scholarly journals S207. CHRONIC TREATMENT WITH 1METIQ INDUCES PRO-COGNITIVE EFFECT ON RECOGNITION MEMORY IN KETAMINE MODEL OF SCHIZOPHRENIA IN RATS

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S117-S117
Author(s):  
Magdalena Białoń ◽  
Agnieszka Wąsik ◽  
Marcelina Żarnowska

Abstract Background Schizophrenia is severe mental disorder that affects 1% of world population and cause long-term disability (Mueser and McGurk, 2004). Manifestation of the illness can be distinguished into three groups – positive, negative and cognitive symptoms (van Os, 2009). However, cognitive ones (e.g. memory deficits) seem to remain resistant to pharmacotherapy (Cerveri et al., 2019). Memory deficits, as a symptoms of schizophrenia, may be modeled in animals by using a specified dose of ketamine and measured in novel object recognition (NOR) test (Lafionatis et al., 2019). 1-methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous amine present and synthesized in the mammalian brain with neuroprotective properties (Antkiewicz-Michaluk et al., 2014) and our last study have shown anxiolytic action of 1MeTIQ in rat model of schizophrenia (Wąsik et al., 2019) therefore we decided to define a potential of 1MeTIQ to exhibit pro-cognitive effect on memory in ketamine-treated rats. Methods NOR test consisted of adaptation (24h before testing) and two phases (T1 and T2, with 1-hour interval). Exploration times of each objects, preference (PI) and discrimination (DI) indexes were measured. Microdialysis was performed to asses glutamate release in frontal cortex. Male Sprague Dawley rats were divided into 4 groups. The control group received saline injections. Animals received acute ketamine (20mg/kg, i.p.) or chronic (7x) administration of1MeTIQ (50mg/kg, i.p.). The combined group received single dose of ketamine 30 minutes after last dose of 1MeTIQ. Results In T1 phase of NOR, there were no changes between exploration times of two identical objects. In T2 phase with two different objects, we observed no significant changes in group treated with ketamine. 1MeTIQ given alone increased the difference between time of objects exploration. In combined group, 1MeTIQ completely reversed the effect of ketamine. Ketamine tended, however, without statistical significance, to decrease PI and DI. Treatment with 1MeTIQ did not change mentioned indexes. In microdialysis study, we observed no significant changes in glutamate release in any group. Discussion We demonstrated that chronic administration of 1MeTIQ may improve recognition memory function. However, we didn’t observe changes in glutamate release. We suggest that pro-cognitive effect of 1MeTIQ is associated with its impact on monoamine metabolism.

2020 ◽  
Vol 86 (8) ◽  
pp. 1038-1042
Author(s):  
Hannah M. Nemec ◽  
Hany Atalah ◽  
Melissa Kling ◽  
Larry Nichols ◽  
Bowen Powers ◽  
...  

Background Adhesions are bands of tissue that form postoperatively after intra-abdominal surgery. Adhesions cause significant morbidity and despite ongoing research no agent or method has been shown to completely prevent adhesions. Human amnion-derived matrix is a complex tissue matrix derived from human placenta and has been used in other areas of surgery to promote healing and decrease scar tissue formation. Our hypothesis was that aerosolized human amnion-derived matrix particulate solution (HAMPS) applied during abdominal surgery would decrease adhesion formation in rats. Methods Twenty-four Sprague-Dawley rats were divided into 4 different groups. Group 1 was the control group (CG) which had cecal abrasion 20× with a surgical rasp to generate the adhesion model. Groups 2-4 were the treatment groups (TGs) and had cecal abrasion plus application of the HAMPS at concentrations of 6.25, 12.5, and 25 mg/cc, respectively. After 30 days, rats were euthanized and adhesion assessment performed. Results In all groups there were minimal adhesions noted at necropsy. Moderate inflammation was 33% in CG versus 11% in combined TGs. Average adhesion was 1.00 in CG versus 0.44 in combined TGs. This indicated an observational improvement in adhesions/inflammation in the TGs, although this did not reach statistical significance. There was a trend toward significance in the 12.5 mg/cc group alone ( P = .054). Conclusion Overall, HAMPS showed an observational decrease in adhesions in TGs although not statistically significant. There was a trend toward significance in the 12.5 mg group. Additional studies will have to be performed to further evaluate this subgroup.


