Peripheral plasma progesterone during egg transport in the rabbit.

Peripheral plasma progesterone concentrations were measured in New Zealand rabbits every 6 hr beginning 12 hr before and continuing until 96 hr after either natural mating, hCG injection, or saline injection. The number of ovulation points in naturally mated animals (9.3 +/- 0.6, mean +/- SE) was not significantly different from that in hCG-injected animals (8.6 +/- 1.5). There was a surge in progesterone secretion following both mating and hCG injection. Plasma progesterone concentrations reached a peak prior to ovulation and then fell to basal levels at the time of ovulation. Beginning at approximately 30 hr after the ovulation-inducing stimulus, there was a progressive, significant (P less than 0.001) increase in plasma progesterone concentration, which continued for the duration of the sampling period. The initiation of the postovulatory increase in progesterone secretion corresponds temporally with the movement of eggs from the ampullary-isthmic junction into the isthmus. The progressive increase in plasma progesterone between 30 and 72 hr after the induction of ovulation corresponds with the gradual movement of eggs through the isthmus into the uterus. The data suggest that movement of eggs through the oviductal isthmus is influenced by the postovulatory secretion of progesterone.     

D-galactosamine induced hepatitis in the rabbit: effect on lecithin:cholesterol acyltransferase activity, plasma lipid transfer protein activity and high density lipoproteins

Hepatitis was induced in rabbits by a single intraperitoneal injection of D(+)-galactosamine-HCl (750 mg/kg body wt). Plasma lecithin:cholesterol acyltransferase activity fell to 5% and lipid transfer protein activity to 50% of control values 48 hr after injection. Discoid high density lipoprotein began to appear in plasma of treated rabbits 36 hr after injection, along with populations of high density lipoprotein (HDL) which were both smaller (radius 3.7 nm) and larger (radius 5.9 nm) than the original HDL population (radius 4.8 nm).     

Radiation induced gram negative bacteremia and endotoxemia in rabbits: Modification by anti-lipopolysaccharide hyperimmune equine plasma

Lethal whole body irradiation damages the gut mucosa and leads to leakage of endotoxin or lipopolysaccharides (LPS) into the systemic circulation. Sixteen rabbits, irradiated with 900 rads 60Co, were randomly divided on day 4 into 2 groups, one of which received an intraperitoneal injection of normal saline (control) and the other (experimental) an equal volume of anti-LPS hyperimmune plasma. The time course of endotoxemia and bacteremia were determined for the duration of the experiment. While rabbits in both groups died within 13 days after irradiation, rabbits given saline died on average 2 days earlier, than rabbits given anti-LPS plasma. Plasma LPS concentrations rose to a small peak on day 2 prior to treatment. Thereafter plasma LPS in rabbits given saline increased forty fold by day 9. In contrast, in rabbits given anti-LPS plasma, LPS concentrations in the plasma remained within pretreatment limits (p 0.01). By day 12 after irradiation, plasma anti-LPS IgG had declined to 5.8% of pretreatment levels in rabbits given saline as compared to 46% in rabbits given anti-LPS plasma (p 0.005). Whilst both groups developed gram-positive bacteremia, rabbits given saline in addition also developed gram-negative bacteremia. No rabbits treated with Anti-LPS showed gram-negative bacteremia. Treatment with Anti-LPS plasma thus significantly protects radiated rabbits from the incidence of gram-negative bacteremia, development of high plasma LPS levels and hence endotoxemia, and prolongs survival to a certain extent.     

Suppression of plasma thyroid hormone concentrations by cortisol in the European eel Anguilla anguilla

Female European eels, Anguilla anguilla, were given a single intra-arterial injection via a catheter of cortisol hemisuccinate at doses ranging from 3.5 to 35 micrograms (15 to 150 micrograms/kg body wt), yielding mean plasma cortisol levels of 87-410 ng/ml 2 hr after injection. Cortisol treatment (17.5 and 35 micrograms) significantly decreased plasma levels of thyroxine (T4) and triiodothyronine (T3) within 24 hr relative to those in control fish. Cortisol treatment (35 micrograms) appeared to increase the clearance rate of 125I-T3 from plasma and the proportionate uptake of radioactivity in certain tissues after injection of 125I-T3. Cortisol treatment had no apparent effect on the plasma clearance of 125I-T4 or tissue distribution of radioactivity after injection of 125I-T4.     

