Postinjection Hours Research Articles

Effects of intracameral injection of tissue plasminogen activator on corneal endothelium and intraocular pressure in dogs

Summary Contact wide-field specular microscopy was performed on eyes of 16 healthy dogs after tissue plasminogen activator at a concentration of 25 μg/100 μl (group 1, n = 8) or 50 μg/100 μl (group 2, n = 8) was injected into 1 anterior chamber of each dog. The contralateral eye served as a nontreated control. Applanation tonometry was used to measure intraocular pressure in both eyes for up to 168 hours. By use of computerized morphometric analysis and pachymetry, changes from baseline values in endothelial cell density, cell morphologic features, and corneal thickness were evaluated at postinjection hours 24, 48, and 168. Significant mean differences in intraocular pressure were not detected between treated eyes of group-1 dogs and those in group 2 at designated times, or between treated and nontreated eyes of dogs in either group. Mean corneal thickness of treated and nontreated eyes was similar in both groups through postinjection hour 168. Changes in mean percentage of endothelial cell sides were observed only in treated eyes of group-2 dogs, with the mean percentage of hexagons at postinjection hour 168 decreasing by 18%, a decrease that was significantly (P < 0.05) greater than the decrease in nontreated eyes. The mean percentage of 6-sided cells in treated eyes of group-2 dogs was significantly (P < 0.05) less than that in treated eyes of group-1 dogs at postinjection hour 168.

The effects of amphetamine on body weight and energy expenditure

Although there is evidence suggesting that, in addition to suppressing food consumption, amphetamine reduces body weight by increasing energy expenditure, there is little consistency among the few studies examining that factor. In this experiment, the effect of amphetamine on daily energy consumption, within-day body weights, and hourly measures of metabolic rate (MR) and respiration quotient (RQ) were assessed. Daytime drug injections decreased total energy consumption, produced biphasic changes over time in MR, and persistently lowered RQ values. In contrast, nighttime injections of drug had little effect on energy consumption and MR but did reduce RQ for the first 4 postinjection hours. These effects show that amphetamine effects interact with the circadian organization of behavior and suggest that rodent studies of anorectic agents have more relevance for humans if drugs are given during the night, when rats are normally awake and eating. From this study, it seems clear that amphetamine reduces body weight by altering metabolic rate and fat metabolism in rats when the drug is given during the day.

Inhibition of growth hormone-releasing factor suppresses both sleep and growth hormone secretion in the rat

To study the possible involvement of hypothalamic growth hormone-releasing factor (GRF) in sleep regulation, a competitive GRF-antagonist, the peptide ( N-Ac-Tyr 1, D-Arg 2)-GRF(1–29)-NH 2, was intracerebroventricularly injected into rats (0.003, 0.3, and 14 nmol), and the EEG and brain temperature were recorded for 12 h during the light cycle of the day. Growth hormone (GH) concentrations were determined from plasma samples taken at 20-min intervals for 3 h after 14 nmol GRF-antagonist. The onset of non-rapid eye movement sleep (NREMS) was delayed in response to 0.3 and 14 nmol GRF-antagonist, the duration of NREMS was decreased for one or more hours and after 14 nmol EEG slow wave amplitudes were decreased during NREMS in postinjection hour 1. The high dose of GRF-antagonist also suppressed REMS for 4 h, inhibited GH secretion, and elicited a slight biphasic variation in brain temperature. These findings, together with previous observations indicating a sleep-promoting effect for GRF, support the hypothesis that hypothalamic GRF is involved in sleep regulation and might be responsible for the correlation between NREMS and GH secretion reported in various species.

