scholarly journals GASTROPROTECTIVE ACTIVITY OF SESAME (SESAMUM INDICUM) SEEDS EXTRACT IN ALENDRONATE-INDUCED GASTRIC ULCER IN RATS

2019 ◽  
pp. 214-217
Author(s):  
SHUBANGEE MISHRA ◽  
BALAJI O ◽  
VANISHREE RAO ◽  
SHALINI ADIGA
Keyword(s):  
Gastric Ulcer ◽  
Wistar Rats ◽  
Sesame Seed ◽  
Saline Group ◽  
Gastric Ulcers ◽  
Peptic Ulcers ◽  
Protective Effects ◽  
Gastroprotective Activity ◽  
Group 5 ◽  
Group 2

Objectives: Bisphosphonates are known to cause gastritis and only few studies have evaluated the use of plant extracts in the treatment of bisphosphonate induced peptic ulcers. In the present study, we examined the effect of sesame seed extract in the alendronate-induced gastric ulcer in adult Wistar rats. Methods: Thirty adult Wistar rats (180–250 g) of both sexes, divided into five groups (n=6) were used: Group 1 (vehicle control) – 0.9% saline, Group 2 (ulcer control) – alendronate 60 mg/kg, Group 3 (standard) – alendronate 60 mg/kg + pantoprazole 30 mg/kg/day, Group 4 (test groups) – alendronate 60 mg/kg + sesame 0.5 mg/kg, and Group 5 (test groups) – alendronate 60 mg/kg + sesame 1 mg/kg. All drugs were given orally once daily for 7 days except for alendronate given only on day 1. On day 8, rats were sacrificed, and stomach tissues were analyzed macroscopically for ulcers. Estimation of gastric pH, acidity, and volume was done along with mucin content measurement. One-way ANOVA followed by Tukey’s post hoc test was used for statistical analysis with p<0.05 taken as significant. Results: Our study found that sesame extract given therapeutically at doses of 0.5 and 1 mg/kg showed comparable results with that of pantoprazole 30 mg/kg. Both the doses of sesame, 0.5 and 1 mg/kg showed similar gastroprotective activity against alendronate-induced gastric ulcers in Wistar rats. Conclusion: The findings of this study clearly demonstrated the protective effects of Sesame against alendronate-induced gastric ulceration.

scholarly journals Protective effect of zinc and Pine barks extract supplement against Indometacin-induced gastric ulcer in rats

2021 ◽  
Vol 8 (1) ◽  
pp. 1-14
Author(s):  
Derouiche Samir ◽  
Kaouachi Aicha
Keyword(s):  
Gastric Ulcer ◽  
Pinus Halepensis ◽  
Antioxidant Properties ◽  
Saline Group ◽  
Bark Extract ◽  
Control Group ◽  
Group 4 ◽  
Single Oral Administration ◽  
Group 5 ◽  
Group 2

Abstract This investigation was aimed to study the effect of Pinus halepensis aqueous bark extract and zinc to prevent indomethacin induced gastric ulcer in rats. Thirty female albino Wistar rats were divided into 6 groups of 5 animals each (n=5); Group 1: normal control, Group 2: ulcer rats received normal saline, Group 3: ulcer rats treated with P. halepensis, Group 4: ulcer rats were treated with zinc, Group 5: ulcer rats were treated with P. halepensis + zinc and Group 6 ulcer rats were treated with Ranitidine for 15 days. Stomach ulcer was induced by a single oral administration of indomethacin (30 mg/kg). Various biochimical, physiologic and histologic parameters were estimated. Obtained results show that the ulcer index, pH and total acidity level were significantly reduced (p<0.05) and Pepsin activity was significantly increased (p< 0.05) in ulcer induced rats pre-treated with extract of P. halepensis, zinc and ranitidine when compared with indomethacin treated rats. The MDA level was significantly decreased and GSH level was increased (p< 0.05) in rats treated with plant extract and zinc. Histopathology of gastric mucosa confirmed the gastro-protection by plant and zinc treatment. The study reveals anti-ulcer and antioxidant properties were observed in bark aqueous extract of P. halepensis groups with a benefic effect of zinc to reduce oxidative stress and gastric ulcer induced in the rat.