Effect of endotoxin on plasma albumin and fibrinogen synthesis rates in rabbits as measured by the [14C]carbonate method

1. Rates of synthesis of plasma albumin and fibrinogen were measured by the [(14)C]carbonate method in normal rabbits and in animals that received a single intravenous injection of Shigella endotoxin 14-48hr. earlier. 2. The accuracy of the method was improved by introducing refinements into procedures for measuring (14)C radioactivities associated with both urea and proteins that are lost from the plasma during the synthesis interval. 3. The synthesis interval (time between injecting carbonate and measuring specific radioactivities of protein guanidine carbon in plasma) can be shortened with advantage to 3-4hr. 4. Injection of endotoxin markedly decreased the fractional rate of loss in the first few hours of injected radioiodine-labelled fibrinogen and to a smaller extent of similarly labelled albumin from the plasma. The absolute rate of synthesis of fibrinogen was increased in endotoxin-treated rabbits by more than 400% compared with normal animals, and the rate of synthesis of albumin was increased by about 60%.     

Movement of horseradish peroxidase in rabbit submandibular glands after ductal injection

Synopsis Horseradish peroxidase (HRP) has been used as a tracer to study movements of solutions injected retrogradely via the duct of submandibular glands in rabbits. 0.1 ml of solution was injected either manually or by a constant hydrostatic pressure, and the subsequent distribution of HRP in the gland and duct at different times after injection has been examined histochemically at light and electron microscopical levels.Shortly after the injections, strong interstitial staining for peroxidase resulted from passage between acinar cells. Some sites of cellular uptake were observed and staining occurred in some ductal cells even when the duct had been cut at the hilum to minimize pressure effects. It is not known whether this diffuse uptake represents a physiological or pathological phenomenon. Some interstitial activity still remained 24 hr after injection but had disappeared by 48 hr. Inflammatory cells first appeared in the gland about 4 hr after the injection and slowly increased up to about 24 hr after injection.The results indicate that the HRP reaches the interstices of the gland principally by penetration between acinar cells, and that the junctional complexes between striated duct cells appear to be more resistant to disruption by luminal pressures.     

Cachectin/tumor necrosis factor: production, distribution, and metabolic fate in vivo

A highly specific radioreceptor assay for cachectin/tumor necrosis factor (TNF) was utilized to measure the time course of lipopolysaccharide (LPS)-induced hormone production in rabbits. Cachectin/TNF bioactivity was monitored in the same serum samples by measuring lipoprotein lipase (LPL) suppression in 3T3-L1 cells. Cachectin/TNF is produced in large quantities by LPS-treated rabbits without priming by bacillus Calmette Guérin, C. parvum, or other agents. Nanomolar concentrations of the hormone are achieved, with peak levels occurring at 2 hr postinjection; the hormone is rapidly cleared thereafter. In separate studies, mice were used to assess the distribution and metabolic fate of cachectin/TNF. Radioiodinated hormone is cleared from the plasma with a half-life of 6 to 7 min. Studies of the tissue distribution of label after injection demonstrate that liver, kidneys, skin, and gastrointestinal tract take up most of the hormone. Electrophoretic analysis of tissues recovered from injected animals suggests that the hormone is very rapidly degraded after binding.     

Pharmacokinetics of triclabendazole in rabbits

1.Pharmacokinetic profiles of triclabendazole (TCBZ) following intravenous (i.v.) and oral administration of the drug in rabbits were carried out.2. In normal rabbits, TCBZ was metabolized rapidly to its sulphoxide (TCBZ-SO) and sulphone (TCBZ-SO₂) derivatives following administration, with undetectable concentrations of unchanged TCBZ in the plasma of the treated animals at any time (detection limit, 10 ng/ml).3. The disposition kinetics of this drug in rabbits can be described by a two-compartment open model.4. Mean peak concentrations in plasma of TCBZ-SO and TCBZ-SO₂ of 12.41 μg/ml and 9.5 μg/ml occurred 7.5 and 9.5 hr after oral administration, respectively.5. Both metabolites were eliminated slowly from plasma with elimination half-lives of 16.86 hr for the sulphoxide and 13 hr for the sulphone.6. The area under the plasma concentration versus time curve (AUC) was 240 mg hr/l for the sulphoxide, higher than that found for the sulphone, 185 g hr/l.     

