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Enhancement in antinociceptive and anti-inflammatory effects of tramadol by transdermal proniosome gel

Asian Journal of Pharmaceutical Sciences 2020年第6期15卷 786-796页

作者： Jigar Shah Anroop B.Nair Hiral Shah Shery Jacob Tamer M.Shehata Mohamed Aly Morsy Institute of Pharmacy Nirma UniversityAhmedabad 382481India College of Clinical Pharmacy King Faisal UniversityAl-Ahsa 31982Saudi Arabia Arihant School of Pharmacy&BRI Gandhinagar 382421India College of Pharmacy Gulf Medical UniversityAjman 4184United Arab Emirates Faculty of Pharmacy University of ZagazigZagazig 44519Egypt Faculty of Medicine Minia UniversityEl-Minia 61511Egypt

Oral therapy of tramadol,an opiate analgesic,undergoes extensive hepatic metabolism and requires frequent administration.Transdermal therapy by virtue can overcome these issues and can improve the efficacy and reduce abuse liability of tramadol.The aim of this research was to investigate the possibility of transdermal delivery of tramadol by formulating proniosome gel and evaluate its therapeutic potential in vivo.The effect of formulation composition as well as amount of drug on physicochemical characteristics of prepared proniosomes were examined.Best proniosome gel(F4)was selected and evaluated for drug release,stability and transdermal efficacy by ex vivo and in vivo experiments.The vesicles demonstrated optimal properties including spherical shape,nanosize with good entrapment efficiency,adequate zeta potential,higher stability and greater transdermal flux.The amorphization and dispersion of tramadol in the aqueous core of proniosome vesicles was confirmed by differential scanning calorimeter.Release profile of F4 was distinct(Prats,as compared to oral tramadol.The improvement in clinical efficacy of tramadol in transdermal therapy is correlated with the pharmacokinetic data observed.In conclusion,the observed improvement in antinociceptive and anti-inflammatory effects from proniosome carriers signifies its potential to be a suitable alternative to oral therapy of tramadol with greater efficacy.

关键词： Tramadol Proniosomes Flux Edema Pharmacokinetics rats

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Animal Models and Experimental Medicine 2018年第4期1卷 295-304页

作者： Olaoluwa Sesan Olukiran Rufus Ojo Akomolafe Olutosin Samuel Ilesanmi Christian Eseigbe Imafidon Quadri Kunle Alabi Department of Physiological Sciences Faculty of Basic Medical Sciences Obafemi Awolowo University Department of Biochemistry and Molecular Biology Faculty of Sciences Obafemi Awolowo University Department of Physiology Faculty of Basic Medical and Health Sciences Bowen University

Background: The study determined the fractions of proteins in the urine and plasma of rats at different ages, measured the plasma and urine concentrations of markers of renal function, with a view to determining the influence of proteinuria on renal function.Methods: Eighty Wistar rats were used for this study. Groups 1 and 2 each consisted of eight 1-month-old male and female rats; 3 and 4 had eight 3-month-old male and female rats; 5 and 6 had eight 6-month-old male and female rats; 7 and 8 had eight 9-month old male and female rats; and 9 and 10 had eight 12-month-old male and female rats.Results: A fraction of the molecular weight of protein in the urine of rats aged 1, 9 and 12 months was higher than that of 3 and 6 months. The total protein concentration in the urine of male and female rats aged 9 and 12 months was significantly higher than that of rats aged 1 and 3 months. The urine creatinine concentrations of male and female rats aged 9 months were significantly higher when compared with that of 1, 3, 6 and 12 months.Conclusion: Our results suggest that the 3-month-old rats seem less affected by proteinuria, because they had the least urine protein, and consistent and reduced plasma and urine concentrations of markers of renal function. The results of this study may provide a foundation for future mechanistic inquiries as to why this age group was the least affected by proteinuria.

