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

Author(s):  
Halil Kocamaz ◽  
Özmert MA Özdemir ◽  
Nilay Şen Türk ◽  
Yaşar Enli ◽  
Barbaros Şahin ◽  
...  

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.

2014 ◽  
Vol 5 (3) ◽  
pp. 315-322 ◽  
Author(s):  
T. Pan ◽  
H.Y. Guo ◽  
H. Zhang ◽  
A.P. Liu ◽  
X.X. Wang ◽  
...  

The aim of this study was to investigate the alleviating effect of Lactobacillus paracasei subsp. paracasei LC-01 (LC-01) on the murine model of colitis induced by dextran sulphate sodium (DSS). 50 pathogen-free, 6-week-old male BALB/c mice were divided randomly into 5 groups, including a control group and four DSS-LC-01-treated groups (DSS, DSS-106, DSS-108, and DSS-1010 with 0, 1×106, 1×108 and 1×1010 cfu/ml LC-01, respectively). To test the effectiveness of LC-01 as a prophylactic it was administered for 7 days before the onset of the disease in DSS-LC-01-treated mice. After 7 days, colitis was induced by administration of 2.5% (w/v) DSS in drinking water for a further 7 days. The disease activity index (DAI), histological score, myeloperoxidase (MPO) activity and the level of the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumour necrosis factor α (TNF-α) were measured. DAI, histological scores and MPO activity of mice treated with a medium or high dose of LC-01 were significantly lower compared to a low-dose of LC-01 and DSS treatment alone (P<0.05). Colon length shortening could be prevented with increasing dose of LC-01. In addition, the levels of IL-1β and TNF-α were suppressed significantly by treatment with a medium and high dose of LC-01. However, no significant difference in the indices mentioned above were observed between a low dose of LC-01 and treatment with DSS alone (P≯0.05). An appropriate dose of LC-01 can prevent intestinal damage in mice with DSS-induced colitis. The expression of inflammatory cytokines related to pathogenesis of DSS-induced colitis decreased following treatment with LC-01.


1987 ◽  
Vol 17 (4) ◽  
pp. 869-873 ◽  
Author(s):  
C. Schmauss ◽  
J.-C. Krieg

SynopsisIn 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.


2003 ◽  
Vol 284 (2) ◽  
pp. R550-R557 ◽  
Author(s):  
Roy D. Goldfarb ◽  
Thomas S. Parker ◽  
Daniel M. Levine ◽  
Dana Glock ◽  
Imran Akhter ◽  
...  

Lipoprotein phospholipid (PL) plays a major role in neutralization of endotoxin. This study tested the hypothesis that prophylactic administration of a PL-enriched emulsion (PRE), which augments PL content of serum lipoproteins and neutralizes endotoxin in vitro, would preserve cardiovascular function and improve survival in porcine septic peritonitis. A control group was compared with low-, mid-, and high-dose treatment groups that received PRE by primed continuous infusion for 48 h. A fibrin clot containing live Escherichia coli 0111.B4 was implanted intraperitoneally 30 min after the priming dose. Survival increased in a dose-dependent manner and was correlated with serum PL. Infused PL was associated with high-density lipoprotein in the low-dose group and all serum lipoproteins at higher doses. Treatment significantly lowered serum endotoxin and tumor necrosis factor (TNF)-α, preserved cardiac output and ejection fraction, and attenuated increases in systemic and pulmonary vascular resistances. This study demonstrated that augmentation of lipoprotein PL via administration of PRE improved survival and offered a novel therapeutic approach to sepsis.


1991 ◽  
Vol 71 (1) ◽  
pp. 83-93 ◽  
Author(s):  
P. Van der Linden ◽  
E. Gilbart ◽  
E. Engelman ◽  
D. Schmartz ◽  
J. L. Vincent

The present study tested the hypothesis that anesthetic agents can alter tissue O2 extraction capabilities in a dog model of progressive hemorrhage. After administration of pentobarbital sodium (25 mg/kg iv) and endotracheal intubation, the dogs were paralyzed with pancuronium bromide, ventilated with room air, and splenectomized. A total of 60 dogs were randomized in 10 groups of 6 dogs each. The first group served as control (C). A second group (P) received a continuous infusion of pentobarbital (4 mg.kg-2.h-2), which was started immediately after the bolus dose. Three groups received enflurane (E), halothane (HL), or isoflurane (I) at the end-tidal concentration of 0.7 minimum alveolar concentration (MAC). The sixth group received halothane at the end-tidal concentration of 1 MAC (HH). Two groups received intravenous alfentanil at relatively low dose (AL) or high dose (AH). The last two groups received intravenous ketamine at either relatively low dose (KL) or high dose (KH). In each group, O2 delivery (Do2) was progressively reduced by hemorrhage. At each step, systemic Do2 and O2 consumption (VO2) were measured separately and the critical point was determined from a plot of Vo2 vs. Do2. The critical O2 extraction ratio (OER) in the control group was 65.0 +/- 7.8%. OER was lower in all anesthetized groups (P, 44.3 +/- 11.8%; E, 47.0 +/- 7.7%; HL, 45.7 +/- 11.2%; I, 44.3 +/- 7.1%; HH, 33.7 +/- 6.0%; AL, 56.5 +/- 9.6%; AH, 43.5 +/- 5.9%; KH, 57.7 +/- 7.1%), except in the KL group (78.3 +/- 10.0%). The effects of halothane and alfentanil on critical OER were dose dependent (P less than 0.05), whereas critical OER was significantly lower in the KH than in the KL group. Moreover, the effects of anesthetic agents on critical Do2 appeared related to their effects on systemic vascular resistance. Anesthetic agents therefore alter O2 extraction by their peripheral vascular effects. However, ketamine, with its unique sympathetic stimulant properties, had a lesser effect on OER than the other anesthetic agents. It could therefore be the anesthetic agent of choice in clinical situations when O2 availability is reduced.


2019 ◽  
Vol 50 (6) ◽  
Author(s):  
Ali & et al.

 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.


2007 ◽  
Vol 21 (4) ◽  
pp. 439-443 ◽  
Author(s):  
Ching-Yin Ho ◽  
Ching-Ting Tan

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.


Author(s):  
M. K. Patel ◽  
D. J. Dave ◽  
R. C. Rathod ◽  
B. P. Joshi ◽  
D. J. Ghodasara

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


1993 ◽  
Vol 70 (05) ◽  
pp. 817-821 ◽  
Author(s):  
Jean-P Carteaux ◽  
Beat Steiner ◽  
Sébastien Roux

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.


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 ◽  
...  

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.


2013 ◽  
Vol 448-453 ◽  
pp. 1089-1092 ◽  
Author(s):  
Lan Zhang

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.


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