scholarly journals Doxorubicin triggers splenic contraction and irreversible dysregulation of COX and LOX that alters the inflammation-resolution program in the myocardium

2018 ◽  
Vol 315 (5) ◽  
pp. H1091-H1100 ◽  
Author(s):  
Jeevan Kumar Jadapalli ◽  
Griffin W. Wright ◽  
Vasundhara Kain ◽  
Mohammad Asif Sherwani ◽  
Ravi Sonkar ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Structural Changes ◽  
Low Dose ◽  
Chronic Phase ◽  
Saline Control ◽  
Control Group ◽  
High Dose ◽  
Saline Control Group ◽  
Inflammation Resolution ◽  
Acute And Chronic Exposure

Doxorubicin (DOX) is a widely used drug for cancer treatment as a chemotherapeutic agent. However, the cellular and integrative mechanism of DOX-induced immunometabolism is unclear. Two-month-old male C57BL/6J mice were divided into high- and low-dose DOX-treated groups with a maintained saline control group. The first group was injected with a high dose of DOX (H-DOX; 15 mg·kg−1·wk−1), and the second group was injected with 7.5 mg·kg−1·wk−1 as a latent low dose of DOX (LL-DOX). H-DOX treatment led to complete mortality in 2 wk and 70% survival in the LL-DOX group compared with the saline control group. Therefore, an additional group of mice was injected with an acute high dose of DOX (AH-DOX) and euthanized at 24 h to compare with LL-DOX and saline control groups. The LL-DOX and AH-DOX groups showed obvious apoptosis and dysfunctional and structural changes in cardiac tissue. Splenic contraction was evident in AH-DOX- and LL-DOX-treated mice, indicating the systems-wide impact of DOX on integrative organs of the spleen, which is essential for cardiac homeostasis and repair. DOX dysregulated splenic-enriched immune-sensitive lipoxygenase and cyclooxygenase in the spleen and left ventricle compared with the saline control group. As a result, lipoxygenase-dependent D- and E-series resolvin precursors, such as 16HDoHE, 4HDoHE, and 12-HEPE, as well as cyclooxygenase-mediated PG species (PGD2, PGE2, and 6-keto-PG2α) were decreased in the left ventricle, suggestive of defective immunometabolism. Both AH-DOX and LL-DOX induced splenic contraction and expansion of red pulp with decreased CD169+ metallophilic macrophages. AH-DOX intoxicated macrophages in the spleen by depleting CD169+ cells in the acute setting and sustained the splenic macrophage loss in the chronic phase in the LL-DOX group. Thus, DOX triggers a vicious cycle of splenocardiac cachexia to facilitate defective immunometabolism and irreversible macrophage toxicity and thereby impaired the inflammation-resolution program. NEW & NOTEWORTHY Doxorubicin (DOX) triggered splenic mass loss and decreased CD169 with germinal center contraction in acute and chronic exposure. Cardiac toxicity of DOX is marked with dysregulation of immunometabolism and thereby impaired resolution of inflammation. DOX suppressed physiological levels of cytokines and chemokines with signs of splenocardiac cachexia.

Antitumor Activity of Porcine Cartilage Polysaccharide on Breast Cancer

2013 ◽  
Vol 716 ◽  
pp. 451-454
Author(s):  
Jing Jing Fang ◽  
An Jun Liu ◽  
Zhen Yuan Zhu ◽  
An Guo Teng ◽  
Guo Qiang Zheng ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Animal Models ◽  
Antitumor Activity ◽  
Normal Saline ◽  
Antitumor Effect ◽  
Saline Control ◽  
Control Group ◽  
High Dose ◽  
Saline Control Group ◽  
Tumor Bearing

The antitumor activity of porcine cartilage polysaccharide was evaluated by vivo animal models. The Ca761 tumor-bearing mice were treated with daily intraperitoneal injections of normal saline (control group) or cartilage polysaccharide (1500, 3000 or 4500mg/kg CPS group) for 14 days. The results demonstrated that CPS could effectively inhibit the tumor growth in Ca761 tumor-bearing mice. The tumor weights of the CPS groups were smaller compared to the control group. While the thymus index, spleen index were higher in the high dose 4500mg/kg CPS group than the control group. These results suggest that CPS might be a strong natural immunomodulator and the antitumor effect of this polysaccharide is associated with its potent immunostimulating effect.

