus and numerous nerve fibers widely distributed throughout the brain. These findings suggest that alpha-MSH could possibly be considered as a neurotransmitter.

78 citations


Journal ArticleDOI
TL;DR: The microbiological oxidation of ferrous iron in batch and continuous systems has been investigated in relation to uranium extraction from a low‐grade ore by Thiobacillus ferrooxidans and results showed that uranium extraction as high as 68% has been realized during nine days of treatment.
Abstract: The microbiological oxidation of ferrous iron in batch and continuous systems has been investigated in relation to uranium extraction from a low-grade ore by Thiobacillus ferrooxidans. The influence of the parameters, agitation, and aeration on oxygen saturation concentration, rate of oxygen mass transfer, and rate of ferrous iron oxidation was demonstrated. The kinetic values, Vmax and K were determined using an adapted Monod equation for different dilution rates and initial concentrations of ferrous iron. The power requirements for initial leaching conditions were also calculated. Uranium extraction as high as 68% has been realized during nine days of treatment. Regrinding the leach residue and its subsequent leaching yielded 87% uranium solubilization.

Journal ArticleDOI
Nicholas Barden1, Michel Lavoie1, André Dupont1, Jean Côté1, J. Cote1 
TL;DR: Addition of anti-somatostatin serum to rat islets of Langerhans resulted in a marked stimulation of glucagon release with no change in the rate of insulin secretion during the entire 90 min period during which the secretion of both hormones was followed.
Abstract: Addition of anti-somatostatin serum to rat islets of Langerhans which had been previously maintained in organ culture for 48h, resulted in a marked stimulation of glucagon release with no change in the rate of insulin secretion during the entire 90 min period during which the secretion of both hormones was followed. Prior saturation of the anti-somatostatin serum with somatostatin prevented the stimulatory action on glucagon release. These data strongly suggest a physiological role for endogenous somatostatin in the control of glucagon secretion.