scholarly journals Kidney ischemia and reperfunsion syndrome: effect of lidocaine and local postconditioning

2016 ◽  
Vol 43 (5) ◽  
pp. 348-353 ◽  
Author(s):  
IGOR NAGAI YAMAKI ◽  
RUY VICTOR SIMÕES PONTES ◽  
FELIPE LOBATO DA SILVA COSTA ◽  
VITOR NAGAI YAMAKI ◽  
RENAN KLEBER COSTA TEIXEIRA ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Serum Levels ◽  
Saline Group ◽  
Renal Ischemia ◽  
Ischemic Postconditioning ◽  
Control Group ◽  
Ischemia And Reperfusion ◽  
Lidocaine Group ◽  
Group 5 ◽  
Group 2

ABSTRACT Objective: to evaluate the effects of blocking the regulation of vascular tone on the ischemia and reperfusion syndrome in rats through the use of lidocaine in the postconditioning technique. Methods: we randomized 35 rats into seven groups of five animals: Group 1- Control; Group 2- Ischemia and Reperfusion; Group 3- Ischemia, Reperfusion and Saline; Group 4- Ischemic Postconditioning; Group 5- Ischemic Postconditioning and Saline; Group 6- Lidocaine; Group 7- Ischemic Postconditioning and Lidocaine. Except for the control group, all the others were submitted to renal ischemia for 30 minutes. In postconditioning groups, we performed ischemia and reperfusion cycles of five minutes each, applied right after the main ischemia. In saline and lidocaine groups, we instilled the substances at a rate of two drops per minute. To compare the groups, we measured serum levels of urea and creatinine and also held renal histopathology. Results: The postconditioning and postconditioning + lidocaine groups showed a decrease in urea and creatinine values. The lidocaine group showed only a reduction in creatinine values. In histopathology, only the groups submitted to ischemic postconditioning had decreased degree of tubular necrosis. Conclusion: Lidocaine did not block the effects of postconditioning on renal ischemia reperfusion syndrome, and conferred better glomerular protection when applied in conjunction with ischemic postconditioning.

scholarly journals Attenuated Leishmania major Induce a High Level of Protec-tion against Leishmania infantum in BALB/c Mice

2019 ◽  
Author(s):  
Shamsi NOORPISHEH GHADIMI ◽  
Leila HOMAYOON ◽  
Reza SHAHRIARIRAD ◽  
Shakila FATEHPOUR ◽  
Mohammad RASTEGARIAN ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Parasite Load ◽  
Major Group ◽  
Protective Effects ◽  
Medical Sciences ◽  
Intensity Of Infection ◽  
Group 4 ◽  
Group 5 ◽  
Group 2 ◽  
High Level

Background: The current study aimed to investigate the possible cross-protective effects of attenuated L. major against L. infantum in BALB/c mice. Methods: This experimental study was performed in 2017 in Shiraz University of Medical Sciences, Shiraz, Iran. The attenuated strain of L. major was prepared by continuous weekly subculturing of the parasite. Forty-eight female BALB/c mice were divided into eight groups. Group 1 injected (ID) with wild type of L. major; group 2 injected (IV) with L. infantum; group 3 injected (ID) with attenuated L. major; group 4 injected (ID) with attenuated L. major, and after three weeks challenged (IV) with L. infantum; group 5 injected (IP) with attenuated L. major; group 6 injected (IP) with attenuated L. major, and challenged (IV) with L. infantum (IV); group 7 injected (IV) with attenuated L. major; and finally group 8 injected (IV) with attenuated L. major and after three weeks challenged (IV) with L. infantum. Forty-five days post-infection, the parasite load in the spleen and liver of the mice was determined as Leishman-Donovan units (LDU). Results: The differences in mean of LDU of spleen between different groups were statistically significant (P<0.048). In addition, the differences in percent of infection in liver between pairwise comparisons of groups were statistically significant (P<0.05). The highest intensity of infection was observed in group 2 while low intensity of infection was seen in groups 3, 4 and 5. Conclusion: Live attenuated L. major can induce substantial protection against L. infantum, particularly when the parasites were injected intravenously.