关键词： creatinine electrophoresis protein rats urea

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Effect of Taoren Quyu Decoction on human endometrial cells and its anti-endometriosis activity in rats

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Asian Pacific Journal of Tropical Medicine 2017年第7期10卷 758-762页

作者： Hai-Zhi Liu Xiao-Xue Han Jia Liu Feng-Cheng Zhu Rui-Man Li Department of Gynaecology and Obstetrics the First Affiliated Hospital of Jinan UniversityGuangzhou 510630Guangdong ProvinceChina

Objective: To study the effect of Taoren Quyu Decoction(TQD) on endometrial cells in patients with endometriosis(EMs) and EMs in rats. Methods: A total of 60 female Wistar rats were randomly divided into 4 groups, namely, normal group, model group, positive group and TQD group, each group having 15 rats. Except the normal group, EMs model was established in the other three groups by transplanting the rat autologous endometrium. After 4 weeks of intragastric administration, blood, eutopic and ectopic endometrial tissues of rats in each group were collected to detect the serum levels of estrogen(E2), cancer antigen 125(CA125), endometrial antibody(EMAb), and expressions of microvessel density(MVD), vascular endothelial growth factor(VEGF) and angiopoietin(Ang-2). The volume of endometriosis cyst was determined simultaneously. For the in vitro culture of human endometrial cells, 4 groups, namely, normal group, model group, positive group and TQD group were used. The positive group and TQD group were treated with danazol and TQD respectively. Then 24 h after the treatment, the expressions of survivin and tumor suppressor gene(p53) of each group were detected. Results: The volumes of the endometriosis cysts in the positive group and the TQD group were significantly reduced compared with the model group(P0.05). Con

关键词： Taoren Quyu Decoction Endometriosis Endometrial cell rats Angiogenesis Apoptosis

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Dry environment on the expression of lacrimal gland S100A9,Anxa1,and Clu in rats via proteomics

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 435-443页

作者： Yi-Lin Sun A-Yuan Cui Li-Xin Wang Wang-Wang Zhang Hong Shi College of Traditional Chinese Medicine Xinjiang Medical UniversityUrumqi 830011Xinjiang Uygur Autonomous RegionChina Research on High Incidence of Diseases in Xinjiang Region Key Laboratory of the Ministry of Education(Xinjiang Medical University)Urumqi 830011Xinjiang Uygur Autonomous RegionChina

●AIM:To investigate the underlying mechanism of dry environment(autumn dryness)affecting the lacrimal glands in rats.●METHODS:Twenty Sprague-Dawley rats were randomly divided into two groups.The rats were fed in specific pathogen free environment as the control group(n=10),and the rats fed in dry environment as the dryness group(n=10).After 24d,lacrimal glands were collected from the rats.The tissues morphology was observed by hematoxylineosin(HE)staining.Tandem mass tags(TMT)quantitative proteomics analysis technology was used to screen the differential expressed proteins of lacrimal glands between the two groups,then bioinformatics analysis was performed.Further,the immunohistochemical(IHC)method was used to verify the target proteins.●RESULTS:In dryness group,the lacrimal glands lobule atrophied,the glandular cavities enlarged,the sparse nuclear distribution and scattered inflammatory infiltration between the acinus were observed.The proteomics exhibited that a total of 195 up-regulated and 236 downregulated differential expressed proteins screened from the lacrimal glands of rats.It was indicated that the biological processes(BP)of differential expressed proteins mainly included cell processes and single BP.The cellular compositions of differential expressed proteins mainly located in cells,organelles.The molecular functions of differential expressed proteins mainly included binding,catalytic activity.Moreover,the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that the differential expressed proteins mainly involved lysosome,complement and coagulation cascade,and ribosome pathway.The IHC result verified that the up-regulated expression proteins of Protein S100A9(S100A9),Annexin A1(Anxa1),and Clusterin(Clu)in lacrimal glands of rats in dryness group were higher than control group.●CONCLUSION:The up-regulated expression proteins of S100A9,Anxa1,and Clu may be the potential mechanisms of dry eye symptoms caused by dry environment.This study provides clues of dry environments causing eye-rel

关键词： dry eye lacrimal gland S100A9 Clu Anxa1 environment rats

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Protective Effects of Estradiol on Myocardial Contractile Function Following Hemorrhagic Shock and Resuscitation in rats