The incorporation of isotopic carbon (14C) into the cerebral glycogen of rabbits

1. The incorporation of (14)C into the brain glycogen of conscious rabbits with labelled glucose, bicarbonate and glutamate as precursors has been studied. 2. Substantial incorporation from all these precursors was demonstrated after an interval of 5hr. from their injection. 3. With [(14)C]glucose maximal incorporation occurred at about 8hr. from the time of injection. 4. Hydrocortisone led to increased incorporation of (14)C from labelled glucose. 5. Some comparisons between the turnover of brain glycogen and that of skeletal and cardiac muscle are reported.     

Involvement of hypothalamic somatostatin in glucagon-induced suppression of growth hormone secretion in conscious rats

The role of central glucagon in regulating GH secretion was studied in conscious male rats with chronic indwelling intra-atrial and intracerebro-ventricular (ICV) cannulae. Repeated blood sampling every 20 min from 1000 hr to 1700 hr showed two major GH bursts occurring at regular intervals (3.6±0.1 hr) around 1200 hr and 1540 hr. The ICV (lateral ventricle) injection of glucagon (10 μg/rat) at 1100 hr inhibited spontaneous GH secretion, and the mean (±SE) plasma GH levels from 1120 hr to 1700 hr were lower than those in controls injected ICV with the vehicle solution only (31.9±7.8 ng/ml vs. 157.1±13.4 ng/ml, p<0.01). The GH bursts did not appear until 5 hr after the injection. The intravenous (IV) injection of glucagon (10 μg/rat) did not change plasma GH levels or the occurrence of spontaneous GH bursts. The glucagon-induced suppression of GH release was attenuated when anti-somatostatin serum (ASS), but not normal rabbit serum (NRS), was given IV in a volume of 0.25 ml immediately before the ICV injection of glucagon (10 μg/rat) (mean GH levels at 1120–1700 hr: ASS+glucagon, 133.6±26.7 ng/ml vs. NRS+glucagon, 30.5±7.4 ng/ml, p<0.01). These findings suggest that central glucagon may play an inhibitory role in regulating GH secretion by stimulating SRIF release from the hypothalamus in the rat.     

Movement of lipids into and out of the blood during hyperlipidemia induced in rabbits by pituitary extract and fraction H

Rabbits were rendered hyperlipidemic by the subcutaneous injection of an alkaline aqueous extract of mammalian pituitary gland or a partially purified, concentrated fraction derived therefrom, designated Fraction H. Eight hours after the injection of Fraction H, arteriovenous (A-V) differences in plasma triglyceride (TG) were measured across five body areas. A large negative A-V difference in plasma TG was consistently found across the liver (increase in plasma concentration), and a moderate positive A-V difference across the perirenal fat depot (decrease in plasma concentration). Most values obtained across the intestines and mesentery and the leg were positive. Differences across the kidney were mostly small and almost equally divided between positive and negative values. Similar results were obtained 7-12 and 16-18 hr after injection of the pituitary extract. It is concluded that the liver is the principal source of the TG for this kind of hyperlipidemia, and that the plasma TG levels are reduced principally in passage through adipose tissue. A consistent negative A-V difference in plasma free fatty acid concentration (net increase) was found across the kidney 7-12 hr after injection, suggesting that the kidney hydrolyzes its accumulated TG and mobilizes it in the form of free fatty acids.     

Effects of Desacetyl-alpha-MSH on Lipid Mobilization in the Rainbow Trout, Oncorhynchus mykiss

Effects of melanocyte-stimulating hormone (MSH) and beta-endorphin on lipid mobilization were examined in the rainbow trout (Oncorhynchus mykiss). Plasma levels of fatty acid (FA) were measured after intra-arterial administration of alpha-MSH, desacetyl-alpha-MSH, beta-MSH, or beta-endorphin through a cannula in the dorsal aorta. Desacetyl-alpha-MSH at 1 ng/g body weight resulted in an increase in plasma FA levels 1-3 hr after the injection, whereas the other three peptides showed no significant effect at the same dose. There was no significant change in plasma levels of cortisol after administration of any of the peptides. Lipolytic enzyme activity in the liver was significantly increased in a dose-related manner 1 hr after single intra-peritoneal injection of desacetyl-alpha-MSH. The direct effect of desacetyl-alpha-MSH on lipolysis was examined in liver slices incubated in vitro. Lipase activity in the liver slice was stimulated in the medium containing desacetyl-alpha-MSH in a dose-related manner. The results indicate that desacetyl-alpha-MSH is a potent stimulator of lipid mobilization in the rainbow trout.     