2019 ◽  
Vol 22 (5) ◽  
pp. 326-332
Author(s):  
Sarah Shin ◽  
No Soo Kim ◽  
Young Ah Kim ◽  
Hea Ry Oh ◽  
Ok-Sun Bang

Background: Traditionally, Phragmitis rhizoma has been prescribed to relive a fever, vomiting, dysuria, and constipation, and to promote secretion of fluids. In addition, recent studies have reported its efficacy as a diuretic and antiemetic. Our previous study demonstrated that the Phragmitis rhizoma aqueous extract (EPR) ameliorates docetaxel (DTX)-induced myelotoxicity. Aim and Objective: This study was aimed to investigate the effects of EPR on the pharmacokinetics of DTX in Sprague–Dawley rats. Materials & Methods: The animals received an intravenous injection of DTX (5 mg/kg) with or without oral EPR (100 mg/kg) pretreatment for 1 or 6 days. The pharmacokinetics of plasma DTX was analyzed using an ultra-performance liquid chromatography-tandem mass spectrometry system, and pharmacokinetic parameters were estimated via noncompartmental analysis. Results: Relative to the control group (DTX alone), EPR pretreatment did not affect significantly the overall profiles of plasma DTX levels. Consecutively pretreated EPR for 6 days slightly altered AUC0-t and Cmax of DTX by 122 and 145.9%, respectively, but these data did not reach the threshold of statistical significance (p > 0.05). Conclusion: These results indicate that DTX exposure may not be affected by EPR treatment at the dose level used in this study, suggesting that oral EPR can be used safely when taken with intravenously injected DTX. However, further studies under the stringent conditions are needed when chronic treatment of EPR and anticancer drug.


Author(s):  
Azrina Zainal Abidin ◽  
Nurain Syahirah Rosli ◽  
Santhra Segaran ◽  
Azmiza Syawani Jasni ◽  
Hasnah Bahari

Abstract Objectives Pre-pregnancy obesity is a serious epidemics concern that negatively affects the neurodevelopmental of the offspring. Elateriospermum tapos (E. tapos) commonly used to enhance weight loss in obesity treatment. This study was aimed to investigate the influence of E. tapos supplement in obese maternal prior pregnancy on the offspring’s bodyweight, lipid metabolism and memory function. Methods Thirty female Sprague Dawley rats were used. Six rats were assigned to the normal diet group (DND). The remaining rats were fed with a high-fat and cafeteria diet (HFCD) to generate obesity for 5 weeks. Obese rats were further divided into four groups: Negative Control (DNC; HFCD), Positive Control (DPC; Orlistat 200 mg/kg), treatment 1 (DTX1; E. tapos seed 200 mg/kg) and treatment 2 (DTX2, E. tapos shell 200 mg/kg) were given daily, for 6 weeks prior to mating. At weaning, offspring of both genders were designated into six groups according to their dam’s group (n=6/group). All groups were fed with a cafeteria diet except for the control group. Memory tasks for object and place recognition were conducted on offspring at eighth weeks of age. The offspring were cull at the 12th week of age for their blood sample. Results Both offspring genders from DTX2 significantly reduce bodyweight, calorie intake and triglyceride level. In memory tasks, offspring from DTX2 showed a significant increase in exploration rate in place test as compared to offspring from the DNC group. Conclusions This study highlights E. tapos shell as an anti-obesity agent and protecting memory deficit in obese dam’s offspring.