Acetaminophen: Neonatal hepatotoxicity due to late pregnancy exposure

1987 ◽  
Vol 45 ◽  
pp. 718-719
Author(s):  
G.A. Miranda ◽  
M.A. Arroyo ◽  
C.A. Lucio ◽  
M. Mongeotti ◽  
S.S. Poolsawat
Keyword(s):  
Low Dose ◽  
Fetal Liver ◽  
Late Pregnancy ◽  
Toxic Chemicals ◽  
Control Group ◽  
High Dose ◽  
Over The Counter ◽  
Liver And Kidney ◽  
Neonatal Liver ◽  
Childbearing Women

Exposure to drugs and toxic chemicals, during late pregnancy, is a common occurrence in childbearing women. Some studies have reported that more than 90% of pregnant women use at least 1 prescription; of this, 60% used more than one. Another study indicated that 80% of the consumed drugs were not prescribed, and of this figure, 95% were “over-the-counter” drugs. Acetaminophen, the safest of all over-the-counter drugs, has been reported to induce fetal liver necrosis in man and animals and to have abortifacient and embryocidal action in mice. This study examines the degree to which acetaminophen affects the neonatal liver and kidney, when a fatty diet is simultaneously fed to the mother during late pregnancy.Timed Swiss Webster female mice were gavaged during late pregnancy (days 16-19) with fat suspended acetaminophen at a high dose, HD = 84.50 mg/kg, and a low dose, LD = 42.25 mg/kg; a control group received fat alone.

scholarly journals Low-dose sublingual immunotherapy compared to subcutaneous immunotherapy and conventional therapy in childhood asthma

2016 ◽  
Vol 44 (6) ◽  
pp. 243
Author(s):  
Ariyanto Harsono
Keyword(s):  
Childhood Asthma ◽  
Low Dose ◽  
Sublingual Immunotherapy ◽  
Disease Onset ◽  
Ethics Committee ◽  
Subcutaneous Immunotherapy ◽  
Control Group ◽  
High Dose ◽  
Treat Ment ◽  
Group A

Background Evidence begin to accumulate that high-dose sub-lingual immunotherapy (SLIT) is as effective as subcutaneousimmunotherapy (SIT) in the treatment of childhood asthma.Since the capacity of sublingual area is similar whether the doseis high or low, the efficacy of low dose may be important to bestudied.Objective To investigate the efficacy of low-dose sublingual im-munotherapy in the treatment of childhood asthma.Methods Parents signed informed consent prior to enrollment,after having received information about the study. Patients weremoderate asthma aged 6-14 years with disease onset of lessthan 2 years before the commencement of the study and peakexpiratory flow rate (PEFR) variability of more than 15%. Pa-tients were randomly allocated into group A, B, and C whoreceived subcutaneous immunotherapy, low-dose sublingualimmunotherapy, and conventional asthma therapy, respectively.Randomization was stratified into two strata according to agei.e., 6-11 years or 11-14 years. Patients of each stratum wererandomized in block of three for each group. At the end of threemonths, lung function tests were repeated. The primary outcomewas PEFR variability at the end of the study. The study wasapproved by the Ethics Committee of Soetomo HospitalSurabaya.Results Distribution of variants as represented by sex, age,eosinophil count, and total IgE concentration were normal inthe three groups. PEFR variability decreased significantly from16.97+0.81 to 8.50+5.08 and 17.0+0.87 to 8.40+4.72 in groupreceiving SIT and SLIT, respectively (p<0.05), but decreasednot significantly from 17.00+0.83 to 10.82+0.5.41 in control group(p>0.05).Conclusion Low-dose SLIT is as efficacious as SIT in the treat-ment of moderate asthma in children

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

scholarly journals SUBCHRONIC TOXICITY TEST OF COMBINATION ETHANOL EXTRACT OF DETAM 1 SOYBEAN (GLYCINE MAX L. MERR) AND JATI BELANDA (GUAZUMA ULMIFOLIA LAMK) TOWARD FUNCTION, WEIGHT, AND HISTOPATHOLOGICAL OF WISTAR RAT LIVER