Cholecystokinin promotes sleep and reduces food intake in diabetic rats

It has been reported that systemic injections of cholecystokinin (CCK) elicit the behavioral characteristics of satiety, including sleep, in rats. CCK is a potent stimulator of insulin secretion, and insulin is hypothesized to be involved in sleep and feeding regulation. The purpose of the current experiments was to study the possible role of endogenous insulin in the food-intake-reducing and hypnogenic effects of intraperitoneally (IP) administered CCK. Normal and streptozotocin (STR)-diabetic rats were injected with isotonic saline or CCK (10 and 50 μg/kg) at dark onset, and sleep-wake activity was determined for the next 12 h. There were no significant differences between the baseline sleep-wake activity of normal and diabetic rats. IP injection of CCK elicited a selective increase in nonrapideye-movement sleep in both groups during the first postinjection hour. In a separate experiment, the effects of CCK (10 μg/kg) on food intake were determined in control and diabetic rats; CCK suppressed the 1-h food intake in both groups. In a third experiment, the effects of CCK treatment (50 μg/kg) on plasma insulin levels were determined. In normal rats, CCK elicited a two-fold increase in plasma insulin concentration, whereas diabetic rats had a significantly lower basal insulin level which was not affected by CCK treatment. We conclude that hypnogenic and food-intake-reducing effects of exogenously administered CCK are closely associated; however, pancreatic insulin does not play a significant role in either of these effects.

Interleukin 1-receptor antagonist blocks interleukin 1-induced sleep and fever

The recent purification and characterization of an interleukin 1-receptor antagonist (IL-1ra) has provided an additional means of elucidating the mechanisms involved in the responses initiated by IL-1. Central administration of IL-1 to rabbits results in a characteristic febrile response and in increased non-rapid-eye-movement sleep (NREMS). In this study, rabbits received various doses of IL-1ra (10-1,000 micrograms) or pyrogen-free saline intracerebroventricularly, and sleep-wake activity and brain temperature (Tbr) were determined for the next 24 h. All doses of IL-1ra tested tended to reduce NREMS in the first postinjection hour with little effect on Tbr. When rabbits were pretreated with 100 micrograms IL-1ra and then injected with 10 ng IL-1, the characteristic IL-1-induced febrile and NREMS-promoting effects were completely blocked.

Horseradish peroxidase study of the location of extrinsic efferent and afferent neurons innervating the colon of dogs

SUMMARY The abdominal portion of the colon of 13 clinically normal dogs was divided into 5 regions (ascending, transverse, left colic flexure, proximal descending, and distal descending), and each region was injected with 30 mg of horseradish peroxidase (hrp). The injected colonic region, brain stem, L7-Cd1 portion of the spinal cord, sympathetic trunk ganglia, celiacomesenteric ganglia, caudal mesenteric ganglion, pelvic plexi, distal vagal (nodose) ganglia, and Ll-Cdl spinal ganglia were obtained at postinjection hour 48, sectioned, and processed by use of the tetramethylbenzidine method. The entire length of the colon was found to be under extrinsic influence of the parasympathetic nucleus of cranial nerve X (px), with the largest average number of labeled cells resulting from injection of the ascending colon. It was also indicated that the entire colon is under extrinsic influence of the sacral portion of the spinal cord because the pelvic ganglia (second-order neurons) of the pelvic plexi contained labeled cells for all colonic regions. The largest average number of labeled cells in pelvic ganglia was seen after injection of the distal portion of the descending colon. Only after injection of the distal portion of the descending colon were labeled cells found in the S1-S3 portion of the spinal cord. Labeled cells in the px, spinal cord, and pelvic ganglia were found bilaterally. Although the entire abdominal portion of the colon appears to be influenced by cranial and sacral parasympathetic preganglionic (via pelvic ganglia) neurons, the relative importance of the 2 areas seems to be reversed between the ascending colon and distal portion of the descending colon. Sympathetic postganglionic innervation was located in the celiacomesenteric ganglion, caudal mesenteric ganglion, and, inconsistently, in sympathetic trunk ganglia. Sensory innervation for all colonic regions was found bilaterally in the distal vagal ganglia, and in 2 groups of spinal ganglia—a cranial group of LI to L5 and a caudal group of S1 to Cd1 ganglia. It has been reported in the literature that the left colic flexure is subject to colonic perforation in dogs with spinal cord disease treated with corticosteroid administration, but a direct, anatomic reason for this site of susceptibility was not found during this study. It is possible that the left colonic flexure represents the most proximal portion of colon detrimentally affected by loss of sacral influence, because the relative importance of vagal and sacral parasympathetic innervation appears to shift along the length of the colon.