scholarly journals Hepatic Enzyme Effects of an Imperata cylindrica Extract

2021 ◽  
pp. 32-40
Author(s):  
M. O. Nwokike ◽  
S. I. Ghasi ◽  
E. C. Ogbuagu ◽  
M. N. Ezenwaeze ◽  
Akpotu E. Ajirioghene
Keyword(s):  
Wistar Rats ◽  
Intraperitoneal Administration ◽  
Ethanol Extract ◽  
Diabetic Rats ◽  
Imperata Cylindrica ◽  
Root Extract ◽  
Hepatic Enzyme ◽  
Male Wistar Rats ◽  
Group 5 ◽  
Group 2

This study was performed to investigate the effects of aqueous Imperata cylindrica root extract on hepatic enzyme levels of alloxan-induced diabetic male Wistar rats. Forty (48) male wistar rats were divided into six groups consisting of eight animals each. Diabetes mellitus was induced using intraperitoneal administration 150 mg/kg body weight of alloxan and treatment was carried out for a period of 28 days. The first group served as the normal control and received only feed and water ad libitum. In Group 2 were diabetic rats without treatment with extracts. Group 3: diabetic rats treated with 200 mg/kg aqueous Imperata cylindrica root extract. Group 4: diabetic rats treated with 400mg/kg aqueous Imperata cylindrica root extract. Group 5: diabetic rats treated with 600mg/kg ethanol extract of aqueous Imperata cylindrica root extract. While Group 6 was diabetic rats treated with 0.5mg/kg Glibenclamide. The liver enzymes alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels were significantly (p < 0.05) changed in rats treated with Alloxan (150mg/kg b.w.) while treatment with the respective dosages of extracts significantly changed the levels of these parameters to normal. The results obtained indicate that the different doses of aqueous Imperata cylindrica root extracts were beneficial in mending damages to the liver caused by Alloxan monohydrate in the male wistar rats.

scholarly journals Pengaruh Kecepatan Pembentukan Tukak Lambung Terhadap Pemberian Berbagai Golongan NSAID Pada Tikus Jantan

2019 ◽  
Vol 1 (2) ◽  
pp. 8-17
Author(s):  
Parhan Parhan ◽  
Aliman Yafarugi Gulo
Keyword(s):  
Gastric Ulcer ◽  
Diclofenac Sodium ◽  
Gastric Ulcers ◽  
Dominant Factor ◽  
Epithelial Tissue ◽  
Peptic Ulcers ◽  
Epithelial Layer ◽  
Gastrointestinal Mucosa ◽  
Mucosal Layer ◽  
The Difference

Background : Gastric ulcer is wound to the mucosal layer (epithelial layer) of the stomach and mucosal irritation of 5 mm or more in diameter with depth down to submucosa. The basic pathogenesis of gastric ulcers in when there is an imbalance of aggressive factor enhancement. Non-steroidal antiinflammantory drug can cause stomach ulcers in two ways, either directly or topical irritation of the epithelial tissue and inhibit the endogeneous system of gastrointestinal mucosa of prostaglandins. In this case inhibition of prostaglandin systhesis is the dominant factor of peptic ulcers by NSAIDs. Objectives : The purpose of this study was to determine the effct of NSAID drug administration on the formation of peptic ulcers and to know the difference in the rate of formation of peptic ulcers from each class. Method : Sampel method mice performed surgery on the stomach is done in Pharmacology Laboratory of Pharmacy Institute Deli Husada Deli Tua. Results : The results of this study indicate that faster drugs cause gastric ulcers with a degree of redness are Aspirin 4.03 mm, 2.01 mm mefenamat and 1.02 mm Diclofenac Sodium while Ibuprofen mwdication does not cause peptic ulcers. Conclusion : The results of this study it can be concluded that Aspirin administration with doses of 21 mg/kg faster causes gastric ulcers from other NSAID groups such as Mefenamat with a dose of 21 mg/kg BW, Diclofenac sodium at a dose of 2 mg/kg while administration, Ibuprofen for ten days does not couse ulcers in the stomach of experimetal animals.

