Ro 44-9883, a New Non-Peptidic GPIIb-GPIIIa Antagonist Prevents Platelet Loss in a Guinea Pig Model of Extracorporeal Circulation

1993 ◽  
Vol 70 (05) ◽  
pp. 817-821 ◽  
Author(s):  
Jean-P Carteaux ◽  
Beat Steiner ◽  
Sébastien Roux
Keyword(s):  
Platelet Count ◽  
Extracorporeal Circulation ◽  
Guinea Pigs ◽  
Low Dose ◽  
Treated Group ◽  
In Vivo Model ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Contact Activation

SummaryExtensive contact between blood and artificial surfaces causes platelet activation and depletion. The aim of the present study was to test the efficacy of Ro 44-9883, a potent and selective peptidomimetic GPIIb-IIIa antagonist, in preventing platelet loss in guinea pigs undergoing extracorporeal circulation (ECC) with bubble oxygenation. In 15 guinea pigs, an arterio-arterial shunt was created and perfused for 1 h from the aortic arch to the descending aorta. The guinea pigs were divided into three groups: A control group receiving only heparin as an i.v. bolus, a low dose-treated group and a high dose-treated group receiving in addition to heparin and before starting ECC, 1 or 7 mg/kg Ro 449883 as an i.v. bolus, respectively. In the control group, the platelet count at 30 and 60 min of ECC was dramatically decreased (35 ± 4% and 25 ± 3% of initial value). In the low dose-treated group, Ro 44-9883 partially prevented the drop in platelet count (69 ± 8% and 54 ± 9%; p <0.05) whereas in the high dose-treated group, the platelet count was normal at 30 min (97 ± 8%) and only slightly decreased at 60 min (80 ± 7%). Mean arterial pressure and hematocrit were not significantly different between groups during the experiment. We conclude that i) ECC in guinea pigs provides an interesting in-vivo model for studying platelet loss by contact activation and ii) Ro 44-9883 prevents platelet loss during ECC in a dose dependent manner.

scholarly journals PERSPECTIVE STUDY OF THE AgNPs EFFECT ON THE MATERNAL AND EMBRYONIC DEVELOPMENT IN ALBINO RATS

2019 ◽  
Vol 50 (6) ◽  
Author(s):  
Ali & et al.
Keyword(s):  
Low Dose ◽  
Active Form ◽  
Treated Group ◽  
Control Group ◽  
Albino Rats ◽  
High Dose ◽  
Treatment Groups ◽  
Gestational Period ◽  
Pregnant Females ◽  
Post Implantation

 This study was aimed to displayed effect of this nanoparticles on pregnant mother and embryos. All females administration of AgNPs suspension orally during the gestational period (for 21day) in two doses low 2mg and high dose 20 mg /Kg body weight and the control group received D.W only. The pregnant females (60 females) include the control group and the treated group  was subdivided in to two groups, pre and post implantation and all the mothers weighted along the study. The embryos and their brains after retrieved weighted and the crow-rump length (CRL) measurement also. The results showed that the active form of Ag can be transport the placental barrier and blood brain barrier (BBB). This nanoparticles showed adverse effect and produced decreased in mothers weights in low dose 2mg/Kg/ B.Wt and higher dose 20mg/Kg/ B.Wt. Weights of embryos were lower clearly after exposure to AgNPs compare to control group. On the other hand, the weights of embryo's brain were decreased compare of control group in both doses. The CRL of embryos lowered after exposure to AgNPs in treatment groups when compare to control group.

Comparison of Antileukotrienes and Antihistamines in the Treatment of Allergic Rhinitis

2007 ◽  
Vol 21 (4) ◽  
pp. 439-443 ◽  
Author(s):  
Ching-Yin Ho ◽  
Ching-Ting Tan
Keyword(s):  
Allergic Rhinitis ◽  
Low Dose ◽  
Treated Group ◽  
Nasal Symptom ◽  
Controlled Study ◽  
Control Group ◽  
High Dose ◽  
Nasal Resistance ◽  
Before And After ◽  
Nasal Secretions