2016 ◽  
Vol 9 (5) ◽  
pp. 197
Author(s):  
Meilinah Hidayat ◽  
Sijani Prahastuti ◽  
Estherolita Dewi ◽  
Dewi Safitri ◽  
Siti Farah Rahmawati ◽  
...  
Keyword(s):  
Liver Function ◽  
Toxicity Test ◽  
Low Dose ◽  
Ethanol Extract ◽  
Good Effect ◽  
Control Group ◽  
High Dose ◽  
Subchronic Toxicity ◽  
Treatment Groups ◽  
Significant Difference

ABSTRACTObjective: As an antiobesity therapy, combination extracts of Detam 1 soybean and Jati Belanda will be consumed for a long time; therefore, theirtoxicities to the liver need to be investigated. To determine the effect of subchronic toxicity test of combination of ethanol extract of Detam 1 soybean(EEDS) and ethanol extract of Jati Belanda (EEJB) on liver function with parameters: Alanine transaminase (ALT), macroscopic, and histopathologicalof liver.Methods: This study was conducted on 120 Wistar rats (60 males and 60 females), 90 days (treatment group) and 120 days (satellite group). Ratswere divided into six treatment groups (3 test materials, 1 control, and 2 satellites); each group included 10 males and 10 females.Results: ALT levels of treatment groups (low dose, medium, and high), both males and females were lower than the control group (p<0.05). Thetreatment groups demonstrated a good effects effect on liver function. Liver weight of all groups showed no significant difference compared with thecontrol group (p>0.05). Results of histopathological score interpretation of male and female liver rats of low dose groups were not disturbed; middledose groups were slightly disturbed and high dose groups were damaged. Satellite high doses of male groups were disrupted, while female groupswere not.Conclusion: The combination of EEDS and EEJB has a good effect on liver function, did not lead to change organ weight and at low doses did not causerenal histopathology damage in rats after 90 days administration.Keywords: Combination of soybean Jati Belanda, Toxicity subchronic test, Function, Weight, Histopathology, Liver.

scholarly journals Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Pure Water ◽  
Intervention Group ◽  
Control Group ◽  
High Dose ◽  
Endocrine Glands ◽  
Blood Samples ◽  
High Doses ◽  
The Brain

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).

Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers

1987 ◽  
Vol 17 (4) ◽  
pp. 869-873 ◽  
Author(s):  
C. Schmauss ◽  
J.-C. Krieg
Keyword(s):  
Low Dose ◽  
Matched Control ◽  
Control Group ◽  
High Dose ◽  
Withdrawal Therapy ◽  
The Mean ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Age And Sex

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.

Addition of Epinephrine to Intrathecal Bupivacaine and Sufentanil for Ambulatory Labor Analgesia

1997 ◽  
Vol 86 (3) ◽  
pp. 525-531 ◽  
Author(s):  
David C. Campbell ◽  
Robert Banner ◽  
Lesley-Ann Crone ◽  
Wendy Gore-Hickman ◽  
Ray W. Yip
Keyword(s):  
Labor Analgesia ◽  
Saline Control ◽  
Control Group ◽  
Double Blind Study ◽  
Saline Control Group ◽  
Double Blind ◽  
Prolonged Labor ◽  
Intrathecal Analgesia ◽  
Limited Duration ◽  
Effective Analgesia

Background The intrathecal combination of sufentanil and bupivacaine provides rapid, effective analgesia for labor with a limited duration. Many anesthesiologists have concerns that the use of intrathecal local anesthetics precludes maternal ambulation. This prospective, randomized, double-blind study was designed to determine whether the addition of epinephrine to the combination of sufentanil and bupivacaine would prolong intrathecal analgesia for labor. Patients' ability to ambulate was also assessed. Methods Thirty-nine patients received either an intrathecal control dose of 10 micrograms sufentanil plus 2.5 mg bupivacaine plus 0.2 ml normal saline (control group); or 10 micrograms sufentanil plus 2.5 mg bupivacaine plus 0.2 ml (0.2 mg) of epinephrine (EPI group). Results Seven patients (3 control, 4 EPI) delivered vaginally and two (1 control, 1 EPI) required cesarean delivery before requesting epidural analgesia. The duration (mean +/- SD) of intrathecal labor analgesia was prolonged significantly by the addition of epinephrine: control (n = 15): 145 +/- 23 min; EPI (n = 15): 188 +/- 25 min (P &lt; 0.0001). Maternal ambulation was demonstrated in 100% (19 of 19) of the control group and in 80% (16 of 20) of the EPI group (P = NS). Conclusions The addition of 0.2 mg epinephrine to the intrathecal combination of sufentanil and bupivacaine significantly prolonged labor analgesia without causing adverse effects to the mother or fetus. The intrathecal combination of sufentanil and bupivacaine, with or without epinephrine, provided rapid, profound labor analgesia and allowed most patients to ambulate.

