1.Clinical effect of propranolol in the treatment of respiratory hemangioma in infants and young children.
Yong-Qi CHEN ; Li-Li ZHONG ; Xiao-Fang DING
Chinese Journal of Contemporary Pediatrics 2020;22(7):785-789
OBJECTIVE:
To study the clinical effect of oral propranolol in the treatment of respiratory hemangioma in infants and young children.
METHODS:
A retrospective analysis was performed from the chart review data of children with respiratory hemangioma treated by oral propranolol and diagnosed by bronchoscopy and laryngeal plain enhanced CT/MRI from November 2012 to December 2019.
RESULTS:
A total of 20 children were enrolled. All children had improvement in the symptoms of laryngeal stridor and dyspnea after oral administration of propranolol for 1-2 days. The median treatment time was 10 months (range 6-12 months). The median follow-up time was 10 months (range 3-15 months). Of the 20 children, 19 (95%) achieved regression of tumor, and 1 (5%) experienced an increase in tumor size during reexamination at 6 months after drug withdrawal and had no recurrence after the treatment with an increased dose of propranolol for 6 months. Only 1 child (5%) had adverse reactions, and 1 child (5%) was still under treatment.
CONCLUSIONS
Oral propranolol can quickly relieve the symptoms such as dyspnea and achieve tumor regression, with few adverse events, and it is therefore an effective method for the treatment of respiratory hemangioma in infants and young children.
Administration, Oral
;
Adrenergic beta-Antagonists
;
Child
;
Child, Preschool
;
Hemangioma
;
Humans
;
Infant
;
Neoplasm Recurrence, Local
;
Propranolol
;
Retrospective Studies
;
Treatment Outcome
2.Pharmacological Therapy of Portal Hypertension: Focused on Korean Data.
The Korean Journal of Gastroenterology 2005;45(6):381-386
Portal hypertension as a consequence of liver cirrhosis is responsible for serious complications such as variceal bleeding, ascites and hepatic encephalopathy. Successful pharmacological treatment of portal hypertension can prevent the risk of the variceal bleeding, and contribute to reduce the morbidity and mortality in patients with liver cirrhosis. To identify the effect of drugs on portal hypertension, portal pressure was evaluated accurately before and after the drug administration. The hepatic venous pressure gradient has been accepted as the gold-standard method for assessing the severity of portal hypertension and the response to drug treatment. The mean hepatic venous pressure gradient was 15.1+/-5.4 mmHg in Korean cirrhotic patients who had experienced variceal bleeding. Non-selective beta blockers are the treatment of choice for primary and secondary prevention of variceal bleeding. The dose of propranolol should be subsequently adjusted until the resting heart rate had been reduced by 25% or less than 55 beats per minute. It has been reported that the optimal dose of propranolol is variable due to racial differences in cardiovascular receptor sensitivity. In Korean patients with portal hypertension and liver cirrhosis, the mean required dose of propranolol to reach target heart rate was 165 mg (range; 80-280 mg). This review covers mainly the results of the pharmacological therapy of portal hypertension in Korean cirrhotic patients.
Adrenergic beta-Antagonists/administration & dosage
;
Hepatic Veins
;
Humans
;
Hypertension, Portal/diagnosis/*drug therapy/physiopathology
;
Korea
;
Liver Cirrhosis/complications/physiopathology
;
Propranolol/administration & dosage
;
Venous Pressure/drug effects
3.Preparation of atenolol monolithic osmotic pump tablets.
Long-Xiao LIU ; Bin-Jie CHE ; Qing XU
Acta Pharmaceutica Sinica 2006;41(5):457-460
AIMThe simplified preparative method and formulation for atenolol monolithic osmotic pump tablets were investigated.
METHODSThe core tablets with an indentation were compressed by the punch with a needle. Osmotic pump tablets were prepared by coating the indented tablets. Similarity factor was used to evaluate formulation of osmotic pump tablets.
RESULTSThe formulation of core tablets and the composition and thickness of coating membrane showed marked effects on drug release. Orifice size of core tablets in the range of 1.00 - 1.14 mm scarcely affected drug release.
CONCLUSIONThe preparation of osmotic pump tablets was simplified with the exempting of laser drilling. The atenolol monolithic osmotic pump tablets could deliver drug constantly for 24 h.
