scholarly journals Solifenacin/Mirabegron Induces an Acute Compliance Increase in the Filling Phase of the Capacity-Reduced Urinary Bladder: A Pressure-Volume Analysis in Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Hsien-Yu Peng ◽  
Cheng-Yuan Lai ◽  
Ming-Chun Hsieh ◽  
Tzer-Bin Lin
Keyword(s):  
Dependent Manner ◽  
Sprague Dawley ◽  
Volume Analysis ◽  
Sprague Dawley Rats ◽  
Bladder Compliance ◽  
Data Points ◽  
Filling Phase ◽  
Acute Increase ◽  
Urine Storage ◽  
Mean Compliance

Aims: Pressure in the bladder, which is a high compliance organ, is only slightly elevated to a considerable filling volume during storage. Although cystometry off-line offers mean compliance, no protocol is available for real-time assays of the dynamics of bladder compliance, and the potential impact of solifenacin and mirabegron on dynamic bladder compliance has not been established.Methods: Along with constantly infused cystometry, a pressure-volume analysis (PVA) was performed by plotting intra-vesical volume against pressure in Sprague-Dawley rats. The instant compliance was assayed as the slope of the trajectory, and the mean compliance (Cm) was determined by the slope of the line produced by regression of the data points at the end of the first, second, and third quarters of the filling phase.Results: Under a steady-state, the PVA trajectory moved clockwise which shaped coincident enclosed loops with stable compliance. Though administering to naïve animals solifenacin, but not mirabegron (both 1 × 10−5−1 × 10−1 mg/kg, i.a.) decreased the peak pressure, both of these reagents exhibited acute increments in the trajectory slope and Cm of the filling phase in a dose-dependent manner (ED50 = 1.4 × 10−4 and 2.2 × 10−5 mg/kg, respectively). Resembling urine frequency/urgency in OAB patients, the voiding frequency of a capacity-reduced bladder was increased in association with decreased compliance which was ameliorated by both acute solifenacin and mirabegron injections (both 1 × 10−1 mg/kg).Conclusion: In addition to their well-known anti-inotropic/relaxative effects, solifenacin, and mirabegron induce an acute increase in bladder compliance to ameliorate OAB-like syndromes. Together with time-domain cystometry, PVA offers a platform for investigating the physiology/pathophysiology/pharmacology of bladder compliance which is crucial for urine storage.

Influence of Slice Thickness and Culture Conditions on the Metabolism of 7-Ethoxycoumarin in Precision-cut Rat Liver Slices

1998 ◽  
Vol 26 (4) ◽  
pp. 541-548
Author(s):  
Roger J. Price ◽  
Anthony B. Renwick ◽  
Paula T. Barton ◽  
J. Brian Houston ◽  
Brian G. Lake
Keyword(s):  
Gas Phase ◽  
Rat Liver ◽  
Xenobiotic Metabolism ◽  
Culture Conditions ◽  
Slice Thickness ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Liver Slices ◽  
Sprague Dawley Rats ◽  
Rat Livers

This study investigated the effects of some experimental variables on the rate of xenobiotic metabolism in precision-cut rat liver slices. Liver slices of 123 ± 8μm (mean ± SEM of six slices), 165 ± 3μm, 238 ± 6μm and 515 ± 14μm thickness were prepared from male Sprague-Dawley rats, and incubated in RPMI 1640 medium in an atmosphere of 95% O2/5% CO2 by using a dynamic organ culture system. Liver slices of all thicknesses metabolised 10μM 7-ethoxycoumarin to total (free and conjugated) 7-hydroxycoumarin in a time-dependent manner. The rate of 7-ethoxycoumarin metabolism was greatest in 165μm thick slices and slowest in 515μm thick slices, being 2.74 ± 0.19pmol/minute/mg slice protein and 0.69 ± 0.07pmol/minute/mg slice protein, respectively. No marked effects on the rate of 7-ethoxycoumarin metabolism in liver slices were observed either by changing the medium to Earle's balanced salt solution (EBSS) or by changing the gas phase to 95% air/5% CO2. Moreover, the perfusion of rat livers with EBSS at 2–4°C, prior to preparation of tissue cores, did not enhance 7-ethoxycoumarin metabolism in rat liver slices. In this study, the optimal slice thickness was 175μm, with higher rates of 7-ethoxycoumarin metabolism being observed than with 250μm thick slices, which are often used for studies of xenobiotic metabolism. Variable results were obtained with slices of around 100–120μm thickness, which may be attributable to the ratio between intact hepatocytes and cells damaged by the slicing procedure in these very thin slices.