Hepatoprotective effect of chewable tablet of Centella asiatica (L.) Urb extractin Wistar rats induced by high fat diets

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Akrom ◽  
Feri Anggita Hastanto ◽  
Laela hayu Nurani
Keyword(s):  
Wistar Rats ◽  
Serum Triglyceride ◽  
Centella Asiatica ◽  
High Fat ◽  
Chewable Tablet ◽  
High Fat Diets ◽  
Group 3 ◽  
Group 5 ◽  
Group 2 ◽  
Fat Diets

Gotukola or Centella asiatica (L.) Urban contains high flavonoids which well known as fatty liver protector. This study aimed to evaluate the hepatoprotective effect of chewable tablet of C. asiatica (L.) Urb extract (CTCE) in Wistar rats induced by high fat diets. Twenty-one Wistar male rats aged 8-12 weeks with body weight ranging from 100-150 g were used in this study. Rats were randomly divided into seven groups i.e. Group 1 as normal control, rats were given standard food, Group 2 as high fat diets control, rats were induced high fat diets (HFD),Group 3 as positive control, rats were induced HFD and given simvastatin, Group 4 as placebo control, rats were induced HFD and given placebo, Group 5-7 as treatment group, rats were induced HFD and given CTCE at doses of 100, 200 and 300 mg/kg BW, respectively. The HFD induction was conducted for five weeks andthe CTCE was given for one week in the last week of the induction. At the end of the intervention, blood triglyceride levels and SGPT as well SGOT activities were examined. Analysis of variance (ANOVA) with confidence interval of 95% (p<0.05) was applied. The results showed that the HFD induction increased the serum triglyceride levels and SGPT activity. The serum triglyceride levels and SGPT activity of Group 2 were significantly higher than Group 1 (p<0.05). Furthermore, the simvastatin and CTCE administration reduced the serum triglyceride levels and SGPT activity. The serum triglyceride levels and SGPT activity of Group 3, 5, 6and 7 were significantly lower than Group 2 and 4 (p<0.05). In addition, the serum triglyceride levels and SGPT activity of Group 5, 6 and 7 were significantly lower than Group 3 (p<0.05). In conclusion, CTCE can reduce the serum triglyceride levels and SGPT activity in Wistar rats induced by HFD.

Toxicity of bean cooking media containing EDTA in mice

2020 ◽  
Vol 36 (6) ◽  
pp. 436-445
Author(s):  
Sabry Ali El-Naggar ◽  
Karim Samy El-Said ◽  
Mona Elwan ◽  
Maysa Mobasher ◽  
Fotouh Mansour ◽  
...  
Keyword(s):  
Ethylenediaminetetraacetic Acid ◽  
White Blood Cells ◽  
Saline Group ◽  
Negative Control ◽  
Blood Levels ◽  
Group 4 ◽  
Liver And Kidney ◽  
Group 5 ◽  
Group 2 ◽  
Kidney Functions

The possible renal and hepatic toxicities of ethylenediaminetetraacetic acid (EDTA) in bean cooking media were studied using 100 male albino mice. Two sublethal doses of EDTA were used to explore their toxic effects; 20 mg/kg and 200 mg/kg, which corresponded to 1/100th and 1/10th of LD50, respectively. Accordingly, the toxicity study was performed using 50 mice, divided into five groups ( n = 10/group) as follows: group 1 (Gp1) served as a negative control and was orally administered normal saline; group 2 (Gp2) was administered the bean cooking medium; group 3 (Gp3) was administered EDTA (200 mg/kg); group 4 (Gp4) was administered bean cooking medium containing 20 mg/kg of EDTA; and group 5 (Gp5) was administered bean cooking medium containing 200 mg/kg of EDTA. The results showed no significant changes in liver and kidney functions in Gp2 while Gp3, Gp4, and Gp5 exhibited significant increases in adverse liver and kidney function markers. Hematocrit values were significantly decreased in Gp3 and Gp5, while the total white blood cells counts were significantly decreased in Gp3 and significantly increased in Gp5. The number of platelets was decreased in Gp3, Gp4, and Gp5. The blood levels of sodium (Na+), iron (Fe2+), and calcium (Ca2+) were decreased in Gp3, Gp4, and Gp5 due to the chelating effects of EDTA. The hepatic and renal architectures were disorganized in Gp3, Gp4, and Gp5 with some hemorrhagic manifestations in livers and kidneys of mice. These results demonstrate that EDTA in bean cooking is harmful in mice under the conditions of this study, and the potentially harmful effects in humans supports restricting its use.