Adrenergic beta-Antagonists ; administration & dosage ; chemistry ; Atenolol ; administration & dosage ; chemistry ; Delayed-Action Preparations ; Drug Carriers ; Osmosis ; Polyethylene Glycols ; chemistry ; Tablets ; Technology, Pharmaceutical ; methods
4.5-HT1A/1B receptors, alpha2-adrenoceptors and the post-receptor adenylate cyclase activation in the mice brain are involved in the antidepressant-like action of agmatine.
Xian-Zhong JIANG ; Yun-Feng LI ; You-Zhi ZHANG ; Hong-Xia CHEN ; Ji LI ; Nai-Ping WANG
Acta Pharmaceutica Sinica 2008;43(5):467-473
This study is to explore the possible mechanisms of the antidepressant-like effect of agmatine. By using two traditional "behavior despair" model, tail suspension test and forced swimming test, we examined the effects of some monoamine receptor antagonists (including beta-adrenergic receptor antagonist propranolol, beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol, alpha2-adrenergic receptor antagonists yohimbine and idazoxan and 5-HT3 receptor antagonist tropisetron) on the antidepressant-like action of agmatine in mice. Activity of adenylate cyclase (AC) in the synapse membrane from rat frontal cortex was determined by radioimmunoassay. Single dose of agmatine (5-40 mg x kg(-1), ig) dose-dependently decrease the immobility time in tail suspension test in mice, indicating an antidepressant-like effect. The effect of agmatine (40 mg x kg(-1), ig) was antagonized by co-administration of beta-adrenergic receptor antagonist/5-HT1A/1B receptor antagonist pindolol (20 mg x kg(-1), ip), alpha2-adrenergic receptor antagonists yohimbine (5-10 mg x kg(-1), ip) or idazoxan (4 mg x kg(-1), ip), but not beta-adrenergic receptor antagonist propranolol (5-20 mg x kg(-1), ip) and 5-HT3 receptor antagonist tropisetron (5-40 mg x kg(-1), ip). Agmatine (5-40 mg x kg(-1), ig) also dose-dependently decrease the immobility time in forced swimming test in mice. The effect of agmatine (40 mg x kg(-1), ig) was also antagonized by pindolol (20 mg x kg(-1), ip), yohimbine (5-10 mg x kg(-1), ip), or idazoxan (4 mg x kg(-1), ip). Incubation of agmatine (0.1-6.4 micromol x L(-1)) with the synaptic membrane extracted from rat frontal cortex activated the AC in a dose-dependent manner in vitro. While the effect of agmatine (6.4 micromol x L(-1)) was dose-dependently antagonized by pindolol (1 micromol x L(-1)) or yohimbine (0.25-1 micromol x L(-1)). Chronic treatment with agmatine (10 mg x kg(-1), ig, bid, 2 w) or fluoxetine (10 mg x kg(-1), ig, bid, 2 w) increased the basic activity, as well as the Gpp (NH)p (1-100 micromol x L(-1)) stimulated AC activity in rat prefrontal cortex. These results indicate that regulation on 5-HT1A/1B and alpha2 receptors, and activation AC in the frontal cortex is one of the important mechanisms involving in agmatine's antidepressant-like action.
Adenylyl Cyclases
;
metabolism
;
Adrenergic alpha-Antagonists
;
pharmacology
;
Adrenergic beta-Antagonists
;
pharmacology
;
Agmatine
;
administration & dosage
;
pharmacology
;
Animals
;
Antidepressive Agents
;
administration & dosage
;
pharmacology
;
Behavior, Animal
;
drug effects
;
Depression
;
metabolism
;
physiopathology
;
Dose-Response Relationship, Drug
;
Fenclonine
;
pharmacology
;
Idazoxan
;
pharmacology
;
Male
;
Mice
;
Pindolol
;
pharmacology
;
Random Allocation
;
Rats
;
Rats, Wistar
;
Receptors, Biogenic Amine
;
antagonists & inhibitors
;
Serotonin 5-HT1 Receptor Antagonists
;
Swimming
;
Synapses
;
enzymology
;
Yohimbine
;
pharmacology
5.A clinical study of Timolol Maleate Eye Drops for the treatment of superficial infantile hemangiomas.