Background The aim of this study was to compare the effect of antileukotriene (anti-LT), antihistamine, and a combination of anti-LT and antihistamine on the symptoms and nasal resistance in allergic rhinitis patients. Methods We performed a placebo-controlled study, with 120 persistent, moderate to severe allergic rhinitis patients randomly selected to receive the different treatments for 4 weeks: no treatment, 10 mg of cetirizine once per day, 20 mg of zafirlukast once per day, 20 mg of zafirlukast twice per day, a combination of 20 mg of zafirlukast and 10 mg of cetirizine once per day, or a combination of 20 mg of zafirlukast twice per day and 10 mg cetirizine once per day. The nasal secretion nitric oxide (NO) concentration, nasal symptom score, and nasal resistance were measured before and after treatment. Results Total symptom scores improved in each treated group compared with the control group (p < 0.05). Nasal obstruction significantly improved in the anti-LT-treated groups (p < 0.05). High-dose anti-LT or the combination of low-dose anti-LT and antihistamine significantly improved allergy symptoms compared with no treatment, low-dose anti-LT, or antihistamine alone (p < 0.05). Furthermore, anti-LT decreased NO concentration in nasal secretions (p < 0.05), regardless of the dose administered. Conclusion These results suggest that high-dose anti-LT alone or the combination of low-dose anti-LY and antihistamine can effectively treat allergic rhinitis.

scholarly journals Study on Ameliorative Effect of Febuxostat on Gout Induced Model in Broiler Chicks

2017 ◽  
Vol 13 (01) ◽  
Author(s):  
M. K. Patel ◽  
D. J. Dave ◽  
R. C. Rathod ◽  
B. P. Joshi ◽  
D. J. Ghodasara
Keyword(s):  
Body Weight ◽  
Low Dose ◽  
Body Weight Gain ◽  
Treated Group ◽  
Group Iv ◽  
Control Group ◽  
High Dose ◽  
Broiler Chicks ◽  
Ameliorative Effect ◽  
Group Ii

This work was conducted on six groups of day-old Cobb-400 broiler chicks to study the ameliorative effect of febuxostat on gout induced model. Clinical signs were noticed in birds of diclofenac control group II and low dose febuxostat treated group IV. During the study, 27.77% and 22.22% mortality were observed in diclofenac control group II and low dose febuxostat treated group IV, respectively. Febuxostat control group III and febuxostat (medium and high dose) treated groups V and VI had no mortality. Reduction in body weight gain and feed intake was observed in diclofenac control group II as compared to without treatment control group I at the end of every week during the experimental period of 21 days. Reduction in body weight gain and feed intake was observed in low dose febuxostat treated group IV as compared to control group at the end of 1st week. The average FCR was higher in diclofenac control group II (2.54) and low dose febuxostat treated group IV (2.14) as compared to control group (2.00). Kidney: body weight ratio was significantly high in diclofenac control group II as compared to control group at the end of experiment. Gross and microscopic lesions of visceral gout were mainly observed in chicks that died during the experiment from diclofenac control group II and low dose febuxostat treated group IV. The overall lesions showed that diclofenac was nephrotoxic and hepatotoxic in nature. Febuxostat at lower than the therapeutic dose did not prevent nephrotoxicity and hepatotoxicity caused by diclofenac leading to visceral gout. Febuxostat control III and febuxostat (medium and high dose) treated groups V and VI did not reveal any pathomorphological changes. Judicious use of febuxostat is safe in poultry birds between the limit of 4 mg/kg and 6 mg/kg

scholarly journals Dose-dependent effects of adalimumab in neonatal rats with hypoxia/reoxygenation-induced intestinal damage

2020 ◽  
Author(s):  
Halil Kocamaz ◽  
Özmert MA Özdemir ◽  
Nilay Şen Türk ◽  
Yaşar Enli ◽  
Barbaros Şahin ◽  
...  
Keyword(s):  
Low Dose ◽  
Treated Group ◽  
Intestinal Injury ◽  
Control Group ◽  
High Dose ◽  
Intestinal Damage ◽  
Neonatal Rats ◽  
Tnf Α ◽  
Dose Dependent ◽  
Hypoxia Reoxygenation