Effects of intracameral injection of viscoelastic solutions on corneal endothelium in dogs

SUMMARY Contact in vivo wide-field specular microscopy was performed on right eyes of 20 healthy dogs after sodium hyaluronate (1%, n = 5), sodium chondroitin sulfate (4%) and sodium hyaluronate (3%, n = 5), hydroxypropyl methylcellulose (2%, n = 5), or balanced salt solution (control, n = 5) was injected into the anterior chamber. Using computerized morphometric analysis and pachymetry, changes in endothelial cell density, cell morphologic features, and corneal thickness from baseline values were evaluated at postinjection hour (pih) 72 and pih 168. Changes were not seen in endothelial cell density or cell morphologic features in any treated eye. The mean corneal thickness of all treated eyes at pih 72 increased 6%, significantly greater than that of the nontreated eyes (P = 0.03). Mean corneal thickness of treated and nontreated eyes was similar at baseline and pih 168 in all treatment groups.

Phagocytosis, bactericidal activity, and oxidative metabolism of milk neutrophils from dairy cows fed selenium-supplemented and selenium-deficient diets

SUMMARY Six primiparous Holstein cows were fed a Se-deficient diet, beginning at least 90 days before their first calving, and 6 other primiparous cows were given the same diet plus a supplement of 2 mg of Se/cow/d as sodium selenite. All cows were fed their diets for the duration of the experimental period. One uninfected quarter of each cow was injected with 25 μg of Escherichia coli endotoxin at postpartum week 5. Leukocytes were isolated by centrifugation from milk collected at postinjection hour 16. Isolated cells were 92 ± 3% neutrophils and were incubated with Staphylococcus aureus or E coli in a 1:300 ratio. Phagocytosis and intracellular killing by neutrophils were assessed after 0, 30, 60, and 90 minutes by a fluorochrome assay, using acridine orange. Viability of neutrophils was assessed by use of trypan blue. Superoxide anion production and hydrogen peroxide production by neutrophils also were determined. Cows fed Se-deficient diets had significantly (P < 0.05) lower blood Se concentration and blood glutathione peroxidase activity than cows fed Se-supplemented diets. Selenium status had no effect on the phagocytic capacity of neutrophils. Neutrophils obtained from cows fed Se-supplemented diets killed a significantly (P < 0.05) higher percentage of ingested bacteria than did neutrophils from cows fed the Se-deficient diet. Viability was significantly (P < 0.05) reduced by incubation with S aureus in neutrophils from both groups of cows, with neutrophils from Se-deficient cows having lower viability. Superoxide anion production did not differ significantly between neutrophils from the 2 groups, but extracellular hydrogen peroxide concentration was significantly (P < 0.05) higher in neutrophils harvested from milk of cows fed the Se-deficient diet.

Effects of Serotonin on the Food Intake in Chickens in the Early Post-hatching Period

Baranyiova Eva: Effects of Serotonin on the Food Intake in Chickens in the PostHatching Period. Acta vet. Brno, 59, 1990: 23-33. The effect of serotonin (5-HT) on food intake in the post-hatching period was studied in 360 Hybro broilers from 1 to 25 days of age in 3 experimental series. They were reared in batteries and had free access to food and water. The experimental chickens (4 groups of 10 or 20 birds) were each intraperitoneally given single doses of 1 or 2 mg 5-HT (Sigma Corp., USA), four groups were sham-injected with saline, and four groups were left untreated. The food intake of experimental and control groups was measured 30 and 60 min post injection and then at 1-h intervals till 1400 h. Cumulative food intake for the interval 0700 to 1400 h and per 24 h was also recorded. The 5-HT administration did not affect the food intake of chickens 1 and 2 days of age. On day 3, however, the birds began to respond to 5-HT administration in that its higher dose stopped eating in the first post-injection hour, the lower dose (1 mg . kg-I) suppressed it significantly as compared to sham-injected (P < 0.01) and intact controls (P < 0.02). The food intake of experimental chickens at all other ages under study (i. e. on days 4, 5, 9,11,17 and 25) was similarly suppressed in the first post-injection hour compared to either control groups. No dose-dependent effect of 5-HT was detected. In older birds, consuming increasingly larger portions in the first morning hour, the 5-HT induced abstinence was also manifested in cumulative food intake from 0700 to 1400 h. Their actual food consumption was lower at 17 (P < 0.01) and 25 (P < 0.01) days of age, the relative food intake at 17 (P < 0.01) days. Expressed in terms of 24-h consumption the 5-HT inhibited eating during the first morning hour became apparent especially in 25-d-old birds (P < 0.05). It is noteworthy that no differences in food consumption of sham-injected and intact controls were found. The fact that the ingestive response to peripheral administration of 5-HT did not occur until day 3 suggests that maturation of some components of the serotoninergic system in the fowl continues after hatching. Age, broiler, intraperitoneal administration, 5-HT In birds, serotoninergic mechanisms are involved in the regulation of numerous physiological functions. Their morphological substrates and the presence of serotonin (5-HT) in various tissues have been demonstrated (Juorio and Vogt 1967; Epstein et al. 1980; Gershon et al. 1980; Cassone et al. 1983; Wallace 1985). In the blood plasma of cocks 3-7 mg. kgl have been found (Freeman 1984). A number of studies on 5-HT have shown that this neurotransmitter affects the cardiovascular and respiratory systems of pigeons and poultry, exerts an excitatory effect on the electromyographic activity of the esophagus of the adult pigeon, and is involved in energy metabolism and thermoregulation affecting their circadian rhythms in chickens (Cogburn et al. 1976; Freeman 1979; Hillman et al. 1980; Fileccia et al. 1987; Hohtola et al. 1989). Serotonin administered centrally or peripherally also affects the behaviour of birds; in chickena