scholarly journals Gengnianchun Recipe Protects Ovarian Reserve of Rats Treated by 4-Vinylcyclohexene Diepoxide via the AKT Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Fangui Zhao ◽  
Wenjun Wang
Keyword(s):  
Ovarian Reserve ◽  
Low Dose ◽  
Control Group ◽  
High Dose ◽  
Model Group ◽  
Menopausal Syndrome ◽  
Primordial Follicles ◽  
Akt Phosphorylation ◽  
Vinylcyclohexene Diepoxide ◽  
Sd Rats

Diminished ovarian reserve (DOR) refers to a decrease in the number and quality of oocytes. Western treatment of DOR does not improve the ovarian reserve fundamentally, and the effect is limited. Gengnianchun recipe (GNC) is a traditional Chinese medicine formula originally applied to treat menopausal syndrome but is also found to be effective in treating clinical DOR patients. Here we aim to examine the effect of GNC in a DOR rat model induced by 4-vinylcyclohexene diepoxide (VCD), a chemical that selectively destroys ovarian small preantral follicles, and further investigate the possible mechanisms. Female SD rats were randomly divided into four groups: control group (C), model group (M), high-dose GNC group (H), and low-dose GNC group (L). Rats in M, H, and L were administered with VCD and normal saline, high-dose GNC, and low-dose GNC separately. Rat ovaries were harvested either to conduct HE staining for follicle count, immunohistochemistry, or western blot. We found that high dose of GNC significantly increased the ovarian index and sustained the number of primordial follicles and primary follicles in VCD treated rats. Moreover, high dose of GNC significantly increased the ovarian protein expression of mouse vasa homologue (MVH), anti-Müllerian hormone (AMH), follicle-stimulating hormone receptor (FSHR), and estrogen receptor β (ERβ) compared with that in the model group. Besides, high-dose GNC significantly increased ovarian AKT phosphorylation and the expression of downstream forkhead box O3 (FOXO3a). Proapoptosis proteins of Bax, cleaved caspase-3, and poly ADP-ribose polymerase (PARP) were significantly decreased after high-dose GNC treatment compared with those in the model group. Taken together, these findings suggest that high-dose GNC could protect ovarian reserve against VCD-induced toxicity via the activation of the AKT signaling pathway and reduced cell apoptosis in SD Rats. This effect could either be induced by the increased FSHR signaling or by the nontranscriptional activation of ERβ, which requires further investigation.

scholarly journals Effect of Astragalus membranaceus Oral Solution on Lifespan and Learning and Memory Ability of Honey Bees

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Tao Hong ◽  
Long-Xue Li ◽  
Xiao-ping Han ◽  
Jing-liang Shi ◽  
Cai-yun Dan ◽  
...  
Keyword(s):  
Learning And Memory ◽  
Honey Bees ◽  
Dose Group ◽  
Low Dose ◽  
Oral Solution ◽  
Astragalus Membranaceus ◽  
Control Group ◽  
High Dose ◽  
The Mean ◽  
And Control

In this study, the effects of Astragalus membranaceus oral solution on lifespan and learning and memory abilities of honey bees were evaluated. Two groups of bees were fed with sucrose syrup (50%) containing low dose (1.33%) and high dose (13.3%) of A. membranaceus oral solution, respectively. The proboscis extension response (PER) analysis was applied to examine the learning and memory capabilities of bees. Two genes related to memory formation in honey bees were determined by real-time PCR. High dose (13.3%) of A. membranaceus significantly decreased the mean lifespan of bees compared to the bees fed with low dose (1.33%) and control bees. No significant differences in lifespan of bees were found between low-dose-fed bees and control bees. The results of PER experiments showed apparent improvement in the memorizing ability of the high-dose group (in comparison with the control group). Moreover, the relative expression levels of Nmdar1 in the low-dose group and control group were significantly lower than those in the high-dose group. It is preliminarily concluded that A. membranaceus has an adverse effect on the mean lifespan of honey bees but might be helpful in strengthening memories.

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