2019 ◽  
Vol 15 (1) ◽  
pp. e23-29
Author(s):  
Bang-Sub Lee ◽  
Jooyoung Kim ◽  
Wi-Young So

Background and Objective AMP-activated protein kinase (AMPK) functions as a sensor of the intracellular energy status that can be stimulated by a synthetic activator, 5-aminoimidazole–4–carboxamide–1–beta–D–ribofuranoside (AICAR), which is used to replicate the effect of physical exercise in hepatocyte embryoid bodies. This study investigated the effect of AICAR on the CYP3A1 mRNA expression in primary hepatocyte embryoid bodies derived from a rat liver. Material and Methods The primary hepatocytes were isolated from a male Sprague Dawley (SD) rat (215 g) and subjected to the following treatments: control without AICAR (CTL, n=3), 1 μM AICAR (n=3), 10 μM AICAR (n=3), and 100 μM AICAR (n=3). RNA was isolated and used as the template for synthesizing cDNA by reverse transcriptase to perform quantitative PCR (qPCR). The independent samples t-test was conducted to examine differences between groups. Statistical significance was set at p<0.05. Results The qPCR analysis demonstrated that CYP3A1 mRNA expression in primary hepatocyte embryoid bodies significantly increased in the presence of 10 μM (t=1.730, p<0.05) and 100 μM AICAR (t=3.207, p<0.05) as compared to that in the control group hepatocytes. However, the observed increase of CYP3A1 mRNA in hepatocyte embryoid bodies was not statistically significant in the presence of 1 μM AICAR as the lowest test concentration. Conclusion In this study, we demonstrated that AICAR, an AMPK activator, can increase the expression of CYP3A1 mRNA in primary hepatocytes. Future studies should assess the effect of AICAR treatment on CYP3A4 in human hepatocytes.


2020 ◽  
Vol 16 (3) ◽  
pp. 333-342 ◽  
Author(s):  
Wan M.H.W. Yaacob ◽  
Idris Long ◽  
Rahimah Zakaria ◽  
Zahiruddin Othman

Background: Tualang honey (TH) has been shown to exert beneficial effects on learning and memory function in various animal models. However, its learning and memory effects in lipopolysaccharide (LPS) rat model have not been elucidated. Objective: The present study aimed to investigate the cognitive-enhancing effects of TH and its methanolic fraction in comparison to the clinically approved N-methyl-D-aspartate (NMDA) receptor antagonist (memantine) using LPS rat model. Methods: A total of ninety male Sprague Dawley rats were divided into 5 groups: (i) control, (ii) untreated LPS (iii) LPS treated with 200 mg/kg TH, (iv) LPS treated with 150 mg/kg methanol fraction of TH (MTH) and (v) LPS treated with 10 mg/kg memantine. All treatments were administered intraperitoneally once daily for 14 days. Morris water maze (MWM) and novel object recognition (NOR) tests were performed to assess spatial and recognition memory function. Results: The present study confirmed that LPS significantly impairs spatial and recognition memory and alone treatment with TH or MTH improved spatial and recognition memory comparable to memantine. Conclusion: Both TH and its methanolic fraction improved spatial and recognition memory of LPS rat model comparable to memantine. Thus, TH and its methanolic fraction have potential preventivetherapeutic effects for neurodegenerative diseases involving neuroinflammation.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3693 ◽  
Author(s):  
Junli Jiang ◽  
Bin Wang ◽  
Zhaoqiong Zhu ◽  
Jun Yang ◽  
Jin Liu ◽  
...  

Background Because etomidate induces prolonged adrenal suppression, even following a single bolus, its use as an infused anesthetic is limited. Our previous study indicated that a single administration of the novel etomidate analog methoxyethyletomidate hydrochloride (ET-26-HCl) shows little suppression of adrenocortical function. The aims of the present study were to (1) determine the minimum infusion rate of ET-26-HCl and compare it with those for etomidate and cyclopropyl-methoxycarbonylmetomidate (CPMM), a rapidly metabolized etomidate analog that is currently in clinical trials and (2) to evaluate adrenocortical function after a continuous infusion of ET-26-HCl as part of a broader study investigating whether this etomidate analog is suitable for long infusion in the maintenance of anesthesia. Method The up-and-down method was used to determine the minimum infusion rates for ET-26-HCl, etomidate and CPMM. Sprague-Dawley rats (n = 32) were then randomly divided into four groups: etomidate, ET-26-HCl, CPMM, and vehicle control. Rats in each group were infused for 60 min with one of the drugs at its predetermined minimum infusion rate. Blood samples were drawn initially and then every 30 min after drug infusion to determine the adrenocorticotropic hormone-stimulated concentration of serum corticosterone as a measure of adrenocortical function. Results The minimum infusion rates for etomidate, ET-26-HCl and CPMM were 0.29, 0.62, and 0.95 mg/kg/min, respectively. Compared with controls, etomidate decreased serum corticosterone, as expected, whereas serum corticosterone concentrations following infusion with the etomidate analogs ET-26-HCl or CPMM were not significantly different from those in the control group. Conclusion The corticosterone concentrations tended to be reduced for the first hour following ET-26-HCl infusion (as compared to vehicle infusion); however, this reduction did not reach statistical significance. Thus, further studies are warranted examining the practicability of using ET-26-HCl as an infused anesthetic.