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Chinese Medical Journal 2015年第17期128卷 2360-2364页

作者： Mona Soliman Department of Physiology Colrege of Medicine King Saud University Riyadh 11461 Saudi Arabia

Background： Hemorrhagic shock （HS） results in myocardial contractile dysfunction. Studies showed that 17β-estradiol protects the myocardium against contractile dysfunction. The study investigated the cardioprotective effects of treatment with 17β-estradiol before resuscitation following 1 h of HS and resuscitation. Methods： Male Sprague-Dawley rats were assigned to 2 sets of experimental protocols： Ex vivo and in vivo treatment and resuscitation. Each set had three experimental groups （n = 6 per group）： Normotensive （N）, HS and resuscitation （HS-R） and HS rats treated with 17β-estradiol （E） and resuscitated （HS-E-R）. rats were hemorrhaged over 60-rain to reach a mean arterial blood pressure of 40 mmHg. In the ex vivo group, hearts were resuscitated by perfusion in the Langendorff system. In the 17β-estradiol treated group, 17β-estradiol 280 μg/kg was added for the first 5 min. Cardiac function was measured. Left ventricular generated pressure （LVGP） and ＋dP/dt were calculated. In the in vivo group, rats were treated with 17β-estradiol 280 ±g/kg s.c. after 60-rain HS. Resuscitation was performed in vivo by the reinfusion of the shed blood for 30-min to restore normotension. Results： Treatment with 17β-estradiol before resuscitation in ex vivo treated and resuscitated isolated hearts and in the in vivo treated and resuscitated rats following HS improved myocardial contractile function. In the in vivo treated group, LVGP and ＋dP/dt max were significantly higher in 17β-estradiol treated rats compared to the untreated group （LVGP 136.40 ± 6.61 compared to 47.58 ± 17.55, and ＋dP/dt 661.85 ± 49.88 compared to 88.18 ± 0.85）. Treatment with 17β-estradiol improved LVGP following HS. Conclusions： The results indicate that treatment with 17β-estradiol before resuscitation following HS protects the myocardium against dysfunction.

关键词： Contractility Heart Hemorrhage rats Resuscitation

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Functional electrical stimulation-facilitated proliferation and regeneration of neural precursor cells in the brains of rats with cerebral infarction

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Neural Regeneration Research 2014年第3期9卷 243-251页

作者： Yun Xiang Huihua Liu Tiebin Yan Zhiqiang Zhuang Dongmei Jin Yuan Peng Department of Rehabilitation Medicine Sun Yat-sen Memorial Hospital Sun Yat-sen University Department of Rehabilitation Medicine Shenzhen Sixth People’s Hospital Department of Rehabilitation Medicine Guangzhou First People’s Hospital

Previous studies have shown that proliferation of endogenous neural precursor cells cannot alone compensate for the damage to neurons and axons. From the perspective of neural plastici- ty, we observed the effects of functional electrical stimulation treatment on endogenous neural precursor cell proliferation and expression of basic fibroblast growth factor and epidermal growth factor in the rat brain on the infarct side. Functional electrical stimulation was performed in rat models of acute middle cerebral artery occlusion. Simultaneously, we set up a placebo stimulation group and a sham-operated group. Immunohistochemical staining showed that, at 7 and 14 days, compared with the placebo group, the numbers of nestin （a neural precursor cell marker）-positive cells in the subgranular zone and subventricular zone were increased in the functional electrical stimulation treatment group. Western blot assays and reverse-transcription PCR showed that total protein levels and gene expression of epidermal growth factor and basic fibroblast growth factor were also upregulated on the infarct side. Prehensile traction test results showed that, at 14 days, prehension function of rats in the functional electrical stimulation group was significantly better than in the placebo group. These results suggest that functional electrical stimulation can promote endogenous neural precursor cell proliferation in the brains of acute cerebral infarction rats, enhance expression of basic fibroblast growth factor and epidermal growth factor, and improve the motor function of rats.