Journal ArticleDOI
J. Munro1, J. Bédard1
01 Oct 1977-The Auk
TL;DR: The social and ecological conditions that prevail at and shortly after hatching and lead, within a few days, to the fixation of familial bonds and thus to numerically aberrant family units (creches) are sought.
Abstract: -The formation of creches was studied in the Common Eider (Somateria mollissima) nesting at high density on Bicquette Island in the St. Lawrence River estuary. Aspects of social behavior relevant to creche formation are examined in detail. Data from 293 individually tagged females aided in elucidating the breeding history and in understanding the parental behavior of previously recognized categories of adult females ('B-Brooding,' 'A-Associate,' 'V-Visiting,' and 'N-Neutral'). Creches resulting from the encounter between two or more broods begin to form immediately after the nest exodus and last well into the rearing period (about 10 weeks). The encounters themselves may be stimulated by alarm or predation or may sometimes result from the mutual attraction of ducklings. Our figures reveal that the rate of fixation of such encounters into permanent creches decreases from a high of 88% in broods reaching the shore of the nesting island to a low of 0-6% in encounters between groups meeting during the latter half of the rearing period (between the 4th and the 10th weeks). Agonistic interactions among B-status females tending creches provoke a hitherto unexplained lowering of the ratio of females to ducklings in such groups. Instead of a loose system of cooperation between females rearing creches as was previously surmised, we found rather that the organization of these groups is based upon a hierarchical ranking of females involved in tending. The creche is thus seen as an accidentally expanded family. Departement de Biologie, Faculte des Sciences et de Genie, Cite Universitaire, Universite Laval, Quebec, Que., Canada GIK 7P4. Accepted 17 May 1976. A NUMBER of Anatinae display creching behavior (see Gorman and Milne 1972 for a recent review). Creche was defined elsewhere as the grouping of any number of parentally unrelated adult female(s) and young (Munro 1975). In the Common Eider (Somateria mollissima) of the St. Lawrence estuary, amalgamation of broods into creches sometimes resulted from accidental encounters between two or more broods and sometimes represented a spontaneous tendency to regroup in the face of larid predation. In the latter case, the behavior conferred a distinct survival advantage to the young in most cases (Munro 1975). Once formed, a creche was very stable from the time of settling in the coastal rearing areas at about 1 week of age, to fledging, at about 10 weeks of age (Munro 1975). Even a creche consisting of up to 35 ducklings and 2 females behaved as a cohesive family unit. In the present paper, we seek to understand the social and ecological conditions that prevail at and shortly after hatching and lead, within a few days, to the fixation of familial bonds and thus to numerically aberrant family units (creches). To this end, we describe in fairly minute detail various aspects of the behavior of the various categories of birds involved in creching. We also discuss the influence of duckling age on creche formation and the proportion of encounters resulting in permanent amalgamation. STUDY AREA AND METHODS About 20,000 pairs of Common Eiders breed in the St. Lawrence estuary, 92% being found on 6 nesting islands (see Reed 1973 and Munro 1975 for details). A discrete peak of hatching occurs between 10 and 20 June and the majority of broods and/or creches are rapidly led by adult females to mainland littoral areas for the duration of the rearing period. The length of the sea crossings involved varies between 3 and 14 km. Most ducklings are reared along the southern shore of the river between Kamouraska and Matane, with smaller numbers remaining around the largest islands or moving to the northern shore between the Saguenay River and Forestville. Over 1,400 breeding females were marked with patagial tags during 1972 and 1973, and a few entire broods andlor creches were marked as they were leaving nesting islands. The ducklings were marked with 759 The Auk 94: 759-771. October 1977 This content downloaded from 157.55.39.128 on Mon, 18 Jul 2016 06:11:48 UTC All use subject to http://about.jstor.org/terms 760 MUNRO AND J. BtDARD [Auk, Vol. 94 colored nape tags, which did not disrupt brood unity but did cause a significant increase in predation. Therefore, the tagging of broods was discontinued after marking 140 young in 24 different groups. Four discrete categories of female behavior were recognized. (1) Broody (B). Assumes the leadership of the brood/creche. She does all or most of the vocalizations and surveillance and swims in a central or fore position in the group; does not abandon ducklings except under most extreme disturbance. Two, or rarely three, B-status birds may accompany a creche on a permanent basis with little or no aggression between them. (2) Associate (A). Assumes a subordinate role to the B-female. Swims in a peripheral or rear position in a creche. Readily leaves the ducklings in the case of moderate disturbance. Generally associates with the same creche over several consecutive days. (3) Visiting (V). Has a very low and transitory broodiness. Such females are temporarily attracted to a nearby brood or creche. Show ambiguous (care-giving and agonistic) behavior towards ducklings. May swim alongside a creche for variable lengths of time but leave at the slightest disturbance. May visit a number of different creches in the same day. (4) Neutral (N). Displays no broodiness whatsoever and is not attracted by a nearby creche or brood. Some of the V-females may probably assume an N-status at certain times and vice versa. Generally 5 min of continuous observation are sufficient to classify a female. Further explanations of these categories are found in

Journal ArticleDOI
TL;DR: Over a growth period of 100 days, the rate of infection under low light intensities was more rapid and the percentage of infection higher than on mycorrhizal plants cultivated under a light of 15 and 20 klux.
Abstract: SUMMARY Four different light intensities exerted distinctly different effects on the formation, reproduction and influence of vesicular-arbuscular mycorrhiza on onion plants. Over a growth period of 100 days, the rate of infection under low light intensities (5 and 10 klux) was more rapid and the percentage of infection higher than on mycorrhizal plants cultivated under a light of 15 and 20 klux. The production of spores increased with light intensity. A plant growth enhancement occurred at all light levels but was most pronounced under a 10 klux light regime.