scholarly journals Anti-Inflammatory and Antioxidative Potential of Aloe vera on the Cartap and Malathion Mediated Toxicity in Wistar Rats

2020 ◽  
Vol 17 (14) ◽  
pp. 5177 ◽  
Author(s):  
Vivek Kumar Gupta ◽  
Abhishek Kumar ◽  
Maria de Lourdes Pereira ◽  
Nikhat Jamal Siddiqi ◽  
Bechan Sharma
Keyword(s):  
Aqueous Extract ◽  
Wistar Rats ◽  
Biological Effects ◽  
Aloe Vera ◽  
Control Group ◽  
Alternative Agent ◽  
Group 5 ◽  
Pre Treatment ◽  
Group 2 ◽  
Histopathological Results

Aloe vera has been the most useful medicinal herb in the world since ancient times due to its vast biological effects. The presence of high content of bioactive compounds make Aloe vera a promising complementary and alternative agent in disease prevention. The effectiveness of A. vera-based medicines against pesticide toxicity has never been evaluated. It was therefore envisaged to develop an A. vera-based strategy to protect the non-target animals from adverse effects of the pesticides. This article illustrates the ameliorating effect of aqueous extract (AE) of A. vera leaves against the cartap and malathion toxicity. To evaluate the protective impact of A. vera against cartap (Ctp), malathion (Mtn) and a mixture of both pesticides, the animals were divided in eight groups, each containing six rats: Group 1- C (control), Group 2- AE + C, Group 3- Ctp, Group 4- Mtn, Group 5- Ctp + Mtn, Group 6- AE + Ctp, Group 7- AE + Mtn, Group 8- AE + Ctp + Mtn. Wistar rats exposed to Ctp, Mtn and Ctp + Mtn, displayed significant change in body weight. It was observed that the WBC level increased significantly in Mtn and Ctp + Mtn challenged groups. The contents of TNF-α and IL-6 in serum increased expressively in the Ctp, Mtn and Ctp + Mtn challenged groups. Rats treated with Ctp, Mtn and Ctp + Mtn displayed significant alterations in the levels of antioxidative indices (MDA, GSH, GST, GPx, SOD and CAT). Significant alterations were recorded in the activities of AST, ALT, ACP and ALP in Ctp, Mtn and Ctp + Mtn challenged groups. The histopathological results of liver supported the biochemical data. The pre-treatment of rats with the aqueous extract of A. vera leaves significantly protected them from the toxicity of pesticides. These results suggested that A. vera extract may be used as a promising natural agent for the management of pesticide induced toxicity.

scholarly journals Calliandra portoricensis ameliorates ovarian and uterine oxido-inflammatory responses in N-methyl-N-nitrosourea and benzo[a]pyrene-treated rats

2020 ◽  
Vol 245 (16) ◽  
pp. 1490-1503 ◽  
Author(s):  
Adedoyin O Adefisan ◽  
Judith C Madu ◽  
Solomon E Owumi ◽  
Oluwatosin A Adaramoye
Keyword(s):  
Inflammatory Responses ◽  
Control Group ◽  
Root Bark ◽  
Protective Effects ◽  
Weight Changes ◽  
Chemopreventive Agents ◽  
Toxic Response ◽  
Analgesic Effects ◽  
Group 5 ◽  
Group 2