关键词： nerve regeneration brain injury functional electrical stimulation neural precursor cells neurogenesis basic fibroblast growth factor epidermal growth factor nestin stroke rats NSFC grant neural regeneration

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Potential targets for protecting against hippocampal cell apoptosis after transient cerebral ischemiareperfusion injury in aged rats

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Neural Regeneration Research 2014年第11期9卷 1122-1128页

作者： Xiangyu Ji Li'na Zhang Ran Liu Yingzhi Liu Jianfang Song He Dong Yanfang Jia Zangong Zhou Department of Anesthesiology Affiliated Hospital of Qingdao University Department of Anesthesiology Qingdao Municipal Hospital Department of General Surgery Affiliated Hospital of Qingdao University

Mitochondria play an important role in neuronal apoptosis caused by cerebral ischemia, and the role is mediated by the expression of mitochondrial proteins. This study investigated the involvement of mitochondrial proteins in hippocampal cell apoptosis after transient cerebral ischemia-reperfusion injury in aged rats using a comparative proteomics strategy. Our exper-imental results show that the aged rat brain is sensitive to ischemia-reperfusion injury and that transient ischemia led to cell apoptosis in the hippocampus and changes in memory and cognition of aged rats. Differential proteomics analysis suggested that this phenomenon may be mediated by mitochondrial proteins associated with energy metabolism and apoptosis in aged rats. This study provides potential drug targets for the treatment of transient cerebral isch-emia-reperfusion injury.

关键词： nerve regeneration cerebral ischemia reperfusion injury hippocampus cognitivefunction apoptosis mitochondria differential proteomics rats aged neural regeneration

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Pulmonary Immune Responses to Aspergillus Fumigatus in rats

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Biomedical and Environmental Sciences 2014年第9期27卷 684-694页

作者： MIRKOV Ivana EL-MUZGHI Amal Atia Mhfuod DJOKIC Jelena NINKOV Marina POPOV ALEKSANDROV Aleksandra GLAMOCLIJA Jasmina KATARANOVSKI Milena Department of Ecology Institute for Biological Research ‘Sinisa Stankovic'University of Belgrade Department of Plant Physiology (Mycology Lab) Institute for Biological Research ‘Sinisa Stankovic'University of Belgrade Institute of Physiology and Biochemistry Faculty of BiologyUniversity of Belgrade

Objective To evaluate immunologic mechanisms underlying Aspergillus fumigatus pulmonary infections in immunocompetent Dark Agouti （DA） and Albino Oxford （AO） rats recognized as being susceptible to some inflammatory diseases in different manners. Methods Lung fungal burden （quantitative colony forming units, CFU, assay）, leukocyte infiltration （histology, cell composition） and their function （phagocytosis, oxidative activity, CDllb adhesion molecule expression） and cytokine interferon-y （IFN-y） and interleukin-17 and -4 （IL-17 and IL-4） lung content were evaluated following infection （intratracheally, lxl07 conidia）. Results Slower reduction of fungal burden was observed in AO rats in comparison with that in DA rats, which was coincided with less intense histologically evident lung cell infiltration and leukocyte recovery as well as lower level of most of the their activities including intracellular myeloperoxidase activity, the capacity of nitroblue tetrazolium salt reduction and CDllb adhesion molecule expression （except for phagocytosis of conidia） in these rats. Differential patterns of changes in proinflammatory cytokine levels （unchanged levels of IFN-v and transient increase of IL-17 in AO rats vs continuous increase of both cytokines in DA rats） and unchanged levels of IL-4 were observed. Conclusion Genetically-based differences in the pattern of antifungal lung leukocyte activities and cytokine milieu, associated with differential efficiency of fungal elimination might be useful in the future use of rat models in studies of pulmonary aspergillosis.

