scholarly journals Duration of Mydriasis Produced by 0.5% and 1% Tropicamide in Sprague–Dawley Rats

Author(s):  
Stephanie A Pumphrey ◽  
Yoonjin Moon ◽  
Jenelle M Francis ◽  
Misty J Williams-Fritze ◽  
David Lee-Parritz

Ophthalmic examination (OE) is a common part of preclinical studies. Pupillary dilation to facilitate OE may affect results of other planned testing. The purpose of this study was to determine the duration of mydriasis produced by commercially available 0.5% and 1% tropicamide in ophthalmologically normal albino rats. Twelve female Sprague–Dawley rats were used. A single drop of 1% tropicamide was applied to one eye of each rat. A single drop of balanced salt solution (BSS) was applied to the contralateral eye. Measurements of pupillary diameter (PD) were obtained using a digital caliper at 0, 20, 40, 60, 120, 180, 240, 300, and 360 min after application. After a 3-wk washout period, the procedure was repeated using 0.5% tropicamide. Pupillary dilation sufficient to allow posterior segment evaluation was achieved with 0.5% and 1% tropicamide. Maximum PD after treatment with 0.5% tropicamide was 4.17 ± 0.22 mm at 40 min; maximum PD after treatment with 1% tropicamide was not significantly different (4.28 mm at both 20 and 40 min (± 0.43 mm and 0.23 mm, respectively)). Mean PD remained above 3.5 mm in treated eyes for 60 min. In eyes treated with 0.5% tropicamide, mean PD was significantly different from baseline mean PD for that eye up to 300 min. In eyes treated with 1% tropicamide, mean PD was significantly different thanbaseline mean PD for that eye at all timepoints. Both concentrations of tropicamide produced a transient mild to moderate mydriasis in the contralateral eye. Duration of action is at least 5 h for 0.5% tropicamide and 6 h for 1% tropicamide. Results of this study support use of 0.5% tropicamide for OE in albino rats, with administration performed no more than 60 min prior to examination.

1994 ◽  
Vol 79 (1) ◽  
pp. 211-215 ◽  
Author(s):  
William F. Vitulli ◽  
Rwanda Aker ◽  
Stanley W. Howard ◽  
Wendy M. Jones ◽  
Morgan W. Kimball ◽  
...  

Salt (sodium chloride) has been linked to increased blood pressure and a rise in core body temperature. The objective of this study was to investigate the role played by salt in altering behavioral thermoregulation in albino rats. Different doses of sodium chloride were administered (ip) prior to fixed-interval 2-min. schedules of microwave reinforcement in rats tested in a cold Skinner Box. Three Sprague-Dawley rats were conditioned to regulate their thermal environment with 5-sec. exposures of MW reinforcement in a repeated-measures reversal design. Friedman's non-parametric test showed significant differences among sodium chloride doses and physiologically normal saline. Post hoc sign tests showed that all doses of NaCI suppressed operant behavior for heat except 60 mg/kg. The hypothesis that sodium chloride lowers hypothalamic set point for heat was partially supported.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Susan D’Souza ◽  
Jabar A. Faraj ◽  
Stefano Giovagnoli ◽  
Patrick P. DeLuca

The aim of this study was to design and evaluate biodegradable PLGA microspheres for sustained delivery of Risperidone, with an eventual goal of avoiding combination therapy for the treatment of schizophrenia. Two PLGA copolymers (50 : 50 and 75 : 25) were used to prepare four microsphere formulations of Risperidone. The microspheres were characterized by several in vitro techniques. In vivo studies in male Sprague-Dawley rats at 20 and 40 mg/kg doses revealed that all formulations exhibited an initial burst followed by sustained release of the active moiety. Additionally, formulations prepared with 50 : 50 PLGA had a shorter duration of action and lower cumulative AUC levels than the 75 : 25 PLGA microspheres. A simulation of multiple dosing at weekly or 15-day regimen revealed pulsatile behavior for all formulations with steady state being achieved by the second dose. Overall, the clinical use of Formulations A, B, C, or D will eliminate the need for combination oral therapy and reduce time to achieve steady state, with a smaller washout period upon cessation of therapy. Results of this study prove the suitability of using PLGA copolymers of varying composition and molecular weight to develop sustained release formulations that can tailor in vivo behavior and enhance pharmacological effectiveness of the drug.