Yu LINJUN ; Xu JIACHUAN ; Su BAOLI ; Xiong QIXING ; Luo CHUNFEN
Chinese Journal of Plastic Surgery 2015;31(6):440-445
OBJECTIVETo dicuss the clinical efficacy of Timolol Maleate Eye Drops in the treatment of superficial infantile hemangiomas. Methods From April 2012 to May 2014, 210 patients with superficial infantile hemangiomas were included. According to the parents' choice, a total of 176 cases were treated with Timolol Maleate Eye Drops as the treatment group, and the 34 cases who received the treatment of "wait and see" was included in the control group. In the treatment group, the gauzes were dipped into the eye drops and putted evenly on the surface of the hemangioma, 3-4 times daily and lasted for more than 20 minutes. The gauze should completely cover the surface of the tumor. The follow-up periods were 3 weeks and 6 months after treatment with the pictures to record the treatment effect. The therapeutic effect was graded as: grade I (unable to control the growth of the hemangioma), II (the growth of the hemangioma stagnated), III (hemangioma significantly subsided), IV (the hemangioma completely disappeared). The effective rate included the cases with grade II and above grade II . The cure cases included the cases with grade IV. The data was analyzed with the statistical software SPSS 17.0 and the Chi-square test (P < 0.05).
RESULTS3 cases in the treatment group showed eczema action. Tumor ulcer happened in 1 case in treatment group. The side effect rate was 2.3% . The results at 3 weeks following in the treatment group showed that the growth of the hemangioma were stagnated in 154 cases. The color of hemangioma became darker in different degrees than before, and the texture of the hemangioma became soft in majority of children, and the thickness of hemangioma became thinner in some cases. However, only 4 cases showed the hemangiomas were subsided, 18 cases showed the color of the part of the hemangiomas were brighter than before, and 12 cases of the hemangiomas remained original state in the control group. The results of 6 weeks following the treatment showed that 18 patients in the treatment group reached the standard of the grade IV, 84 patients reached the standard of the grade III, 60 patients achieved in the standard of grade II, and only 14 patients showed the volume of hemangiomas were increased as grade I. The effective rate was 58. 0% , and the cure rate was 10. 2% in treatment group. In control group, no children reached the standard of the grade IV, 4 cases reached the standard of grade III, 13 cases who remained original state reached the standard of grade II, and 17 cases showed the volume of hemangiomas continued to increase as grade I . The effective rate was 11. 8% , and the cure rate was 0. By comparison, the effective rate and the cure rate in the control group were relatively lower than those in the treatment group (P < 0.05).
CONCLUSIONSThe efficacy of Timolol Maleate Eye Drops in the treatment of superficial infantile hemangioma is exact, especially in the proliferative phase of the infantile hemangioma. It is safe and easy to perform with mild side effect. It should be selected as first-line treatment.
Administration, Topical ; Adrenergic beta-Antagonists ; administration & dosage ; Child ; Hemangioma ; drug therapy ; Humans ; Ophthalmic Solutions ; administration & dosage ; Skin Neoplasms ; drug therapy ; Timolol ; administration & dosage ; adverse effects ; Treatment Outcome ; Watchful Waiting
6.Treatment of infantile parotid hemangioma with propranolol.
Xue-jian LIU ; Zhong-ping QIN ; Mao-zhong TAI ; Ke-lei LI ; Chun-xiao GE
Chinese Journal of Stomatology 2010;45(5):292-294
OBJECTIVETo evaluate the short-term results and safety of propranolol for the treatment of infantile parotid hemangioma.
METHODSOral propranolol was administered to 17 infants with parotid hemangioma at a dose of 1.0-1.5 mg per kilogram of body weight per day. The patients were revisited once a week. The changes of the tumor size, texture and colour were monitored and recorded at a regular interval. The adverse effects after medication were observed and managed accordingly. The short-term results were evaluated using a 4 scales system.
RESULTSAmong the 17 patients treated, the follow-up time was 5 to 10 months. The overall response was scale I in 0 patient, scale II in 0 patients, scale III in 5 patients, and scale IV in 12 patients. No serious adverse effects were encountered.
CONCLUSIONSOral propranolol at a lower dose is a safe and effective method for the treatment of infantile parotid hemangioma. The short-term results were excellent and the side effects minimal.