Author(s):  
Arthur J. Wasserman ◽  
Azam Rizvi ◽  
George Zazanis ◽  
Frederick H. Silver

In cases of peripheral nerve damage the gap between proximal and distal stumps can be closed by suturing the ends together, using a nerve graft, or by nerve tubulization. Suturing allows regeneration but does not prevent formation of painful neuromas which adhere to adjacent tissues. Autografts are not reported to be as good as tubulization and require a second surgical site with additional risks and complications. Tubulization involves implanting a nerve guide tube that will provide a stable environment for axon proliferation while simultaneously preventing formation of fibrous scar tissue. Supplementing tubes with a collagen gel or collagen plus extracellular matrix factors is reported to increase axon proliferation when compared to controls. But there is no information regarding the use of collagen fibers to guide nerve cell migration through a tube. This communication reports ultrastructural observations on rat sciatic nerve regeneration through a silicone nerve stent containing crosslinked collagen fibers.Collagen fibers were prepared as described previously. The fibers were threaded through a silicone tube to form a central plug. One cm segments of sciatic nerve were excised from Sprague Dawley rats. A control group of rats received a silicone tube implant without collagen while an experimental group received the silicone tube containing a collagen fiber plug. At 4 and 6 weeks postoperatively, the implants were removed and fixed in 2.5% glutaraldehyde buffered by 0.1 M cacodylate containing 1.5 mM CaCl2 and balanced by 0.1 M sucrose. The explants were post-fixed in 1% OSO4, block stained in 1% uranyl acetate, dehydrated and embedded in Epon. Axons were counted on montages prepared at a total magnification of 1700x. Montages were viewed through a dissecting microscope. Thin sections were sampled from the proximal, middle and distal regions of regenerating sciatic plugs.


2013 ◽  
Author(s):  
Gurinder S. Bains ◽  
Lee Berk ◽  
Noha Daher ◽  
Pooja Deshpande ◽  
Everett Lohman ◽  
...  

2020 ◽  
Vol 29 (2) ◽  
pp. 175-179
Author(s):  
Melania Macarie ◽  
Simona Bataga ◽  
Simona Mocan ◽  
Monica Pantea ◽  
Razvan Opaschi ◽  
...  

Background and Aims: The importance of sessile serrated lesions (SSLs) in the pathogenesis of colorectal carcinoma has been recently established. These are supposed to cause the so-called “interval cancer”, having a rapidly progressive growth and being difficult to detect and to obtain an endoscopic complete resection. We aimed to establish the most important metabolic risk factors for sessile serrated lesions. Methods: We performed a retrospective case-control study, on a series of 2918 consecutive patients who underwent colonoscopy in Gastroenterology and Endoscopy Unit, County Clinical Emergency Hospital, Târgu-Mureș, Romania between 1 st of January 2015-31 th of December 2017. In order to evaluate the metabolic risk factors for polyps’ development, enrolled participants were stratified in two groups, a study group, 33 patients with SSLs lesions, and a control group, 138 patients with adenomatous polyps, selected by systematic sampling for age and anatomical site. Independent variables investigated were: gender, smoking, alcohol consumption, obesity, arterial hypertension, diabetes, hypercholesterolemia, hypertriglyceridemia, hyperuricemia, nonalcoholic liver disease. Results: For SSLs the most common encountered localization was the right colon in 30.55% of cases. By comparative bivariate analysis between SSLs group and control group, it was observed that hypertension (p=0.03, OR 2.33, 95 %CI 1.03-5.24), obesity (p=0.03, OR 2.61, 95 %CI 1.08-6.30), hyperuricemia (p=0.04, OR 2.72, 95 %CI 1.28-7.55), high cholesterol (p=0.002, OR 3.42; 95 %CI 1.48-7.87), and high triglycerides level (p=0.0006, OR 5.75; 95 %CI 1.92-17.2) were statistically associated with SSLs development. By multivariate analysis hypertension and hypertriglyceridemia retained statistical significance. Conclusions: Our study showed that the highest prevalence of SSLs was in the right colon and hypertension and increased triglycerides levels were associated with the risk of SSLs development. These risk factors are easy to detect in clinical practice and may help identifying groups with high risk for colorectal cancer, where screening is recommended.