Prolactin, vasoactive intestinal peptide, and peptide histidine methionine elicit selective increases in REM sleep in rabbits

The purpose of these experiments was to determine whether (1) vasoactive intestinal peptide (VIP) produces effects on rabbit sleep similar to those reported for rats and cats; (2) peptide histidine methionine (PHM), a peptide closely related to VIP, mimics the sleep effects of VIP; and (3) pituitary prolactin (PRL), a pituitary hormone that has a sleep-related secretory pattern and for which VIP and PHM act as releasing factors, has similar effects on sleep. VIP or PHM (0.01, 0.1 and 10. nmol/kg) was intracerebroventricularly (i.c.v.) injected; PRL (ovine PRL, 45 and 200 IU/kg) was subcutaneously (s.c.) administered. Sleep-wake activity and brain temperature were recorded for 6 h. For controls, rabbits received artificial cerebrospinal fluid i.c.v. or PRL-vehicle s.c. VIP and PHM promoted rapid eye movement sleep (REMS), although these effects were not dose-dependent. In addition, the high dose of VIP and PHM transiently increased wakefulness. Increases in REMS occurred only during hours 2–6 after i.c.v. injection of VIP and peptide histidine leucine (PHI). After s.c. injection of PRL, REMS started to increase in postinjection hour 3. The effect of the high dose was significantly more pronounced than that of the small dose. Each substance enhanced the frequency of REMS episodes, and the high dose of PRL also increased the duration of REMS bouts. These results are consistent with the hypothesis that VIP is involved in physiological regulation of REMS, and that the VIP- and PHM-induced increases in REMS may be mediated via release of PRL.

Effects of nocturnal intraperitoneal administration of cholecystokinin in rats: simultaneous increase in sleep, increase in EEG slow-wave activity, reduction of motor activity, suppression of eating, and decrease in brain temperature

Rats received an i.p. injection of cholecystokinin-octapeptide sulfate ester (CCK; 4, 10 or 50 μg/kg) or physiological saline at dark onset, and the 24-h sleep-wake cycle (12-h-dark and 12-h-light phases), spontaneous motor activity and brain temperature ( T br) were recorded. EEG activity was studied through spectral analysis for 2.5 h, and food intake was measured at the end of postinjection hour 1. In response to CCK, non-REM sleep increased at the expense of wakefulness, and the sleep-promoting effect was substantiated by an increase in EEG slow-wave activity. Motor activity, T br and food intake decreased. The effects vanished in postinjection hour 2; the diurnal rhythms were not modified. The changes varied as a function of the dose: the effects were significant following 10 μm/kg, and even higher in response to 50 μg/kg CCK. The results indicate that i.p. CCK definitely promotes non-REM sleep. This effect may belong to the behavioral sequence elicited by the peptide, which is often attributed to satiety. As evidenced by the reduction of T br CCK also exerts strong autonomic actions, which might interfere with the behavioral responses.