Journal ArticleDOI
01 Feb 1977-Steroids
TL;DR: "in vitro" evidences are shown for the existence of a highly active 3alpha-hydroxysteroid dehydrogenase in the crude cytosol of rat muscle homogenates; the use of 5alpha-dihydrotestosterone (DHT) is therefore compromised in receptor binding measurements because of its extensive metabolism.


Journal ArticleDOI
TL;DR: Ternary storage elements are realized using ternary operators and fundamental circuits, designed with the COS/MOS integrated circuits, and a divide-by-M ternARY counter which can be programmed is described.
Abstract: Ternary storage elements are realized using ternary operators and fundamental circuits, designed with the COS/MOS integrated circuits. Several ternary flip-flops (tri-flops) are constructed and described in detail: the PZN (set positive, set zero, and set negative), the clocked PZN, the D-type, and the T-type. Ternary shift registers and ring counter are formed by means of these tri-flops. A master-slave T-type tri-flop is used for the construction of a ternary up counter able to count from 0 to 3n using the normal ternary code or from -(3n-1)/2 to+(3n -1)/2 when the signed-ternary code is employed. With a small modification, a ternary down counter is also constructed. A divide-by-M ternary counter which can be programmed is described. A memory cell is designed for the construction of a ternary random-access-memory array (TRAM). A ternary decoder and encoder are presented to be the elements of a complete ternary read-only memory (TROM). A modified ternary inverter (MTI) is taken as a unit cell of the ternary memory matrix.

Journal ArticleDOI
TL;DR: The following effects were exerted by a short conditioning mesencephalic RF stimulation on cortically evoked events in single LI or LP thalamic neurons: increased probability of the early, antidromically or orthodromically elicited discharges; decreased probability of late discharging; shortened latency of the subsequent inhibitory period; and reduction in the duration of the first inhibitory phase.

Journal ArticleDOI
01 Dec 1977-Cancer
TL;DR: It remains to be seen whether all dysplasias form one continuum or whether there are two morphologically similar but biologically distinct forms of dysplasia: one more frequent, regressing spontaneously, the other relatively rare, progressing to carcinoma in situ and invasive squamous carcinoma of the cervix.
Abstract: Age at first coitus and use of oral contraceptives were studied in a highly homogeneous population (French Canadian) during a cytologic cervical cancer screening program. Both factors were known in 84,540 women without cervical lesions and in 2017 patients with mild and moderate dysplasia. Highly significant correlations were found between: early onset of sexual activity and occurrence of dysplasia; oral contraceptive use and occurrence of dysplasia; early age at first coitus and oral contraceptive use. When correlated for age at first coitus, there was a significant excess of dysplasias in oral contraceptive users. Dysplasia of the uterine cervix behaves epidemiologically like carcinoma in situ and invasive squamous carcinoma, that is, essentially as a venereal disease. It remains to be seen whether all dysplasias form one continuum or whether there are two morphologically similar but biologically distinct forms of dysplasia: one more frequent, regressing spontaneously, the other relatively rare, progressing to carcinoma in situ and invasive squamous carcinoma of the cervix.

Journal ArticleDOI
TL;DR: Three analogs of somatostatin were synthesized by the solid phase method and tested for their effects on the release of insulin, glucagon, and growth hormone, finding that these analogs could possibly be useful for the treatment of diabetes mellitus.

Journal ArticleDOI
TL;DR: The numerous cases of cortically elicited synaptic excitation in LI-LP cells, taken together with evidence of an unexpectedly high proportion of corticothalamic neurons found in parallel experiments of this laboratory, support the suggestion that complex functions of the "association" cortex partially depend on its downstrem connections with thalamic integrative structures.