Reproductive dysfunction stemming from chemical agents may lead to infertility. We examined the protective effects of Calliandra portoricensis ( CP) extract on benzo[a]pyrene (BaP) and N-methyl- N-nitrosourea (NMU)-induced ovarian and uterine toxicity in rat, treated as follows: control (group 1), NMU + BaP (group 2), groups 3 and 4 received (NMU + BaP), and CP (50 and 100 mg/kg), respectively. Group 5: CP (100 mg/kg) alone, group 6: (NMU + BaP) and vincristine (VIN: 0.5 mg/kg) and group 7: VIN alone. Rats were injected at age 7, 10, and 13 weeks with single doses of NMU and BaP for 10 consecutive weeks. NMU + BaP significantly ( P < 0.05) increased ovarian and uterine weight, and decreased bodyweight, while the organo-somatic index (OSI) of uterus and ovary increased 2.3 and 1.4 folds, respectively. CP co-treatment ameliorated the observed weight changes. Lipid peroxidation increased by 58% in the ovary, accompanied by decreases in ovarian and uterine GST, GPx, catalase activities, and total sulfhydryl level in NMU + BaP-treated rats. Uterine and ovarian myeloperoxidase activities, as well as nitric oxide levels also increased. CP co-treatment ameliorated the observed changes in antioxidant enzymes and inflammatory biomarkers. Furthermore, histopathology revealed fibrotic ovarian stroma, while uterine endometrium was infiltrated with inflamed cells. Immunohistochemistry showed weak expression of FSH, LH, p53, caspase-3, and Bax, whereas progesterone, iNOS, and Bcl-2 were strongly expressed in NMU + BaP-treated rats. CP treatment restored the architecture of these tissues. Conclusively, the root bark fraction of CP decreases oxido-inflammatory damage in ovarian and uterine tissues of NMU- and BaP-treated rats. Impact statement Infertility resulting from reproductive impairment is traumatic in families. Exposure to chemicals may play insidious roles not easily connected to infertility. We examined benzo[a]pyrene (BaP), and N-methyl nitrosourea (NMU)-induced ovarian and uterine toxicity and the role of Calliandra portoricensis in mitigating toxicity. In a bid to illuminate folk medical claims cloaked in mystery, unearthing lost knowledge, advance natural chemopreventive agents, and report new evidence lacking in the literature attributed to CP. Although CP is known to exhibit anticonvulsant, antidiarrheal, antipyretic, antirheumatic, and analgesic effects in humans, its possible roles for mitigating toxicity stemming from inadvertent chemical exposures are reported here. Our findings affirm and further show that CP abates toxic response incumbent on oxidative damage and inflammatory responses associated with NMU and BaP exposure. Development of phytochemical derived from CP may serve as a potential natural therapy against chemical toxicities in individuals inadvertently exposed, and promote human health and reproductive satiety.

Protective mechanisms of protocatechuic acid against doxorubicin-induced nephrotoxicity in rat model

2019 ◽  
Vol 30 (4) ◽  
Author(s):  
Olorunfemi R. Molehin ◽  
Anne A. Adeyanju ◽  
Stephen A. Adefegha ◽  
Ajibade O. Oyeyemi ◽  
Kehinde A. Idowu
Keyword(s):  
Body Weight ◽  
Protocatechuic Acid ◽  
Serum Levels ◽  
Protective Effects ◽  
Glutathione S Transferase ◽  
Protective Mechanisms ◽  
Malondialdehyde Content ◽  
Group 5 ◽  
Group 2 ◽  
Inducible Nitric Oxide

AbstractBackgroundDoxorubicin (DOX) induces toxicity in many tissues/organs, including the heart, kidney and so on. This study was designed to evaluate the modulatory effects of protocatechuic acid (PCA) against DOX-induced nephrotoxicity in rats. Animals were randomly grouped into five groups.MethodsGroup 1 served as the normal control (CTR). A single dose of DOX at 20 mg/kg was administered intraperitoneally (i.p.) to animals in Group 2. Groups 3 and 4 were pretreated with PCA for 5 days (doses of 10 and 20 mg/kg body weight, respectively) after which DOX was injected (PCA-10 + DOX and PCA-20 + DOX). Group 5 received PCA only at a dose of 20 mg/kg body weight (PCA-20).ResultsThe results revealed significant elevations (p < 0.05) in malondialdehyde content, expressions of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX2) in the kidney. Likewise, increased serum levels of creatinine and urea of DOX group were observed. A significant decrease (p < 0.05) in glutathione (GSH) level and antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione s- transferase (GST) activities in the kidney were observed compared with the control. Pretreatment with PCA (10 and 20 mg/kg, p.o.) for 5 days prior to the i.p. injection of DOX reduced MDA levels, modulated iNOS and COX2 activities and improved kidney function markers as well as oxidative stress parameters. Findings from the histopathology studies confirms the protective effects of PCA on DOX-induced damage on the kidney cells.ConclusionsThis study has demonstrated the anti-inflammatory and antioxidative properties of PCA, which could be part of its possible protective mechanisms against nephrotoxicity induced by DOX.

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