Administration, Oral ; Adrenergic beta-Antagonists ; administration & dosage ; therapeutic use ; Female ; Follow-Up Studies ; Hemangioma ; drug therapy ; Humans ; Infant ; Male ; Parotid Neoplasms ; drug therapy ; Propranolol ; administration & dosage ; therapeutic use ; Treatment Outcome
7.Prevention of Hypokalemia by Oral Propranolol before Induction of Anesthesia.
Young Kyoo CHOI ; Jae Won CHOI ; Keon Sik KIM ; Dong Ok KIM ; Wha Ja KANG ; Ok Young SHIN ; Dong Soo KIM ; Doo Ik LEE
Korean Journal of Anesthesiology 1993;26(1):28-35
To determine the role of catecholamines in regulation of potassium homeostasis, we measured the serum potassium level of 60 healthy subjects on admission and just before the induction of anesthesia, with or without propranolol administration. Catecholamine-induced hypokalemia is developed by beta-2 receptor stimulation, not mediated by insulin, renin, or aldosterone. The activation of beta-2 adrenoreceptors causes a dose-dependent decrease in plasma potassium, probably by shifting potassium into the cell. By this mechanism, epinephrine may cause hypokalemia and leads to cardiac arrhythmias. These preventive mechanism of hypokalemia may contribute to the cardioprotective action of non-selective beta adrenergic blockers. In each patient, serum potassium was measured on admission and just before induction, and a ECG was analyzed prior to surgery and lead II monitoring continued during anesthesia. Mean arterial pressure and heart rate were measured on admission, preinduction, preintubation, and preoperation. Sixty patients divided into two groups. In group I (n=30), placebo was given; Group II (n=30), 40 mg of propranolol was given orally three hours prior to the induction of anesthesia. The results are as followed; 1) Comparing the preinduction potassium level with that measured two days before operation, 33% of the control group were normokalemic(> or =3.6mEq/L), 57% hypokalemic(3.1-3.5 mEq/ L), and 10% severe hypokalemic(< or =3.0 mEq/L). In the group pretreated with propranolol, 90 were normokalemic, and 10% hypokalemic. 2) Mean serum potassium level on admission and just before induction were 3.94+/-0.31 mEq/L and 3.40+/-0.38 mEq/L, respectively, in control group; 3.99+/-0,46 mEq/L and 4.16+/-0.05 mEq/L in propranolol administered group, indicating a significant increase(P< 0.01). 3) After propranolol administration, mean arterial pressure decreased significantly before operation (P<0.05), and heart rate also decreased significantly before endotracheal intubation (P< 0.01) and before operation (P< 0.05) compared with control group. 4) No arrhythmia occurred at any time in both group of patients who noted to be hypokalemic priorly. This study suggests that the oral administration of 40 mg of propranolol may prevent hypokalemia and attenuate the rate of increase in blood pressure and heart rate after induction of anesthesia. But further studies may be necessary for more detailed mechanism in preventing hypokalemia and hemodynamic evaluations regarding propranolol.
Administration, Oral
;
Adrenergic beta-Antagonists
;
Aldosterone
;
Anesthesia*
;
Arrhythmias, Cardiac
;
Arterial Pressure
;
Blood Pressure
;
Catecholamines
;
Electrocardiography
;
Epinephrine
;
Heart Rate
;
Hemodynamics
;
Homeostasis
;
Humans
;
Hypokalemia*
;
Insulin
;
Intubation, Intratracheal
;
Ions
;
Plasma
;
Potassium
;
Propranolol*
;
Renin
8.Prevention of Hypokalemia by Oral Propranolol before Induction of Anesthesia.