scholarly journals Dietary conjugated linoleic acid (CLA) induces apoptosis of colonic mucosa in 1,2-dimethylhydrazine-treated rats: a possible mechanism of the anticarcinogenic effect by CLA

2001 ◽  
Vol 86 (5) ◽  
pp. 549-555 ◽  
Author(s):  
Hyun S. Park ◽  
Ji H. Ryu ◽  
Yeong L. Ha ◽  
Jung H. Y. Park
Keyword(s):  
Linoleic Acid ◽  
Conjugated Linoleic Acid ◽  
Control Diet ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Tumour Incidence ◽  
Sprague Dawley Rats ◽  
Dietary Conjugated Linoleic Acid

One of the objectives of the present study was to investigate whether 1 % conjugated linoleic acid (CLA) in the diet reduced tumour incidence in the colon of 1,2-dimethylhydrazine (DMH)-treated rats. Colon cancer was induced by injecting 6-week-old, male, Sprague–Dawley rats with 15 mg/kg DMH twice per week for 6 weeks. They were fed either 1 % CLA or a control diet ad libitum for 30 weeks. Dietary CLA significantly decreased colon tumour incidence (P<0·05). Our second objective was to investigate whether apoptosis in the colon mucosa of DMH-treated rats was affected by the amount of dietary CLA and whether the changes in apoptosis were related to those in fatty acid-responsive biomarkers. For this purpose, rats were killed after being fed a diet containing 0 %, 0·5 %, 1 % or 1·5 % CLA for 14 weeks. CLA was undetected in the mucosa of rats fed the 0 % CLA diet and increased to 5·9 mg/g phospholipid in rats fed the 0·5 % diet. The apoptotic index estimated by the terminal deoxynucleotidyl transferase-mediated dUTP nick and labelling technique was increased by 251 % and the 1,2-diacylglycerol content was decreased by 57 % in rats fed 0·5 % CLA. No further changes in these variables were observed when CLA in the diet was raised to 1·0 % or 1·5 %. However, dietary CLA decreased mucosal levels of prostaglandin E2, thromboxane B2 and arachidonic acid in a dose-dependent manner. The present data indicate that dietary CLA can inhibit DMH-induced colon carcinogenesis by mechanisms probably involving increased apoptosis.

Effects of Blood Glucose Changes and Physostigmine on Anesthetic Requirements of Halothane in Rats 

1997 ◽  
Vol 87 (2) ◽  
pp. 354-360 ◽  
Author(s):  
Yumiko Ishizawa ◽  
Shuichiro Ohta ◽  
Hiroyuki Shimonaka ◽  
Shuji Dohi
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Glucose Level ◽  
Minimum Alveolar Concentration ◽  
Severe Hypoglycemia ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Control Value ◽  
Sprague Dawley Rats ◽  
Brain Acetylcholine