Plasma concentration of progesterone during normal estrous cycles and following prostaglandin F(2alpha) treatment of Bos indicus and tropic-adapted Bos taurus heifers

The introduction of the use of prostaglandin F(2alpha) (PGF(2alpha)) to synchronize estrus in cattle adapted to the tropics suggests a need to investigate the endocrine response to this treatment. Progesterone (P) concentrations in blood plasma of Bos indicus and tropic-adapted Bos taurus heifers during normal estrous cycles and following estrus synchronization were compared. After PGF(2alpha) administration, the heifers were divided into two groups on the basis of response to treatment. Mean P levels in heifers showing estrus after the first injection ranged from 1.0-3.0 ng/ml, decreasing to 0.2-0.4 ng/ml 24 to 48 hr after treatment. The second group exhibited estrus only after the second PGF(2alpha) injection and had low P (0.2-0.9 ng/ml) in plasma before the first injection. Mean peak P levels in both groups 8 to 12 d after the first injection in the periestrous period were not different from values in the same heifers at similar periods of the preceding control estrous cycle. Neither the tropical location nor breed affected the luteolytic effect of PGF(2alpha).     

A novel explanation for the reduced LDL cholesterol in severe hypertriglyceridemia

When [3H]cholesteryl ester-labeled low density (LDL) and intermediate density lipoproteins (IDL) from a normotriglyceridemic, hypercholesterolemic rabbit were injected into severely hypertriglyceridemic, hypercholesterolemic rabbits, 60% of the label appeared in very low density lipoproteins (VLDL) at 3 hr. A similar experiment showed that 40% of injected 131I-protein-labeled LDL appeared in the IDL fraction at 4 hr. Taken together, these data suggest that the exchange of LDL cholesteryl ester for VLDL triglyceride results in a density shift of injected LDL to the IDL density range. Furthermore, the percent of injected 131I-labeled LDL from normotriglyceridemic rabbits that appeared in the IDL fraction increased in rabbits with increasing levels of plasma triglyceride. This LDL density shift was reproduced in vitro by incubating iodinated LDL from normotriglyceridemic, hypercholesterolemic rabbits with concentrations of VLDL from hypertriglyceridemic, hypercholesterolemic rabbits similar to those in plasma. With such a system, it was shown that the percentage of LDL that appeared in the IDL fraction increased with time, was enhanced fourfold by the addition of plasma lipid transfer protein, increased with increasing molar ratio of triglyceride to cholesteryl ester in VLDL, but apparently did not increase with increasing VLDL particle number. These studies suggest that a pronounced decrease in density of lipoproteins that would normally appear in the LDL density range, resulting from loss of cholesteryl ester in exchange for VLDL triglyceride, may explain, at least in part, the reduced LDL levels in severe hypertriglyceridemia.     

Metabolism of apoB-100 in lipoproteins separated by density gradient ultracentrifugation in normal and Watanabe heritable hyperlipidemic rabbits

We have examined the capability of a previously developed compartmental model to explain the kinetics of radioiodinated apolipoprotein (apo) B-100 in very low density lipoproteins (VLDL), intermediate density lipoproteins (IDL), and low density lipoproteins (LDL) separated by density gradient ultracentrifugation after intravenous injection of radioiodinated VLDL into New Zealand white (NZW) and Watanabe heritable hyperlipidemic (WHHL) rabbits. Our model was developed primarily from kinetics in whole blood plasma of apoB-100 in particles with and without apoE after intravenous injection of large VLDL, total VLDL, IDL, and LDL. When the initial conditions for this model were assumed to be an intravenous injection of radiolabeled VLDL, the plasma VLDL and LDL simulations for NZW rabbits and the VLDL, IDL, and LDL simulations for WHHL rabbits were found to be inconsistent with the observed density gradient data. By adding a new pathway in the VLDL portion of the model for NZW rabbits and a new compartment in VLDL for WHHL rabbits, and by assuming some cross-contamination in the density gradient ultracentrifugal separations, it was possible to bring our model, which was based upon measurements of 125I-labeled apoB-100 in whole plasma, into conformity with the data obtained by density gradient ultracentrifugation. The relatively modest changes required in the model to fit the gradient ultracentrifugation data support the suitability of our approach to the kinetic analysis of the metabolism of apoB-100 in VLDL and its conversion to IDL and LDL based upon measurements of 125I-labeled apoB-100 in whole plasma after injection of radiolabeled VLDL, IDL, and LDL. Furthermore, the differences in kinetics observed by us between data from whole plasma and data from plasma submitted to ultracentrifugal separation from the same or similar animals highlight the fact that small variations that can occur in the separation of lipoprotein classes by buoyant density can lead to confusing results.     