Young Kyoo CHOI ; Jae Won CHOI ; Keon Sik KIM ; Dong Ok KIM ; Wha Ja KANG ; Ok Young SHIN ; Dong Soo KIM ; Doo Ik LEE
Korean Journal of Anesthesiology 1993;26(1):28-35
To determine the role of catecholamines in regulation of potassium homeostasis, we measured the serum potassium level of 60 healthy subjects on admission and just before the induction of anesthesia, with or without propranolol administration. Catecholamine-induced hypokalemia is developed by beta-2 receptor stimulation, not mediated by insulin, renin, or aldosterone. The activation of beta-2 adrenoreceptors causes a dose-dependent decrease in plasma potassium, probably by shifting potassium into the cell. By this mechanism, epinephrine may cause hypokalemia and leads to cardiac arrhythmias. These preventive mechanism of hypokalemia may contribute to the cardioprotective action of non-selective beta adrenergic blockers. In each patient, serum potassium was measured on admission and just before induction, and a ECG was analyzed prior to surgery and lead II monitoring continued during anesthesia. Mean arterial pressure and heart rate were measured on admission, preinduction, preintubation, and preoperation. Sixty patients divided into two groups. In group I (n=30), placebo was given; Group II (n=30), 40 mg of propranolol was given orally three hours prior to the induction of anesthesia. The results are as followed; 1) Comparing the preinduction potassium level with that measured two days before operation, 33% of the control group were normokalemic(> or =3.6mEq/L), 57% hypokalemic(3.1-3.5 mEq/ L), and 10% severe hypokalemic(< or =3.0 mEq/L). In the group pretreated with propranolol, 90 were normokalemic, and 10% hypokalemic. 2) Mean serum potassium level on admission and just before induction were 3.94+/-0.31 mEq/L and 3.40+/-0.38 mEq/L, respectively, in control group; 3.99+/-0,46 mEq/L and 4.16+/-0.05 mEq/L in propranolol administered group, indicating a significant increase(P< 0.01). 3) After propranolol administration, mean arterial pressure decreased significantly before operation (P<0.05), and heart rate also decreased significantly before endotracheal intubation (P< 0.01) and before operation (P< 0.05) compared with control group. 4) No arrhythmia occurred at any time in both group of patients who noted to be hypokalemic priorly. This study suggests that the oral administration of 40 mg of propranolol may prevent hypokalemia and attenuate the rate of increase in blood pressure and heart rate after induction of anesthesia. But further studies may be necessary for more detailed mechanism in preventing hypokalemia and hemodynamic evaluations regarding propranolol.
Administration, Oral
;
Adrenergic beta-Antagonists
;
Aldosterone
;
Anesthesia*
;
Arrhythmias, Cardiac
;
Arterial Pressure
;
Blood Pressure
;
Catecholamines
;
Electrocardiography
;
Epinephrine
;
Heart Rate
;
Hemodynamics
;
Homeostasis
;
Humans
;
Hypokalemia*
;
Insulin
;
Intubation, Intratracheal
;
Ions
;
Plasma
;
Potassium
;
Propranolol*
;
Renin
9.Role of Soluble ST2 Levels and Beta-Blockers Dosage on Cardiovascular Events of Patients with Unselected ST-Segment Elevation Myocardial Infarction.
Wei-Ping HUANG ; Xuan ZHENG ; Lei HE ; Xi SU ; Cheng-Wei LIU ; Ming-Xiang WU
Chinese Medical Journal 2018;131(11):1282-1288
BackgroundSerum soluble ST2 (sST2) levels are elevated early after acute myocardial infarction and are related to adverse left ventricular (LV) remodeling and cardiovascular outcomes in ST-segment elevation myocardial infarction (STEMI). Beta-blockers (BB) have been shown to improve LV remodeling and survival. However, the relationship between sST2, final therapeutic BB dose, and cardiovascular outcomes in STEMI patients remains unknown.
MethodsA total of 186 STEMI patients were enrolled at the Wuhan Asia Heart Hospital between January 2015 and June 2015. All patients received standard treatment and were followed up for 1 year. Serum sST2 was measured at baseline. Patients were divided into four groups according to their baseline sST2 values (high >56 ng/ml vs. low ≤56 ng/ml) and final therapeutic BB dose (high ≥47.5 mg/d vs. low <47.5 mg/d). Cox regression analyses were performed to determine whether sST2 and BB were independent risk factors for cardiovascular events in STEMI.
ResultsBaseline sST2 levels were positively correlated with heart rate (r = 0.327, P = 0.002), Killip class (r = 0.408, P = 0.000), lg N-terminal prohormone B-type natriuretic peptide (r = 0.467, P = 0.000), lg troponin I (r = 0.331, P = 0.000), and lg C-reactive protein (r = 0.307, P = 0.000) and negatively correlated to systolic blood pressure (r = -0.243, P = 0.009) and LV ejection fraction (r = -0.402, P = 0.000). Patients with higher baseline sST2 concentrations who were not titrated to high-dose BB therapy (P < 0.0001) had worse outcomes. Baseline high sST2 (hazard ratio [HR]: 2.653; 95% confidence interval [CI]: 1.201-8.929; P = 0.041) and final low BB dosage (HR: 1.904; 95% CI, 1.084-3.053; P = 0.035) were independent predictors of cardiovascular events in STEMI.