Tumor necrosis factor-alpha (TNF-α) has an important role in hypoxia/reoxygenation (H/R)-induced intestinal damage. It was shown that blocking TNF-α with infliximab has beneficial effects on experimental necrotizing enterocolitis and hypoxic intestinal injury. However, there is no data about the effect of adalimumab on H/R-induced intestinal damage. Therefore, we aimed to determine potential dose-dependent benefits of adalimumab in such damage in neonatal rats. Wistar albino rat pups were assigned to one of the four groups: control group, hypoxia group, low-dose adalimumab (5 mg/kg/day) treated group (LDAT), and high-dose adalimumab (50 mg/kg/day) treated group (HDAT). On the fourth day of the experiment, all rats except for the control group were exposed to H/R followed by euthanasia. Malondialdehyde (MDA), myeloperoxidase (MPO), TNF-α, total antioxidant capacity (TAC), and total oxidant capacity (TOC) were measured in intestinal tissue. TAC and TOC values were used to calculate the oxidative stress index (OSI). Histopathological injury scores (HIS) were also evaluated in the tissue samples. MDA levels were significantly lower in the LDAT and HDAT groups (p < 0.001). TNF-α levels were significantly lower in the LDAT group (p < 0.001). OSI was significantly higher in the H/R group than in the control and LDAT groups (p < 0.001). Mean HIS values in the LDAT group were significantly lower than those in the H/R and HDAT groups (p < 0.001). This experimental study showed that low-dose adalimumab appears to have a beneficial effect on intestinal injury induced with H/R in neonatal rats.

scholarly journals The effect of red wine extract, resveratrol, on the degree and rate of orthodontic tooth movement in guinea pigs

2015 ◽  
Vol 5 ◽  
pp. 181-189
Author(s):  
Isidro Alex C. Urriquia ◽  
Lotus D. Llavore
Keyword(s):  
Guinea Pigs ◽  
Low Dose ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Control Group ◽  
High Dose ◽  
Male Adult ◽  
Significant Difference ◽  
The Mean ◽  
And Control

ObjectiveAn animal trial, its protocol approved by the Institutional Animal Care and Use Committee of the U.P. National Institutes of Health (IACUC Protocol No. 2010-008), was employed to investigate the effects of resveratrol on the degree and rate of orthodontic tooth movement in guinea pigs.Materials and MethodsEighteen male adult guinea pigs were randomly allocated into 3 groups: low dose, high dose, and control groups. A 0.016″ titanium molybdenum alloy wire formed into a helical torsion spring with a coil, with the loops cemented onto the maxillary incisors of the animals, served as the orthodontic appliance. Daily oral administration of resveratrol was provided to the low dose (0.047 mg/kg) and high dose (0.47 mg/kg) groups, while water was provided to the control group. Measurements were taken everyday at the interproximal area at the level of the incisal edge using a measuring caliper.ResultsThe results of the ANOVA showed no statistically significant differences in the mean measurements of tooth separation among the three groups from day 2 (P=0.966) to day 8 (P=0.056). However, starting from day 9 (P=0.049) until day 18 (P=0.000), there was a significant difference in the mean tooth separation among the test groups.ConclusionUsing the LSD, it was noted that the low dose and the high dose groups have similar degrees of mean tooth separation, with the control group being significantly different from the two.

scholarly journals Antioxidant Property of the Egyptian Propolis Extract Versus Aluminum Silicate Intoxication on a Rat’s Lung: Histopathological Studies

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5821
Author(s):  
Ali H. Abu Almaaty ◽  
Yasmin M. Abd El-Aziz ◽  
Nahed A. Omar ◽  
Ahmed M. Abdeen ◽  
Hala Afifi ◽  
...  
Keyword(s):  
Low Dose ◽  
Antioxidant Properties ◽  
Treated Group ◽  
Positive Control ◽  
Positive Control Group ◽  
Aluminum Silicate ◽  
Control Group ◽  
Albino Rats ◽  
High Dose ◽  
Propolis Extract