Somatostatin immunoneutralization affects plasma metabolite concentrations in the domestic fowl

Young leghorn cockerels were injected with antiserum to somatostatin (anti-SRIF) and plasma glucose, free fatty acids and alpha-amino nitrogen concentrations determined. Plasma glucose concentrations increased rapidly after anti-SRIF and remained high for up to 2 hr. Two different antisera tested had hyperglycaemic activity. Plasma free fatty acids also increased rapidly after administration of the two different anti-SRIFs, and remained high for about 1 hr. Plasma alpha-amino nitrogen increased during the first 30 min after anti-SRIF, then declined to levels significantly lower than control by 1-2 hr after injection. Anaesthesia reduced plasma concentrations of glucose and alpha-amino nitrogen, and also reduced the changes of these metabolites following anti-SRIF. The results show the importance of endogenous somatostatin in the regulation of plasma metabolite concentrations.     

Parallel changes in plasma cholesterol and lipid transfer activity in pregnant rabbits

The relationship between the concentration of plasma cholesterol and the lipid transfer activity (LTA) of lipoprotein-deficient plasma (d greater than 1.21) was studied in two models of pregnancy in the rabbit. Plasma cholesterol and the protein-mediated transfer of cholesteryl ester and triglyceride were monitored throughout gestation, 48 hr after parturition, and during lactation in New Zealand white (NZW) and heterozygous WHHL rabbits. Lipoprotein cholesterol was determined prior to and 48 hr after parturition. For both NZW and heterozygous WHHL rabbits, the progressive hypocholesterolemia of gestation was associated with parallel changes in LTA. Similarly, the rapid postpartum increase in plasma cholesterol was paralleled by increased LTA for both strains. In relation to basal values, the relative changes in plasma cholesterol and LTA were virtually identical. These data provide further evidence that in the rabbit plasma cholesterol and LTA are closely related.     

The effect of beta-naphthoflavone on rabbit liver protein synthesis, and on the induction of cytochrome P-450 LM4 mRNA

A single injection of β-naphthoflavone dispersed in corn oil causes significant changes in rabbit liver polysome and polysomal poly(A+)mRNA driven $\text{in vitro}$ protein synthesis. The changes occur between 6–18 hr and 30–36 hr after the injection. Our data indicate that the first effect is due to the β-naphthoflavone and the second effect is due to the oil vehicle. $\text{In vitro}$ translation of rabbit liver polysomes obtained from treated rabbits followed by specific immunoprecipition and gel electrophoresis, showed that maximal levels of translatable cytochrome P-450 LM₄ occurred 18–24 hr after β-naphthoflavone treatment.     

Ultimate Fate of Rod Outer Segments in the Retinal Pigment Epithelium

To investigate the degradation pathway of rod outer segments (ROS) in vivo, we injected gold-labeled ROS into the subretinal space of rabbits using a pars plana approach. Histology and electron microscopy performed on the specimens 72 hr after ROS injection revealed that the retina over the injection site was reattached, the retinal pigment epithelial (RPE) cells were intact, and gold granules were localized inside melanin granules and melanosomes. These results indicate that, in RPE, in vivo degradation of ROS is associated with melanosomes.     

Ultimate fate of rod outer segments in the retinal pigment epithelium.

To investigate the degradation pathway of rod outer segments (ROS) in vivo, we injected gold-labeled ROS into the subretinal space of rabbits using a pars plana approach. Histology and electron microscopy performed on the specimens 72 hr after ROS injection revealed that the retina over the injection site was reattached, the retinal pigment epithelial (RPE) cells were intact, and gold granules were localized inside melanin granules and melanosomes. These results indicate that, in RPE, in vivo degradation of ROS is associated with melanosomes.