Background Although hyper- and hypoglycemia induce neurophysiologic changes, there have been no reports on the effects of blood glucose changes on anesthetic requirements. This study examined the effects of hyper- and hypoglycemia on the minimum alveolar concentration (MAC) of halothane in rats. In addition, based on a previous finding that the level of brain acetylcholine was reduced during mild hypoglycemia, the authors examined the influence of physostigmine on MAC during hypoglycemia. Methods In Sprague-Dawley rats, anesthesia was induced and maintained with halothane in oxygen and air. The MAC was determined by observing the response to tail clamping and tested during mild hypoglycemia (blood glucose level, 60 mg/dl) and hyperglycemia (blood glucose level, 300 and 500 mg/dl) induced by insulin and glucose infusion, respectively (experiment 1). The effects of 0.3 and 1.0 mg/kg physostigmine given intraperitoneally on MAC were examined in rats with mild and severe hypoglycemia (blood glucose level, 60 and 30 mg/dl; experiment 2). Results In experiment 1, mild hypoglycemia significantly reduced the MAC of halothane (0.76 +/- 0.03%) compared with the control value (0.92 +/- 0.04%), but hyperglycemia did not change MAC. In experiment 2, mild and severe hypoglycemia reduced MAC of halothane in a degree-dependent manner. Physostigmine (1 mg/kg) had no effect on MAC regardless of blood glucose level, but 0.3 mg/kg reduced MAC. Conclusions Hypoglycemia reduced anesthetic requirements in a degree-dependent manner, whereas hyperglycemia had no effects. Although the mechanism of hypoglycemic MAC reduction needs further investigations, physostigmine studies suggest that this may not be related to inhibition of cholinergic transmission.

The Hepatoprotective Role of Warburgia salutaris and Iso-Mukaadial Acetate on Carbon tetrachloride Intoxicated Rats Model

2021 ◽  
Vol 17 ◽  
Author(s):  
Gideon Ayeni ◽  
Mthokozisi Blessing Cedric Simelane ◽  
Shahidul Islam ◽  
Ofentse Jacob Pooe
Keyword(s):  
Carbon Tetrachloride ◽  
Hepatic Injury ◽  
Antioxidant Properties ◽  
Hepatic Necrosis ◽  
Protective Role ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Isolated Compound

Background: Medicinal plants together with their isolated bioactive compounds are known for their antioxidant properties which constitute therapeutic agents that are routinely employed in the treatment of liver diseases. Aims of the Study: The current study sought to explore the protective role of Warburgia salutaris and its isolated compound, iso-mukaadial acetate against carbon tetrachloride (CCl4)-induced hepatic injury. Methods: Thirty-five male Sprague Dawley rats were divided into seven groups of five animals each and injected with CCl4 to induce hepatic injury. Results: Treatment with the crude extract of W. salutaris and of iso-mukaadial acetate significantly reduced the levels of alkaline phosphatase, alanine and aspartate aminotransaminases, total bilirubin and malondialdehyde in a dose dependent manner, when compared to untreated groups. Liver histology revealed a reduction in hepatic necrosis and inflammation. Conclusion: The current investigation has demonstrated that W. salutaris extract and iso-mukaadial acetate could mitigate the acute liver injury inflicted by a hepatotoxic inducer in rats.

Changes in [Ca2+]i induced by several glucose transport-enhancing stimuli in rat epitrochlearis muscle

2003 ◽  
Vol 94 (5) ◽  
pp. 1813-1820 ◽  
Author(s):  
Shin Terada ◽  
Isao Muraoka ◽  
Izumi Tabata
Keyword(s):  
Glucose Transport ◽  
Quantitative Information ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Concentration Dependent Manner ◽  
Fura 2 ◽  
Sprague Dawley Rats ◽  
Intracellular Ca ◽  
Resting Muscle ◽  
Krebs Henseleit Buffer