In this study, we evaluated the inflammatory responses induced by aluminum silicate (AS) cytotoxicity in rat lungs. The prophylactic effect of propolis extract was evaluated in 60 adult male albino rats. The rats were divided into six groups: (1) a normal, healthy control group; (2) a normal group fed with 200 mL of propolis extract/Kg; (3) a low-dose positive control group injected with 5 mg/kg of AS; (4) a treated group given propolis and a low dose of AS; (5) a high-dose positive control group injected with 20 mg/kg of AS; and (6) a treated group given propolis with a high-dose of AS. At the end of the two-month experiment, the rats’ lungs were removed. For each pair of lungs, one portion was subjected to biochemical analysis and the other underwent hematoxylin and eosin (H&E) staining in order to study its histology. The rats that received AS doses displayed significant disorders in their antioxidant contents as well as in their enzymatic activities and their histopathological structures revealed severe damage to their lung tissues. Upon the rats being treated with propolis, the enzymatic and antioxidant contents improved and partial improvements in the lung structures appeared, including minimized congestion, a reduced hemorrhage of blood vessels and preserved bronchioles, alveolar ducts, and alveoli. The prophylactic effectiveness of propolis extract on the cytotoxicity of AS, owing to the antioxidant properties of propolis, were studied.

Role of ET(A) and ET(B) receptors in endothelin-1-induced adrenal catecholamine secretion in vivo

1997 ◽  
Vol 272 (4) ◽  
pp. R1290-R1297 ◽  
Author(s):  
N. Yamaguchi
Keyword(s):  
High Performance ◽  
Low Dose ◽  
Dose Range ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Experimental Conditions ◽  
Chromatography Method ◽  
Liquid Chromatography Method

The present study was designed to test whether endothelin (ET) A and/or B receptors in the adrenal medulla are functionally involved in ET-1-induced catecholamine (CA) release in anesthetized dogs. ET-1 was locally infused into the gland via the left adrenolumbar artery. Plasma CA in adrenal venous and aortic blood was determined by a high-performance liquid chromatography method. In the control group, the local infusion of ET-1 (0.5 microg, 0.4 microM) resulted in a significant increase in CA output. In the presence of a low dose of BQ-123 (5 microg, 16.4 microM), the ET-1-induced CA response was significantly attenuated by approximately 80%. With a high dose of BQ-123 (50 microg, 164 microM), the CA response was further blocked by approximately 95%. This inhibition was significantly greater than that obtained with the low dose of BQ-123. By contrast, a low dose of BQ-788 (5 microg, 15.1 microM) did not significantly affect the CA response. With a high dose of BQ-788 (50 microg, 151 microM), the CA response was only partially inhibited by approximately 70%. The results indicate that BQ-123 significantly inhibited ET-1-induced adrenal CA release in a dose-dependent manner. With the low doses, the CA response was markedly inhibited by BQ-123 but remained unchanged in the presence of BQ-788. Moreover, the high dose of BQ-123 virtually abolished the CA response, whereas BQ-788 failed to do so within the dose range tested. The present study suggests that the ET(A) receptor may play a predominant role in mediating the ET-1-induced CA secretion in the canine adrenal gland in vivo, although the possible involvement of the ET(B) receptor could not completely be excluded under the present experimental conditions.

scholarly journals Metabolomics of Aurantio-Obtusin-Induced Hepatotoxicity in Rats for Discovery of Potential Biomarkers

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3452 ◽  
Author(s):  
Longlong Xu ◽  
Jian Li ◽  
Xianglin Tang ◽  
Yuguang Wang ◽  
Zengchun Ma ◽  
...  
Keyword(s):  
Liver Injury ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Sprague Dawley ◽  
Blank Control Group ◽  
Hematological Indices ◽  
Main Components ◽  
Kg Medium

Aurantio-obtusin is an anthraquinone derived from Cassia obtusifolia (cassiae semen). It is also used as a tool and a detection index for the identification of cassiae semen, as stipulated by the Chinese Pharmacopoeia. Anthraquinones, the main components in cassiae semen, have been reported to show hepatotoxicity. This study investigates the hepatotoxicity of aurantio-obtusin in male Sprague–Dawley rats. We randomly divided the animals into a blank control group and treated three test groups with different doses of aurantio-obtusin: Low dose (4 mg/kg), medium dose (40 mg/kg), and high dose (200 mg/kg). Each group was treated with aurantio-obtusin for 28 days, whereas the control group was administered an equal volume of 0.5% carboxymethyl cellulose sodium salt (CMC-Na) aqueous solution. Subsequently, we conducted biochemical, hematological, and pathological investigations and determined the weight of different organs. We used serum metabolomics to identify possible biomarkers related to hepatotoxicity. The low-dose group showed no significant liver injury, whereas the medium- and high-dose groups manifested obvious liver injury. Compared with the control group, the test groups showed an increase in alanine transaminase, aspartate transaminase, and alkaline phosphatase levels. The liver organ coefficient also significantly increased. Additionally, we found significant changes in the hematological indices. Metabolomics analysis showed that aurantio-obtusin induced 28 endogenous markers related to liver injury. Our data indicate that aurantio-obtusin induces hepatotoxicity in rat liver in a dose-dependent manner and is mediated by pathways involving bile acids, fatty acids, amino acids, and energy metabolism. In particular, changes in bile acid content during treatment with therapeutic agents containing aurantio-obtusin deserve increased attention.