2019 ◽  
Vol 19 (1) ◽  
pp. 193-206 ◽  
Author(s):  
Shinichi Kokubu ◽  
Kelly A. Eddinger ◽  
Thi M.-D. Nguyen ◽  
Lena Libertad Huerta-Esquivel ◽  
Shigeki Yamaguchi ◽  
...  

Abstract Background and aims We systematically characterized the potency and side effect profile of a series of small opioid peptides with high affinity for the mu opioid receptor. Methods Male Sprague Dawley rats were prepared with intrathecal (IT) catheters, assessed with hind paw thermal escape and evaluated for side effects including Straub tail, truncal rigidity, and pinnae and corneal reflexes. In these studies, DMT-DALDA (dDAL) (H-Dmt-D-Arg-Phe-Lys-NH2 MW=981), dDALc (H-Dmt-Cit-Phe-Lys-NH2 MW=868), dDALcn (H-Dmt-D-Cit-Phe-Nle-NH2 MW=739), TAPP (H-Tyr-D-Ala-Phe-Phe-NH2 MW=659), dDAL-TICP ([Dmt1]DALDA-(CH2)2-NH-TICP[psi]; MW=1519), and dDAL-TIPP (H-Dmt-D-Arg-Phe-Lys(Nε-TIPP)-NH2 were examined. In separate studies, the effects of approximately equiactive doses of IT DMT DALDA (10 pmol), morphine (30 nmol) and fentanyl (1 nmol) were examined on formalin-induced flinching at different pretreatment intervals (15 min – 24 h). Results (1) All agents resulted in a dose-dependent reversible effect upon motor function (Straub Tail>Truncal rigidity). (2) The ordering of analgesic activity (%MPE) at the highest dose lacking reliable motor signs after bolus delivery was: DMT-DALDA (80%±6/3 pmol); dDALc (75%±8/1 pmol); dDALcn (84%±10/300 pmol); TAPP (56%±12/10 nmol); dDAL-TICP (52%±27/300 pmol). (3) All analgesic effects were reversed by systemic (IP) naloxone (1 mg/kg). Naltrindole (3 mg/kg, IP) had no significant effect upon the maximum usable peptide dose. (4) Tolerance and cross-tolerance development after 5 daily boluses of DMT-DALDA (3 pmol) and morphine (30 nmol) revealed that both agents displayed a progressive decline over 5 days. (5) Cross-tolerance assessed at day 5 revealed a reduction in response to morphine in DMT-DALDA treated animal but not DMT-DALDA in the morphine treated animal, indicating an asymmetric cross-tolerance. (6) IT DMT-DALDA, morphine and fentanyl resulted in significant reductions in phase 1 and phase 2 flinching. With a 15 min pretreatment all drugs resulted in comparable reductions in flinching. However, at 6 h, the reduction in flinching after DMT-DALDA and morphine were comparably reduced while fentanyl was not different from vehicle. All effects on flinching were lost by 24 h. Conclusions These results emphasize the potent mu agonist properties of the DALDA peptidic structure series, their persistence similar to morphine and their propensity to produce tolerance. The asymmetric cross-tolerance between equiactive doses may reflect the relative intrinsic activity of morphine and DMT-DALDA. Implications These results suggest that the DALDA peptides with their potency and duration of action after intrathecal delivery suggest their potential utility for their further development as a spinal therapeutic to manage pain.