The purpose of the present investigation was to establish a method for estimating intracellular Ca2+ concentrations ([Ca2+]i) in isolated rat epitrochlearis muscles. Epitrochlearis muscles excised from 4-wk-old male Sprague-Dawley rats were loaded with a fluorescent Ca2+indicator, fura 2-AM, for 60–90 min at 35°C in oxygenated Krebs-Henseleit buffer. After fura 2 loading and subsequent 20-min incubation, the intensities of 500-nm fluorescence, induced by 340- and 380-nm excitation lights (Ftotal340 and Ftotal380), were measured. The fluorescences specific to fura-2 (Ffura 2340 and Ffura 2380) were calculated by subtracting the non-fura 2-specific component from Ftotal340 and Ftotal380, respectively. The ratio of Ffura 2340 to Ffura 2380 was calculated as R, and the change in the ratio from the baseline value (ΔR) was used as an index of the change in [Ca2+]i. In resting muscle, ΔR was stable for 60 min. Incubation for 20 min with caffeine (3–10 mM) significantly increased ΔR in a concentration-dependent manner. Incubation with hypoxic Krebs-Henseleit buffer for 10–60 min significantly elevated ΔR, depending on the duration of the incubation. Incubation with 50 μM N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide for 20 min significantly elevated ΔR ( P < 0.05). No significant increases in ΔR were observed during incubation for 20 min with 2 mM 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside or with 2 mU/ml insulin. These results demonstrated that, by using the fura 2-AM fluorescence method, the changes in [Ca2+]i can be monitored in the rat epitrochlearis muscle and suggest that the method can be utilized to observe quantitative information regarding [Ca2+]i that may be involved in contraction- and hypoxia-stimulated glucose transport activity in skeletal muscle.

Glutamine promotes triglyceride absorption in a dose-dependent manner

2002 ◽  
Vol 282 (2) ◽  
pp. G317-G323 ◽  
Author(s):  
Jeffrey B. Schwimmer ◽  
Looi Ee ◽  
Shuqin Zheng ◽  
Patrick Tso
Keyword(s):  
Amino Acid ◽  
Amino Acid Mixture ◽  
Lipid Absorption ◽  
Acid Mixture ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Feeding Tubes ◽  
Mesenteric Lymph ◽  
Sprague Dawley Rats ◽  
Dose Dependent

Dietary proteins may play a role in lipid absorption. Whether amino acids are specifically involved is unknown. We hypothesized that enterally administered l-glutamine (l-Gln) given with a lipid meal increases triglyceride (TG) absorption in rats. Mesenteric lymph fistulae and gastroduodenal feeding tubes were placed in adult male Sprague-Dawley rats. The animals received an enteral bolus of Intralipid (5 ml) followed by enteral infusion of increasing concentrations of l-Gln in saline (0, 85, 170, or 340 mM) or equimolar concentrations of the inactive isomer d-Gln or an essential amino acid mixture without Gln. Lymph was collected continuously for 6 h and analyzed for TG content. Animals infused with 85 mM l-Gln had a 64% increase in total TG output vs. controls ( P < 0.05) despite no difference in lymph flow rate. Total TG output for animals infused with 340 mMl-Gln declined by 43% vs. controls ( P < 0.05). The effect of Gln in promoting lymphatic fat transport is specific to l-Gln and not shared by d-Gln or an equivalent amino acid mixture. l-Gln is capable of either promoting or impairing lymphatic TG transport in a dose-dependent manner.

Cinnamomum cassia ameliorates Ni-NPs-induced liver and kidney damage in male Sprague Dawley rats

2020 ◽  
Vol 39 (11) ◽  
pp. 1565-1581
Author(s):  
S Iqbal ◽  
F Jabeen ◽  
C Peng ◽  
MU Ijaz ◽  
AS Chaudhry
Keyword(s):  
Dependent Manner ◽  
Sprague Dawley ◽  
Cinnamomum Cassia ◽  
Preliminary Information ◽  
Sprague Dawley Rats ◽  
Liver And Kidney ◽  
Altered Blood ◽  
Biochemical Analyses ◽  
Dose Dependent ◽  
Different Doses