The effects of delta-sleep-inducing peptide (DSIP) on wakefulness and sleep patterns in the cat

The effect of a single injection of synthetic delta-sleep-inducing peptide (DSIP, 7 nmol/kg) into the lateral ventricle of 10 cats was investigated by monitoring the sleep-wake cycle during an 8 h period. A significant decrease in sleep latency and a significant increase in total sleep and in total slow wave sleep (SWS) was found following DSIP administration. The increase in sleep resulted exclusively from a significant increase in deep slow wave sleep (S 2), while light slow wave sleep (S 1) was significantly decreased. Neither the total amount of REM sleep, nor hourly values of REM sleep were affected by DSIP application. Additional measures of REM sleep, like REM sleep latency, mean episode number and mean episode length were not different from those found in control conditions. DSIP was immediately effective since the amount of S 2 increased to more than 50% in the first postinjection hour and the difference from the control value was highly significant. The increase in S 2 was maintained over 7 h, and disappeared by the eighth hour. The increase in S 2 was caused by a prolongation of S 2 episodes and not by their more frequent occurrence. The results obtained suggest a sleep-facilitating property of DSIP.

Administration of low doses of TSH result in a rapid increase in the metabolic rate of young lambs.

A low dose of TSH (Thyroid Stimulating Hormone) can induce a rapid increase in VO2 and the response is dose dependent. Lambs aged 36 to 289 h were used. 5.0 i.u./kg TSH, the highest dose used, caused an initial inhibition of response but during the second and third post injection hours VO2 increased to control level. The intermediate TSH dose, 1.0 i.u./kg TSH resulted in a clear increase in VO2 even in the first post-injection hour, which further increased in the second and third hours. This change was significantly greater than in controls. Animals treated with the lowest dose, 0.5 i.u./kg TSH divided themselves into 2 distinct populations: responders, where an immediate and significant increase in VO2 occurred and non responders, where a small inhibition of metabolism was evident. The responder group had a significantly lower pre-injection VO2 and a significantly lower mean body weight, than the non responders. In the responders, the stimulation of metabolism was greater than at either of the higher TSH doses. These results indicate that low, but not high doses of TSH induce a rapid metabolic response. The argument in favour of a short-term role for thyroid hormones is thus strengthened.

Low Doses of T3Induce a Rapid Metabolic Response in Young Lambs

Injection of 1 microgram/kg T3 resulted in an increase in metabolic rate (VO2) within an hour of administration to lambs (aged 27 to 180 h). A larger dose of 5 micrograms/kg T3 initially caused a slight inhibition of VO2, which was followed in the second post-injection hour by a significant increase. The increase in VO2 during the second post-injection hour after either 1 microgram/kg or 5 micrograms/kg T3 represented a rise of 22% above pre-injection VO2. The increase persisted and was slightly enhanced during the third post-injection hour. These changes were significantly greater than the smaller changes which followed control injection (P less than 0.005). No significant changes in Tre or Tesk occurred after any treatment. This rapid response to low, physiological doses of T3 emphasises a possible role for thyroid hormones in the short-term control of metabolism in young animals.

Neurochemical effects of ethylhexyl nitrate in rats

Rats injected i.p. with 100 mg ethylhexyl nitrate/kg body wt excreted 0.3% of the dose in the urine within 24 h. No urinary nitrite was found within 5 postinjection hours while an output of 26.9 ± 15.8 μg nitrite/h × kg body wt. was detected between 5–24 h. Cerebral glutathione concentration was below the control level after 1 day but returned to control value after 3 and 7 days postinjection. Brain acetylcholine esterase activity was marginally decreased after 1 day while RNA and succinate dehydrogenase assay excluded major structural damage. It seems that the mechanism of clinical symptoms experienced by exposed workers are comparable to those exposed to dynamite and are largely functional.