Author(s):  
J.E. Azimova ◽  
E.A. Klimov ◽  
E.A. Naumova ◽  
Z.G. Kokaeva ◽  
A.I. Zaitseva ◽  
...  

Перспективным в изучении биомаркеров мигрени может быть многолокусный анализ, в частности, анализ частот сочетанных генотипов. Цель исследования - поиск составных генетических биомаркеров индивидуальной предрасположенности к мигрени, полученных на основе полиморфизмов генов, уже показавших статистическую значимость при однолокусном ассоциативном анализе. Методика. Обследовано 155 пациентов с мигренью (104 пациента с эпизодической мигренью, 51 - с хронической мигренью), наблюдавшихся в Университетской клинике головной боли (Москва). Все пациенты - представители белой расы, жители Московского региона. Возраст пациентов - 30-50 лет. Контроль составили 365 необследованных лиц (популяционный контроль). Выявление исследуемых 22 генов (всего 31 SNP) осуществляли методом ПЦР, ПЦР-ПДРФ, аллель-специфичной ПЦР и ПЦР в реальном времени. Выявление ассоциированных с мигренью сочетанных генотипов проводили с использованием программы анализа полигенных данных APSampler v3.6. Результаты. Выявлено 8 сочетанных генотипов с высокой статистически значимой ассоциацией с мигренью (ОШ>20,0). В состав сочетанных генотипов вошли гены: CCKAR, CCKBR, COMT, MTHFR, MTR, MTRR. Так же выявлено 4 защитных сочетанных генотипа (ОШ<0,02), основным в которых является ген MAOA. Заключение. Полученные данные об ассоциированных с мигренью сочетанных генотипах указывают на значимую роль в патогенезе заболевания 2 биохимических систем: 1) холецистокининергической системы, регулирующей выброс и обратный захват дофамина, и 2) фолатного цикла, в ходе работы которого гомоцистеин метаболизируется в метионин. Результаты, полученные в данном исследовании, позволяют говорить о защитной роли аллеля VNT:R4 гена MAOA.Multilocus analysis, specifically, analysis of combined genotype frequencies may be promising in studying migraine biomarkers. The aim of the study was to search for composite genetic biomarkers, which would predict individual predisposition to migraine, obtained on the basis of gene polymorphisms that have already shown a statistical significance in a single-locus associative analysis. Methods. 155 patients with migraine aging 41.7 ± 12.5 who had been followed up at the University Clinic of Headache, Moscow, were evaluated (104 patients with episodic migraine and 51 with chronic migraine). All patients were white and residents of the Moscow region. The control group included 365 unexamined individuals (population control). Identification of The 22 genes under study (total, 31 SNPs) were identified by PCR, PCR-RFLP, allele-specific PCR, and real-time PCR. Combined genotypes associated with migraine were identified using the APSampler v3.6 software for polygenic data analysis. Results. Eight combined genotypes were identified with a highly significant association with migraine (OR> 20.0). The combined genotypes included the CCKAR, CCKBR, COMT, MTHFR, MTR, and MTRR genes. Four protective combined genotypes were also identified (OS <0.02) with the MAOA gene as the major one. Conclusion. Our data on migraine-associated combined genotypes indicate a significant role in the migraine pathogenesis of two biochemical systems, i) the cholecystokininergic system that regulates the release and reuptake of dopamine, and ii) the folate cycle, where homocysteine is metabolized to methionine. The results obtained in this study suggest a protective role of the VNT: R4 allele of the MAOA gene.


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