Journal ArticleDOI
TL;DR: Somatostatin-containing fibers were also detected in the neurovascular zone of the pituitary stalk, suggesting that somatstatin is released in that region to reach the capillaries in the pituitsary portal plexus.
Abstract: In order to identify clearly the nervous structures containing somatostatin in the human hypothalamus, an immunohistochemical localization of this neurohormone was performed at light-microscopic level. Using a antiserum specific to somatostatin and the unlabeled antibody peroxidase-antiperoxidase technique, we have found somatostatin in neurons with cell bodies in an area in the anterior hypothalamus corresponding to the infundibular nucleus. Somatostatin-containing fibers were also detected in the neurovascular zone of the pituitary stalk, suggesting that somatostatin is released in that region to reach the capillaries in the pituitary portal plexus. A large bundle of somatostatin fibers extending from the anterior part of the paraventricular nucleus up to the posterior portion of the mammillary bodies has also been detected. The role of these fibers still remains to be clarified.

Journal ArticleDOI
TL;DR: A technique that allows in vivo measurements of the specific impedance of brain structures is analysed and implemented and uses the 4-electrode method, which includes an optically isolated current source and an interchangeable electrode module.
Abstract: A technique that allowsin vivo measurements of the specific impedance of brain structures is analysed and implemented. This technique uses the 4-electrode method. The system includes an optically isolated current source and an interchangeable electrode module. Tests on the measuring system, including the electrodes and calibration procedures, are presented. Experiments in media of known resistivity and in cat brains define the present limits of the spatial resolution.

Journal ArticleDOI
Claude Gagné1, Pierre Auger1, Sital Moorjani1, D. Brun1, Paul-J. Lupien1 
TL;DR: It is concluded that the triglyceride contained in very-low-density lipoprotein does not affect hemoglobin measurement, while triglyceridecontained in chylomicrons increased hemoglobin readings linearly.
Abstract: The effects of plasma triglyceride levels on the measurement of hemoglobin and other erythrocyte indices have been studied in blood samples from ten healthy controls, 11 patients with type IV hyperlipoproteinemia, and five patients with hyperchylomicronemia (type I or V). Measurements were made using erythrocytes in their own plasmas and repeated after resuspension of the cells in physiologic saline solution. Hemoglobin, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration were decreased by removal of plasma in erythrocytes from three patients with hyperchylomicronemia. It is concluded that the triglyceride contained in very-low-density lipoprotein does not affect hemoglobin measurement, while triglyceride contained in chylomicrons increased hemoglobin readings linearly.

Journal ArticleDOI
TL;DR: A new and easy experimental method to obtain selected high order circular modes, or multiple modes, spatially separated using a TEA CO2 laser in a conical resonator and Casperson's method is reported.
Abstract: was inserted in the beam to force all portions of the wavefront to oscillate in phase. The main advantage of the method is a more efficient use of the stored energy in the laser, and Casperson suggests the possibility of a tenfold increase in the intensity at a distant target. To use Casperson's method, the cavity will have to be forced to oscillate in one selected high order mode. We believe that this method could also be used with a laser beam consisting of a few high order modes, if these are spatially separated and if they have a known fixed phase relationship. In this Letter we report a new and easy experimental method to obtain selected high order circular modes, or multiple modes, spatially separated. This is done using a TEA CO2 laser in a conical resonator. The experimental arrangement of Fig. 1 represents schematically the TEA CO2 laser with an active medium 1 m long and a 5-cm electrode gap. An axicon is used as the total reflector, and the coupler is a standard, partially transmitting mirror. The apex angle a of the axicon, the radius of curvature of the output mirror, the diameter of the aperture, and the length of the resonator cavity can be varied to select the desired oscillation mode. A few resonator modes were selected and are shown in Fig. 2 as photographs of burn patterns. Over twenty different oscillation modes were obtained in a few hours of experiment by simply varying the aperture diameter between 1 cm and 5 cm and the cavity length between 1.2 m and 3 m. Different axicon-output mirror combinations of two axicons (179°55' and 179 ° 50') were used along with three output mirrors (radius = 10 m, 20 m, ∞). Figure 2(A) shows a selected high order mode, while Figs. 2(B), 2(C), and 2(D) show multiple mode oscillations spatially separated. Moreover, the pro­ posed arrangement can also generate multimode oscillations [Figs. 2(E), 2(F), and 2(G)] almost like an ordinary high Fresnel number spherical resonator. It was also noted that if the aperture were closed and then slowly opened, the first mode to oscillate would have the aspect shown in Fig. 2(H), which is different from the usual Gaussian mode. Finally, resonator alignment of such a configuration was found to be no more critical in similar experimental conditions than that of a piano concave resonator, such as one consisting of a 10-m coupler and a plane mirror. The main interest of a conical resonator is the possibility of selecting a single or a multiple high order circular mode by simple change of the resonator parameters. In combination with the Casperson's method, this new class of resonator should be of great advantage for very large gas lasers, where the geometry of the resonator is of prime importance to get high power output and a relatively good mechanical stabili­ ty.