1996 ◽  
Vol 83 (1) ◽  
pp. 15-20 ◽  
Author(s):  
William F. Vitulli ◽  
Janet E. McAleer ◽  
Andrea C. Rockwell ◽  
Charles R. Granade ◽  
Deborah L. Parman ◽  
...  

Aspartame (L-aspartyl-L-phenylalanine methyl ester) was administered intraperitoneally to 9 Sprague-Dawley rats partitioned into 2 studies (4 in Study 1 and 5 for a replication in Study 2) over a two-year period using a within-subjects, repeated-measures reversal design Behavioral thermoregulation was assessed in a cold Skinner Box using 5-sec. exposures of microwave radiation [Specific Absorption Rate = 0.34 Watts/kg/(mW/cm2)] as reinforcing stimuli under a fixed-interval 2-min. schedule of positive reinforcement. Two factorial analyses of variance [5 (doses) × 8 (hours)] indicated that the main effect for the doses of aspartame (2, 4, 8, 16 mg/kg, and saline control) was not significant; yet, the interaction (dose × hours) was significant (p<.05). Tentatively, aspartame should not cause an uncomfortable rise in body temperature (as sugar can do) when consumed in common substances such as soft drinks, yogurt, tea, coffee, etc., in doses commensurate with “hedonic” sweetness.


1974 ◽  
Vol 11 (2) ◽  
pp. 144-152 ◽  
Author(s):  
J. E. Gray ◽  
R. N. Weaver ◽  
N. D. Connor

The kidneys of 39 wild Norway rats ( Rattus noryegicus), 9 months or older, were examined for evidence of chronic progressive nephrosis, which commonly affects year-old albino rats. An infectious process resembling pyelonephritis was found in two rats. Protein absorption droplets, intranuclear inclusion bodies resembling those of lead intoxication, and large ‘aberrant’ nuclei were seen in the epithelial cells of the proximal convolutions. The nematode, Trichosomoides crassicauda, was found in the renal pelvis of approximately one fourth of the rats. Basement membranes of the glomerular tufts, Bowman's capsule and proximal tubule were examined in four rats by electron microscopy. The mean thickness of basement membranes of peripheral glomerular loops was 0.28 ± 0.09 μm, which is comparable to that of young healthy Sprague-Dawley rats. The protein content in 65 determinations of 24-hour serial collections of urine ranged from less than 1 to 3.9 mg/ml. No tendency was observed toward increased protein excretion or progressive deterioration of the kidneys, such as occurs in older Sprague-Dawley rats.


2013 ◽  
Vol 58 (No. 11) ◽  
pp. 520-524 ◽  
Author(s):  
S.O. Ekere ◽  
C.N. Okoye ◽  
A.F. Udoumoh

The effects of methanolic extract of Dracaena arborea on mean testicular weight, mean cauda epididymal sperm reserve, and testicular morphology were evaluated. A total of sixty mature male Sprague Dawley rats were divided into three equal groups. The first group (A) received distilled water while the other two groups (B and C) received orally the methanolic leaf extracts of Dracaena arborea in two doses (100&nbsp;and 500 mg/kg, respectively) daily for 84 days. Following oral administration of the extract, mean testicular weight, mean cauda epididymal sperm reserve, and testicular morphology were determined on days 28, 42, 56, 70, and 84. The extract produced a significant and dose-dependent increase (P &lt; 0.05) in the sperm number. There was also a significant increase (P &lt; 0.05) in the mean testicular weights on days 70 and 84 of the extract administration. The testicular morphology remained unchanged while further testicular histology examination revealed increased spermatogenesis. It was concluded that the methanolic leaf extract of D. arborea has fertility enhancing properties. &nbsp;


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

Investigation of the spontaneous pituitary adenomas in rat have been limited mainly to light microscopic study. Furth et al. (1973) described them as chromophobic, secreting prolactin. Kovacs et al. (1977) in an ul trastructural investigation of adenomas of old female Long-Evans rats, found that they were composed of prolactin cells. Berkvens et al. (1980) using immunocytochemistry at the light microscopic level, demonstrated that some spontaneous tumors of old Wistar rats could contain GH, TSH or ACTH as well as PRL.