Serum phenobarbital and barbital concentrations in rats on a limited food regimen

Serum barbiturate levels were tracked for several hours in food deprived rats given 40, 60 or 80 mg/kg (SC) of either phenobarbital or barbital. All 3 phenobarbital doses produced peak serum drug levels at 1.5 hr postinjection. Serum barbital concentrations peaked 3 hr after both 60 and 80 mg/kg barbital doses while the 40 mg/kg dose produced a stable low drug level throughout the 4 postinjection hours. For both barbiturates administered, 40 mg/kg doses produced lower serum drug levels than either 60 or 80 mg/kg. The differences in serum drug concentrations between the latter two dose levels were inconsistent over time.

Hypophagia follows the initial hyperphagia produced by 2-deoxy-D-glucose in rats

The glucose analogue 2-deoxy-D-glucose (2DG) inhibits glucose metabolism and causes a rapid increase in food consumption in most species. This increase is most apparent during the first 6 postinjection hours, although it may persist as long as 10 hr. There are no published descriptions of alterations in food consumption subsequent to the hyperphagia. In the present study male and female rats were injected with 2DG (750 mg/kg IP), insulin (regular, 20 U/kg SC) or distilled water, and food intake was compared to baseline levels during the next 1,6 and 24 hr. Results showed that food intake: (1) was not affected by injections of water: (2) was higher than normal during all 3 time periods following insulin injections: and (3) was higher than normal at 1 and 6 hr following 2DG, but significantly lower than normal by the end of 24 hr. The reasons underlying the development of hypophagia subsequent to the initial hyperphagia produced by 2DG are presently unknown.

Effects of prior shock and scopolamine on aggressive behavior and blood glucose levels in the rat

The present experiment studied shock-elicited aggression (SEA), interspecific attack, and blood glucose levels, as a function of prior experience with foot shock and scopolamine administration. Prior experience with shock and fighting increased later SEA frequencies, although prior shock experience, without the opportunity to fight had little effect, relative to control animals. Prior shock experience increased mouse attack, but had no effect on frog attack. Scopolamine injections decreased SEA and frog attack, during the first postinjection hour. However, SEA was less affected by scopolamine in animals with prior shock experience. It was also found that prior shock unpaired animals produced larger increases in blood glucose than did prior shock to paired animals. Scopolamine increased blood glucose levels in all animals regardless of shock-fighting history. However, animals with a prior history of foot shock showed greater blood glucose elevations at lower scopolamine dosages than did animals without a prior history of shock. These results suggest that although SEA, and frog and mouse attack may be different models of animal aggression, they have at least some biochemical and experiential determinants in common.

Plasma clearance and renal excretion of erythrocyte cryoprotectant hydroxyethylated amylopectin.

The value of low molecular weight-hydroxyethylated amylopectin (cryo-HES) as an extracellular cryoprotectant has been demonstrated in vitro. It is important that details of the intravascular persistence and urinary excretion be determined to compare with data already available as other grades of HES and with data on transfusion of cryo-HES cryoprotected blood. Following a single 400 ml (14% solution) infusion in man, the intravascular clearance of cryo-HES was well described mathematically by the equation: y = 3.30+6.49e-0.15kappa. The plasma concentration of cryo-HES fell to half its peak value in approximately 9.6 h. Approximately 20% of the total infused cryo-HES was excreted in the urine during the first post-injection hour, and 50% by 72 h. The ESR was not altered significantly by the presence of this material. The present study indicates that cryo-HES is eliminated rapidly and may thus be safe for transfusion to recipients of frozen blood.

L‐DOPA effects on sexual behaviour: An experimental Study

Abstract Following the observation by Benkert (1972), that L‐DOPA influences the sexual behaviour of rats, we studied the L‐DOPA (5.6 mg/kg), I.P. induced sexual behaviour in male Wistar rats (average weight of 350 g), in relation to side‐effects on blood hormone levels and via indirect side‐effects of the sexual partner. A percentage of time spent in sexual behaviour was achieved by counting the number of sexual responses over a post injection hour. A camera set to record 15 slides per minute was placed in the animal behaviour room and thereby eliminated the necessity of distracting human observers. This film record also allowed a more slow and careful analysis by several different researchers at their own time convenience. A record of individual animal behaviour changes with time was also possible. L‐DOPA brought about no definite change in amount of time spent in overall sexual activity, though it may have been responsible for an increase in the amount of time spent in mounting.