Protective Effects of Flavonoids from Lotus Leaf against Exercise-Induced Oxidant Stress in Muscle of Mice

2013 ◽  
Vol 448-453 ◽  
pp. 1089-1092 ◽  
Author(s):  
Lan Zhang
Keyword(s):  
Low Dose ◽  
Oxidant Stress ◽  
Treated Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Lotus Leaf ◽  
Swimming Time ◽  
Exercise Induced ◽  
Different Doses

The main purpose of this study was to examine the effect of flavonoids from Lotus leaf (FFL) on exercise-induced oxidant stress in mice. 32 mice were randomly divided into 4 groups: control group, FLL low dose treated group, FLL middle dose treated group and FLL high dose treated group. The control group was given distilled water and the treated groups were given different doses of FLL (50, 100, 150 mg/kg) by gavage once a day for 28 days. 28 day later, mice were made to swim until being exhausted, and exhaustive swimming time, malondialdehyde (MDA) levels, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in muscle were measured. The data showed that that FFL increase the exhaustive swimming time and could elevate the exercise tolerance, as well as decrease the MDA levels, increase SOD and GSH-Px activities in muscle of mice. These results indicated that FFL has a protective effect against exercise-induced oxidative stress.

scholarly journals Effects of DI-(2-Ethylhexyl) Phthalate on Rat Ovarian Function

2011 ◽  
Vol 30 (4) ◽  
pp. 309-316
Author(s):  
Cheng-kang Xu ◽  
Xiao-hong Wang ◽  
Shuang-bo Tang
Keyword(s):  
Estrous Cycle ◽  
Dose Group ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Dependent Manner ◽  
Short Course ◽  
Long Course ◽  
Ethylhexyl Phthalate ◽  
Medium Dose

Effects of DI-(2-Ethylhexyl) Phthalate on Rat Ovarian FunctionThis study aimed to evaluate the effects of di-(2-ethylhexyl)phthalate (DEHP) on estrous cycle, sex hormone levels and ovary histological features. A total of 80 female SD rats were randomly divided into 8 groups (n=10 per group): short-course control group, short-course low-dose group, short-course medium-dose group, and short-course high-dose group, long-course control group, long-course low-dose group, long-course medium-dose group and long-course high-dose group. Intragastrical DEHP was administrated at 1000 mg/kg/d (low dose), 2000 mg/kg/d (medium dose) and 3000 mg/kg/d (high dose) independently for 14 days (short course) or 28 days (long course). Rats in control groups were untreated. Vaginal smearing was used to detect the estrous cycle and rats were weighed at every Monday and Thursday to evaluate the growth status. At the end of study, rats were sacrificed and bilateral ovaries were obtained for histological examination. In addition, ELISA determined levels of serum progesterone, estradiol, testosterone, follicle stimulating hormone and luteinizing hormone. DEHP treatment limited body weight gain (p<0.05), prolonged the estrous cycle (p<0.05), decreased the ovarian mass index (p<0.05) and ovarian weight. No evident degeneration, necrosis or other pathological features were found in the ovaries. The testosterone levels were decreased by DEHP treatment in a dose dependent manner. DEHP treatment could increase serum testosterone level, inhibit ovulation and prolong the estrous cycle of rats, exerting reproductive toxicity in a dose dependent manner. We speculate DEHP can affect the endocrine regulatory function of the ovary and limit the body weight gain, resulting in chronic toxicity.

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