Author(s):  
F. G. Zaki ◽  
E. Detzi ◽  
C. H. Keysser

This study represents the first in a series of investigations carried out to elucidate the mechanism(s) of early hepatocellular damage induced by drugs and other related compounds. During screening tests of CNS-active compounds in rats, it has been found that daily oral administration of one of these compounds at a dose level of 40 mg. per kg. of body weight induced diffuse massive hepatic necrosis within 7 weeks in Charles River Sprague Dawley rats of both sexes. Partial hepatectomy enhanced the development of this peculiar type of necrosis (3 weeks instead of 7) while treatment with phenobarbital prior to the administration of the drug delayed the appearance of necrosis but did not reduce its severity.Electron microscopic studies revealed that early development of this liver injury (2 days after the administration of the drug) appeared in the form of small dark osmiophilic vesicles located around the bile canaliculi of all hepatocytes (Fig. 1). These structures differed from the regular microbodies or the pericanalicular multivesicular bodies. They first appeared regularly rounded with electron dense matrix bound with a single membrane. After one week on the drug, these vesicles appeared vacuolated and resembled autophagosomes which soon developed whorls of concentric lamellae or cisterns characteristic of lysosomes (Fig. 2). These lysosomes were found, later on, scattered all over the hepatocytes.


Author(s):  
D. J. McComb ◽  
J. Beri ◽  
F. Zak ◽  
K. Kovacs

Gonadotroph cell adenomas of the pituitary are infrequent in human patients and are not invariably associated with altered gonadal function. To date, no animal model of this tumor type exists. Herein, we describe spontaneous gonadotroph cell adenomas in old male and female Sprague-Dawley rats by histology, immunocytology and electron microscopy.The material consisted of the pituitaries of 27 male and 38 female Sprague Dawley rats, all 26 months of age or older, removed at routine autopsy. Sections of formal in-fixed, paraffin-embedded tissue were stained with hematoxylin-phloxine-saffron (HPS), the PAS method and the Gordon-Sweet technique for the demonstration of reticulin fibers. For immunostaining, sections were exposed to anti-rat β-LH, anti-ratβ-TSH, anti-rat PRL, anti-rat GH and anti-rat ACTH 1-39. For electron microscopy, tissue was fixed in 2.5% glutaraldehyde, postfixed in 1% OsO4 and embedded in epoxy-resin. Tissue fixed in 10% formalin, embedded in epoxy resin without osmification, was used for immunoelectron microscopy.


Author(s):  
Russell N. A. Cecil ◽  
H. Clarke Anderson

Unfixed proximal tibial epiphyseal growth plates were studied by freeze-etch to confirm the presence of extracellular calcifying matrix vesicles and to determine the substructure of matrix vesicle membranes as compared to plasma and other membranes of intact chondrocytes. Growth plates from 6-10 week old Sprague-Dawley rats were cut into 1x3 mm blocks whose long dimension was oriented either perpendicular or parallel to the long axis of the tibia. Some blocks were fixed at pH 7. 0 in 0. 2M cacodylate - buffered 2. 5% glutaraldehyde for 1 hour at 4ÅC. The blocks were immersed in 30% glycerol solution at 4ÅC for 1 hour, frozen in liquid nitrogen, and then fractured, etched for 2 minutes, and coated with platinum, carbon and 0. 2% Formvar solution. The replicas were cleaned with chromic acid, floated onto Formvar coated grids, and examined with a Phillips EM 300 electron microscope.Fixed and unfixed specimens appeared similar in ultrastructure. Chondrocytes, matrix, and matrix vesicles were identified. In specimens fractured parallel to the long axis of the tibia, the reserve, proliferative, hypertrophic, and calcifying zones could be discerned as described by light and electron microscopy.


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