Journal ArticleDOI
TL;DR: R 5020, a synthetic progestin devoid of androgenic activity, is at least as potent as the most potent 19-nortestosterone derivative, D-norgestrel, in inhibiting gonadotropin secretion and other parameters of the estrous cycle in the rat.

Journal ArticleDOI
TL;DR: In this article, the half-life measurements and branching ratio determinations have been carried out for some T = 1/2 mirror nuclei and the following results have been obtained for the half life and for the branching ratios:
Abstract: Precision half-life measurements and branching ratio determinations have been carried out for some T = 1/2 mirror nuclei. The following results have been obtained for the half-life and for the branching ratios: /sup 13/N (597.9 +- 0.6 s), /sup 15/O (122.23 +- 0.23 s), /sup 17/F (64.31 +- 0.09 s), /sup 21/Na ((95.8 +- 0.2) %), /sup 23/Mg (11.317 +- 0.011 s, (92.2 +- 0.2) %), /sup 25/Al ((99.16 +- 0.04) %), /sup 27/Si ((99.812 +- 0.010) %), /sup 29/P ((98.11 +- 0.30) %), /sup 31/S (2.543 +- 0.008 s, (98.89 +- 0.20) %), /sup 33/Cl (2.507 +- 0.008 s), /sup 35/Ar (1.774 +- 0.003 s, (98.0 +- 0.2) %), /sup 37/K (1.223 +- 0.008 s, (97.8 +- 0.2) %), /sup 39/Ca (0.8594 +- 0.0016 s, > 99.72%).

Journal ArticleDOI
TL;DR: The conversion of cephalothin into a less active metabolite (desacetylcephalothin) might influence its distribution in tissues and the concentrations of antibiotics in subcutaneous fibrin clots in an experimental rabbit model were determined.
Abstract: The conversion of cephalothin into a less active metabolite (desacetylcephalothin) might influence its distribution in tissues. An experimental rabbit model devised to determine concentrations of antibiotics in subcutaneous fibrin clots was used in this study. Groups of five to six animals received 100-mg/kg intravenous injections of either cefamandole or cephalothin. One hour after the injection, the concentration of cefamandole in serum was 20 times higher than that of cephalothin. Whereas cephalothin was undetectable at 4 h, cefamandole was still detectable at the end of the experiment. The half-lives of cephalothin and cefamandole in serum were 16 and 27 min, respectively. The concentration of cefamandole found in fibrin clots was severalfold higher than that of cephalothin. The half-life of cefamandole in clots (81 min) was superior to that of cephalothin (38 min). Although concentrations of both antibiotics were higher in serum than in clots at 1 h, the concentrations of these drugs in the clots persisted at higher levels throughout the next 5 h of the experiment. The extent of binding of cefamandole (87%) to rabbit serum was greater than that of cephalothin (50%). At least 55% of cephalothin was metabolized in vivo into its less active metabolite desacetylcephalothin. This metabolite was found in higher proportion in the serum (75%) than in the clots (55%). Whereas only 12% of the free (unbound) cephalothin reached the clots, 78% of the free cefamandole was found in the clots. This lower level of penetration of unbound cephalothin might be explained by the short half-life of this antibiotic, not permitting equilibrium to occur.