关键词： A. fumigatus rats Lung immune responses

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Iloprost inhibits fracture repair in rats

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Chinese Medical Journal 2014年第16期127卷 2960-2965页

作者： Ali Dogan Fatih Duygun A. Murat Kalender Irfan Bayram Ibrahim Sungur Department of Orthopedics and Traumatology Education andResearch HospitalAntalya Turkey Department of Orthopedics and Traumatology Sutcu ImamUniversity School of Medicine Kahramanmaras Turkey Department of Pathology Yuzuncu Yil University School ofMedicine Van Turkey Department of Orthopedics and Traumatology Haseki Education and Research Hospital Istanbul Turkey

Background Previous studies have shown that prostaglandins （PGs） dramatically stimulate healing processes in bone.However,the effect of prostaglandin l2 （PGI2） on fracture healing remains unclear.To investigate the effect of PGI2,a study on fracture healing process in closed tibia fractures was designed.Methods Thirty-six Sprague-Dawley male rats were randomized into two groups.On the first day,their right tibias were fractured by three-point bending technique.The study group （n=18） received a single injection of 10 μg/kg iloprost for 5 days,while the control group （n=18） received saline solution in the same way.On the 7th,14th and 28th days following the fracture,six rats were sacrificed and their right legs were harvested in each group.The progression of fracture healing was assessed for each specimen by the scores of radiography （by Lane-Sandhu） and histology （by Huo et al）.Results On the 7th day,the radiographic and histologic scores were equal.On the 14th day radiographic total score was 6 and histologic total score was 23 in the iloprost group,whereas radiographic total score was 11 and histologic total score was 33 in the control group.On the 14th day radiographic and histologic scores were significantly decreased in the iloprost group compared to the control group （P 〈0.05）.On the 28th day radiographic total score was 12 and histologic total score was 37 in the iloprost group,whereas radiographic total score was 15 and histologic total score was 40 in the control group.On the 28th day although there was a decrease in radiographic and histologic scores of the iloprost group acording to control group,it was not statistically significant （P 〉0.05）.Conclusion Iloprost delays fracture healing in early stage in rats.

关键词： epoprostenol iloprost fracture healing bone rats prostaglandin I2

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Effect of moxibustion on survival status and nutritional metabolic factor in tumor-bearing rats with gastric cancer

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World Journal of Acupuncture-Moxibustion 2019年第3期29卷 210-215页

作者：彭卓隽谭静陈欲攀赵欢石峻林林亚平湖南中医药大学针灸推拿学院长沙410208 湖南中医药大学中医学国内一流建设学科长沙410208

Objective:To observe the effect of moxibustion on the survival status and nutritional metabolic factors of tumor-bearing rats with gastric cancer and explore the inhibitory effect of moxibustion on the tumorbearing rats.Methods:A total of 40 SD rats were randomly divided into a blank group,a sham-operated group,a model group and a moxibustion group,10 rats in each group.Gastric cancer models were established in the model group and the moxibustion group.The rats of all the groups underwent the same constraining procedure for 20 min every day.Additionally,moxibustion was applied at acupoints for 20 min in the rats of the moxibustion group.There were two groups of acupoints.One group included"Zusanli(足三里ST 36)""Zhongwan(中脘CV12)"and"Guanyuan(关元CV4)".The other group included bilateral"Pishu(脾俞BL 20)"and"Weishu(胃俞BL 21)".Moxibustion was applied for 20 min every day at the acupoints of the two groups alternatively and lasted for 14 days.The survival status of rats was observed and the score of survival status and body weight of rats were recorded every day.At the end of intervention,the orbital blood was collected and the rats were sacrificed for sample collection.The viscera-free body weight was recorded.Using biochemical analyzer,the blood glucose(GLU),albumin(ALB),total protein(TP)and triglyceride(TG)in serum were detected.Results:(1)Regarding the score of the survival status,after modeling,the scores in the model group and the moxibustion group were all higher than those of the sham-operation group(both P<0.05).After intervention,the score in the moxibustion group was lower than that of the model group(P<0.05).(2)After modeling,the body weight in the moxibustion group and the model group was lower than those of the blank group,indicating a statistical significance(both P<0.05).The body weight in the moxibustion group was higher than that of the model group after intervention,indicating the statistical significance(P<0.05).(3)Regarding the viscera-free body weight,it was lower in the model group compared with the sha

关键词： Moxibustion Tumor-bearing rats with gastric cancer Survival status Blood glucose(GLU) Albumin(ALB) Total protein(TP) Triglyceride(TG) Viscera-free weight

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