Nickel nanoparticles (Ni-NPs) have been widely used in various industries related to electronics, ceramics, textiles, and nanomedicine. Ambient and occupational exposure to Ni-NPs may bring about potential detrimental effects on animals and humans. Thus, there is a growing effort to identify compounds that can ameliorate NPs-associated pathophysiologies. The present study examined Cinnamomum cassia ( C. cassia) bark extracts (CMBE) for its ameliorative activity against Ni-NPs-induced pathophysiological and histopathological alterations in male Sprague Dawley rats. The biochemical analyses revealed that dosing rats with Ni-NPs at 10 mg/kg/body weight (b.w.) significantly altered the normal structural and biochemical adaptations in the liver and kidney. Conversely, supplementations with CMBE at different doses (225, 200, and 175 mg/kg/b.w. of rat) ameliorated the altered blood biochemistry and reduced the biomarkers of liver and kidney function considerably ( p < 0.05) in a dose-dependent manner. However, the best results were at 225 mg/kg/b.w. of rat. The study provided preliminary information about the protective effect of C. cassia against Ni-NPs indicated liver and kidney damages. Future investigations are needed to explore C. cassia mechanism of action and isolation of single constituents of C. cassia to assess their pharmaceutical importance accordingly.

scholarly journals Collagen-Induced Reduction in Rat Circulating Platelet Count: Influence of Platelet Function Inhibitors

1977 ◽  
Author(s):  
I.B. Holmes
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Test System ◽  
Collagen Fibrils ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Dose Dependent ◽  
Double Lumen Cannula ◽  
Antiinflammatory Compound

The effect on circulating platelet count of repeated intravenous infusions of collagen fibrils was measured in male OFA Sprague-Dawley rats (400-550 g). Citrated blood was pumped from the left carotid artery of anaesthetized animals, via a siliconized double-lumen cannula, into the manifold of a Technicon Autocounter, for continuous registration of platelet count. Native collagen fibrils (Collagenreagent ‘Horm’) were infused intravenously for 1 min at 15 min intervals. Successive increasing collagen doses (20-320 pg/kg) induced dose-dependent reduction in platelet count, measured as absolute platelet number disappearing from the circulation. Repeated infusion of collagen 160 pg/kg produced constant, partially reversible, reduction in platelet count. Several known inhibitors of platelet aggregation were investigated in the described test system. Collagen effects were inhibited in a dose-dependent manner to a maximum of 50-60 %, and drug activity was thus quantitated on the basis of dose producing 30 % inhibition (ID30): prostaglandin E1 (1.6 pg/kg/min i.v. infusion), SH-869 (1.1 mg/kg i.v.), aspirin (33.1 mg/kg p.o.), proquazone, a new non-steroidal antiinflammatory compound (5.0 mg/kg p.o.). That part of the collagen response not inhibited might be attributed to the initial phase of platelet adhesion to collagen, known to be relatively refractive to platelet function inhibitors.

Protective Effect of Reduced Glutathione against CIS-Dichlorodiammine Platinum (II)–Induced Nephrotoxicity and Lethal Toxicity

1983 ◽  
Vol 69 (2) ◽  
pp. 105-111 ◽  
Author(s):  
Franco Zunino ◽  
Odoardo Tofanetti ◽  
Adriana Besati ◽  
Ennio Cavalletti ◽  
Giuseppina Savi
Keyword(s):  
Reduced Glutathione ◽  
Body Weight Loss ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Antitumor Effects ◽  
Partial Protection ◽  
Lethal Toxicity ◽  
Sprague Dawley Rats ◽  
Serum Blood Urea Nitrogen ◽  
Dose Dependent

Pretreatment of Swiss mice and Sprague-Dawley rats with glutathione (GSH) reduced the acute lethal toxicity of cis-dichlorodiammine platinum (II) (cis-DDP) in a dose-dependent manner. The protection was accompanied by reduction of both body weight loss and by reduction of nephrotoxicity, as measured by a rise in serum blood urea nitrogen (BUN), creatinine levels and by histopathologic changes, which occurred 4 days following cis-DDP treatment. The antitumor effects of cis-DDP on experimental tumor models (P388 and Gross leukemia) were not significantly altered by GSH treatment. It is suggested that the partial protection by GSH from acute toxicity of the antitumor drug is directly related to protection of renal function.

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