ConclusionsHigh baseline sST2 levels and final low BB dosage predicted cardiovascular events in STEMI. Hence, sST2 may be a useful biomarker in cardiac pathophysiology.
Adrenergic beta-Antagonists ; administration & dosage ; therapeutic use ; Adult ; Aged ; Biomarkers ; blood ; Female ; Humans ; Interleukin-1 Receptor-Like 1 Protein ; blood ; Male ; Middle Aged ; Prognosis ; Prospective Studies ; ST Elevation Myocardial Infarction ; blood ; drug therapy ; pathology
10.Antiarrhythmic effect of TJ0711.
Xiao-Jing ZHANG ; Jun QIU ; Gao LI
Acta Pharmaceutica Sinica 2014;49(3):419-426
To study the antiarrhythmic effect of the newly developed alpha/beta-blocker TJ0711, a variety of animal models of arrhythmia were induced by CaCl2, ouabain and ischemia/reperfusion. Glass microelectrode technique was used to observe action potentials of right ventricular papillary muscle of guinea pig. The onset time of arrhythmia induced by CaCl2 was significantly prolonged by TJ0711 at 0.75, 1.5 and 3 mg x kg(-1) doses. TJ0711 (1.5 and 3 mg x kg(-1)) can significantly shorten the ventricular tachycardia (VT) and ventricular fibrillation (VF) duration, the incidence of VF and mortality were significantly reduced. On ischemia-reperfusion-induced arrhythmic model, TJ0711 (0.25, 0.5, 1 and 2 mg x kg(-1)) can significantly reduce the ventricular premature contraction (PVC), VT, VF incidence, mortality, arrhythmia score with a dose-dependent manner. At the same time, rats serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities decreased significantly by TJ0711 (1 and 2 mg x kg(-1)). Ouabain could cause arrhythmia in guinea pigs, when TJ0711 (0.375, 0.75, 1.5 and 3 mg x kg(-1)) was given, the doses of ouabain inducing a variety of arrhythmia PVC, VT, VF, cardiac arrest (CA) were significantly increased with a dose-dependent manner. In the TJ0711 0.1-30 micromol x L(-1) concentration range, guinea pig right ventricular papillary muscle action potential RP (rest potential), APA (action potential amplitude) and V(max) (maximum velocity of depolarization) were not significantly affected. APD20, APD50 and APD90 had a shortening trend but no statistical difference with the increase of TJ0711 concentration. TJ0711 has antiarrhythmic effect on the sympathetic nerve excitement and myocardial cell high calcium animal arrhythmia model. Myocardial action potential zero phase conduction velocity and resting membrane potential were not inhibited by TJ0711. APD20, APD50 and APD90 were shortened by TJ0711 at high concentration. Its antiarrhythmic action mechanism may be besides the action of blocking beta1 receptor, may also have a strong selective blocking action on alpha1 receptor and reducing intracellular calcium concentration.
Action Potentials
;
drug effects
;
Adrenergic alpha-Antagonists
;
administration & dosage
;
pharmacology
;
Adrenergic beta-Antagonists
;
administration & dosage
;
pharmacology
;
Animals
;
Anti-Arrhythmia Agents
;
administration & dosage
;
pharmacology
;
Arrhythmias, Cardiac
;
blood
;
chemically induced
;
etiology
;
pathology
;
physiopathology
;
Calcium Chloride
;
Creatine Kinase
;
blood
;
Dose-Response Relationship, Drug
;
Female
;
Guinea Pigs
;
Heart Ventricles
;
cytology
;
Lactate Dehydrogenases
;
blood
;
Male
;
Myocardial Reperfusion Injury
;
complications
;
Myocytes, Cardiac
;
drug effects
;
physiology
;
Ouabain
;
Papillary Muscles
;
cytology
;
Phenoxypropanolamines
;
administration & dosage
;
pharmacology
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley