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جستجوی مقالات مرتبط با کلیدواژه « Simvastatin » در نشریات گروه « پزشکی »

  • Mustafa Mert Acikgoz, Ceren Tilgen Yasasever, Necat Vakur Olgac, Erdal Cevher, Gulsum Ak
    Introduction

    Improving bone healing by various methods is one of the research areas of oral and maxillofacial surgery, as in the surgical branches dealing with hard tissue in medicine. Many methods, such as bone grafts, drugs, hormones, and tissue engineering applications, are used in bone reconstruction and rehabilitation. Moreover, improving bone healing is critical for better surgical outcomes. This study aimed to compare early and late period effects of intermittent teriparatide application on bone graft and local simvastatin application from histopathological, histomorphometric analysis, and biochemical aspects.

    Materials and Methods

    24 New Zealand rabbits were divided into four groups. While experimental groups received intermittent teriparatide (30µg/kg), control groups were given sterile distilled water. A total of 3 defects were created on each rabbit’s right and left tibia. Bone graft and local simvastatin were randomly applied to the opened defects, and one defect was left blank for control purposes. Rabbits were sacrificed on days 15 and 30 to examine early and late bone healing. Blood was drawn for biochemical analysis.

    Results

    The healing score and new bone development in teriparatide applied and grafted defects were statistically significant compared to all groups (p<0.05). A statistically significant difference was obtained in grafted defects compared to the control group in teriparatide-applied defects. Local simvastatin caused necrosis in both experimental and control groups. Teriparatide administration does not cause a statistically significant change in calcium, potassium, and parathyroid hormone biomarkers (p>0.05).

    Conclusion

    Better bone healing and bone graft healing in rabbits treated with teriparatide may encourage improved surgical outcomes in clinical practice.

    Keywords: Teriparatide, Intermittent, Bone Healing, Bone Graft, Simvastatin}
  • Hagar B. Abo-Zalam, Ezz El Deen El Denshary, Rania A. Abdalsalam, _ Islam A. Khalil, Mahmoud M. Khattab, Mohamed A. Hamzawy *
    Purpose

     The objective of this study was to develop a nanoencapsulated platform for coenzyme Q10 nanoparticles (coQNPs) or selenium nanoparticles (SeNPs) and explore their potential therapeutic benefits in treating hyperlipidemia and combating simvastatin (SV)-induced myopathy and adverse reactions in hyperlipidemic rats.

    Methods

     The physical and chemical properties of the solid nanoparticles, coQNPs, and SeNPs were characterized, including zeta potential studies. Male Wistar albino rats were treated with various interventions for 112 days, including a nano-vehicle only, high-fat diet (HFD), HFD with SV alone, or with coQNPs or/and SeNPs for the last 30 days.

    Results

     The coQNPs and SeNPs exhibited uniform spherical shapes with high encapsulation efficiency (EE% 91.20±2.14 and 94.89±1.54, respectively). The results demonstrated that coQNPs and SeNPs effectively reduced hyperlipidemia, insulin resistance, SV-induced myopathy, and hepatotoxicity. However, combining SV with coQNPs and SeNPs resulted in severe liver and muscle damage. Treatment with SV and SeNPs or SV and coQNPs alone showed significant improvements compared to SV treatment alone.

    Conclusion

     These findings suggest that the CoQNPs or SeNPs platforms offer advanced relief for hyperlipidemia and insulin resistance while limiting adverse effects such as myopathy and hepatotoxicity.

    Keywords: Coenzyme Q10, Hyperlipidemia, Selenium, Solid Lipid Nanoparticles, Simvastatin}
  • Afarin Aghajari, Mahgol Moaref, Reza Ganji

    Since the prevalence of pressure ulcers has been increasing in recent years, they need a new and efficient treatment. The pleiotropic effects of statins can be used for this purpose. This study aimed to evaluate the appropriate formulation of 3% simvastatin (SIM) topical cream and its effect on the healing of bedsores. At first, the appropriate formulation of SIM topical cream was investigated. In a randomized, double-blind trial, 42 patients were divided into two groups: placebo and SIM cream, and used these creams for three weeks, once every 12 hours on a clean bedsore. Bedsore dimensions were measured at the beginning and end of the study. Seventy-seven percent of patients in the SIM group and 35% in the placebo group had more than 20% healing of bedsores. Age (P=0.03), gender (P=0.01), statin use (P=0.04), and diabetes (P=0.04) had statistically significant impacts on bedsore healing. Also, better wound healing in the non-diabetic patients was observed. It seems that the topical cream of SIM significantly affects the healing of bedsores and can also be used in bedsores of diabetic patients. In diabetic patients with bedsores, blood sugar control through nutritional counseling and consumption of regular diabetic medication seems to be very effective and efficient.

    Keywords: Bedsore, Simvastatin, Statins, Topical, drug, Ulcers, Wound healing}
  • زمینه و هدف

    مصرف بیش از حد غذاهای پرکالری نه تنها باعث چاقی و اختلالات متابولیک می شود، بلکه برخی از فعالیت های سیستم عصبی مانند فرآیندهای شناختی را نیز تحت تاثیر قرار می دهد. مطالعه حاضر با هدف بررسی تاثیر رژیم غذایی کافه تریا از پس از شیرگیری تا نوجوانی بر عملکرد شناختی موش صحرایی انجام شد.

    روش ها

    موش های باردار ویستار از روز زایمان تا 20 روز پس از زایمان با رژیم غذایی طبیعی و آب تغذیه شدند. سپس فرزندان نر به یکی از سه گروه تقسیم شدند: رژیم غذایی کافه تریا(سوسیس، کیک، کوکی کشمشی، هویج، شکلات شیری سفید و شیر کاکایو) (CAF)، رژیم غذایی کافه تریا با سیمواستاتین (CAF-S) و گروه کنترل (CTRL). پس از اتمام درمان ها، عملکرد شناختی موش ها با استفاده از آزمون ماز آبی موریس مورد ارزیابی قرار گرفت.

    یافته ها

    گروه CAF نسبت به دو گروه دیگر کاهش یادگیری را نشان داد و برای یافتن سکوی پنهان در تمام روزهای آزمایش زمان بیشتری طول کشید (0.001 ≥ p). گروه CAF-S که سیمواستاتین را با دوز 50 میلی گرم بر کیلوگرم دریافت کردند، زمان قابل توجهی کوتاه تری برای یافتن پلت فرم پنهان در مقایسه با گروه CAF داشتند (0.05 ≥ p). در طول مرحله یادآوری حافظه پس از برداشتن پلت فرم، گروه CAF-S زمان کمتری را در ربع هدف در مقایسه با گروه های CTRL و CAF-S سپری کرد (0.05 ≥ p).

    نتیجه گیری

    نتایج این مطالعه نشان می دهد که رژیم غذایی کافه تریا منجر به کاهش یادگیری و حافظه بلند مدت در موش ها می شود. این تاثیر احتمالا به دلیل محتوای چربی بالا در رژیم غذایی کافه تریا است. با این حال، سیمواستاتین از این کاهش در موش هایی که از رژیم غذایی کافه تریا تغذیه می کردند جلوگیری کرد. این یافته ها نشان می دهند که مداخلاتی که مسیرهای متابولیک تحت تاثیر رژیم غذایی کافه تریا را هدف قرار می دهند، ممکن است مزایای درمانی بالقوه ای برای اختلالات شناختی داشته باشند.

    کلید واژگان: رژیم غذایی کافه تریا, عملکرد شناختی, یادگیری, حافظه, سیمواستاتین}
    Nilufar Khanjani, Hamid Sepehri*
    Background

    Overconsumption of high-calorie foods not only causes obesity and metabolic disorders but also affects some activities of the nervous system, such as cognitive processes. The present study aimed to investigate the effect of a cafeteria diet from post-weaning to adolescence on the cognitive performance of rats.

    Methods

    Pregnant Wistar rats were fed a normal diet and water from the day of delivery to 20 days postpartum. Male offspring were then assigned to one of 3 groups: a cafeteria diet (sausages, cakes, raisin cookies, carrots, white milk chocolate, and chocolate milk) (CAF), a cafeteria diet with simvastatin (CAF-S), or a control group (CTRL). After the treatments were completed, the cognitive performance of the rats was evaluated using the Morris water maze test.

    Results

    The CAF group showed reduced learning compared to the other two groups, and they took longer to find the hidden platform on all days of the experiment (P ≤ 0.001). The CAF-S group, which received simvastatin at a dose of 50 mg/kg, had a significantly shorter time to find the hidden platform compared to the CAF group (P ≤ 0.05). During the memory recall phase, after removing the platform, the CAF-S group spent less time in the target quadrant compared to the CTRL and CAF-S groups (P ≤ 0.05).

    Conclusion

    The results indicated that the cafeteria diet decreased the rats' learning and long-term memory. This effect is likely due to the high-fat content in the cafeteria diet. However, simvastatin prevented this decrease in the rats fed a cafeteria diet. These findings suggest that interventions targeting the metabolic pathways affected by a cafeteria diet may have potential therapeutic benefits for cognitive disorders.

    Keywords: Diet, Learning, Memory, Simvastatin, Cognitive performance}
  • Maryam Naseroleslami*, Mahdieh Mehrab Mohseni
    Background

    Simvastatin has anti-inflammatory and antioxidant properties against cardiac I/RI. However, it suffers from low bioavailability and a short half-life. Nanoniosomes are novel drug delivery systems that may increase SIM effectiveness. The present research evaluates the impact of SIM-loaded nanoniosomes on the OGD/R injury model of H9c2 cells.

    Methods

    Cells were seeded based on five groups: (1) control; (2) OGD/R; (3) OGD/R receiving SIM; (4) OGD/R receiving nanoniosomes; and (5) OGD/R receiving SIM‑loaded nanoniosomes. OGD/R injury of the H9c2 cells was treated with SIM or SIM‑loaded nanoniosomes. Cell viability, two inflammatory factors, necroptosis factors, along with HMGB1 and Nrf2 gene expressions were assessed.

    Results

    The cells treated with SIM‑loaded nanoniosomes showed a significant elevation in the cell viability and a reduction in HMGB1, Nrf2, TNF-α, IL-1β, RIPK1, and ROCK1 expression levels compared to the OGD/R and SIM groups.

    Conclusion

    Based on our findings, nanoniosomes could safely serve as a drug delivery system to counterbalance the disadvantages of SIM, resulting in improved aqueous solubility and stability.

    Keywords: Necroptosis, Reperfusion injury, Simvastatin}
  • Seyedeh Maryam Mousavi-Simakani, Amir Azadi, Nader Tanideh, Navid Omidifar, Parisa Ghasemiyeh, Soliman Mohammadi-Samani*
    Purpose

     Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, is a commonly used drug to reduce total cholesterol and low-density lipoprotein (LDL) levels. Furthermore, several mechanisms showed the wound-healing potential of statins, especially simvastatin. Simvastatin is a lipophilic drug, therefore, it has low water solubility with limited skin permeability potential. In this regard, nanostructured lipid carriers (NLCs) were recruited as novel topical drug delivery systems to enhance skin adhesion and film formation, maintain skin integrity, sustain the release of simvastatin, and prolong simvastatin skin deposition to help pressure ulcers healing and regeneration.

    Methods

     NLCs were fabricated using the solvent diffusion evaporation technique. Drug loading, in vitro drug release, and morphological assessment on the optimized formulation were considered. Furthermore, in vivo effect of simvastatin-loaded NLCs gel on pressure ulcer healing was assessed using a rat skin model. Histopathological assessments were compared with conventional simvastatin gel and drug-free NLCs gel.

    Results

     Simvastatin-loaded NLC with an average diameter of 100 nm was considered as the optimum formulation. According to the results entrapment efficiency of simvastatin within the NLCs was about 99.4%. Drug release studies revealed sustained drug release from NLCs in which about 87% of the drug was slowly released during 48 hours. Animal study results confirmed that simvastatin-loaded NLCs gel has better efficacy on pressure ulcers and could significantly reduce inflammation, and promote skin regeneration compared to both drug-free NLCs and conventional simvastatin gels.

    Conclusion

     Simvastatin-loaded NLCs with an average particle size of 100 nm would be a promising novel topical drug delivery system with sustained drug release potential for pressure ulcer treatment.

    Keywords: Simvastatin, Nanostructured lipid carriers, Topical drug delivery systems, Histopathological studies, Wound healing}
  • ناهید ابوطالب، مهدیه مهراب محسنی، مریم ناصرالاسلامی *
    زمینه

    ایسکمی قلبی علت اصلی مرگ ومیر بوده و استاتین ها آن را بهبود می بخشند. هدف از این مطالعه افزایش اثربخشی سیمواستاتین نیوزومه شده است.

    روش کار

    تعداد 25 سر موش صحرایی نر نژاد ویستار به 5 گروه کنترل، ایسکمی (القا شده با LAD بسته شده)، ایسکمی قلبی دریافت کننده نیوزوم، ایسکمی قلبی دریافت کننده سیمواستاتین و دریافت کننده سیمواستاتین نیوزومه شده تقسیم شدند. یک ماه پس از تزریق دارو، از بافت قلب گروه های مورد مطالعه، پس از استخراج RNA، cDNA تولید و با استفاده از پرایمرهای اختصاصی آزمون ریل تایم PCR انجام شد. برای تجزیه و تحلیل آماری از نرم افزار SPSS نسخه 21 استفاده شد. برای بررسی تاثیر مداخلات از تحلیل واریانس و سپس از آزمون تعقیبی توکی برای بررسی وجود تفاوت معنادار 0/05>P بین گروه های کنترل، گروه های مداخله و سایر گروه ها استفاده شد.

    یافته ها

    آپوپتوز و اتوفاژی در گروه ایسکمی نسبت به گروه کنترل افزایش معناداری داشت 0/05>P . در گروه سیمواستاتین نیوزومه شده در مقایسه با گروه سیمواستاتین، آپوپتوز و اتوفاژی کاهش معناداری یافتند 0/05>P . همچنین در گروه های سیمواستاتین نیوزومه شده و سیمواستاتین در مقایسه با گروه ایسکمی، آپوپتوز و اتوفاژی کاهش معناداری یافت 0/05>P .

    نتیجه گیری

    سیمواستاتین داروی موثر در بهبود ایسکمی قلبی است اما مشکل اصلی در استفاده از سیمواستاتین ناپایداری و تجزیه پذیری آن است و استفاده از شکل نیوزومه آن این مشکل را حل می کند.

    پیامدهای عملی

    سیمواستاتین نیوزومه شده در مقایسه با سیمواستاتین در کاهش آسیب ایسکمی قلبی موثرتر است.

    کلید واژگان: ریپرفیوژن, سیمواستاتین, نیوزوم, ایسکمی, آپوپتوز, اتوفاژی}
    Nahid Aboutaleb, Mahdieh Mehrab Mohseni, Maryam Naseroleslami *
    Background

    Cardiac ischemia is the major cause of morbidity and mortality which can be increased by Statins. This study aimed to increase the effectiveness of simvastatin in the form of niosomes.

    Methods

    In this study, 25 male Wistar rats were divided into 5 groups: control, ischemia (induced by closed LAD), ischemia receiving nano-niosomes, ischemia receiving simvastatin, and ischemia receiving simvastatin-loaded nano-niosomes. One month after the drug injection, RNA was extracted from the heart tissue of the studied groups, cDNA was synthesized, and a real-time PCR test was performed using specific primers. SPSS 21.0 software was used for statistical analysis. Analysis of variance was used to investigate the effect of the interventions, and Tukey's post hoc test was used to investigate a significant difference (P<0.05) between the control groups and other groups as well as between intervention groups.

    Results

    Apoptosis and autophagy increased significantly in the ischemia group compared to the control group (P<0.05). In the simvastatin-loaded nano-niosomes group, compared to the simvastatin group, apoptosis and autophagy showed a significant decrease (P<0.05), and also in both simvastatin-loaded nano-niosomes and simvastatin group, compared to the control group, apoptosis and autophagy showed a significant decrease. (P<0.05).

    Conclusion

    Simvastatin is an effective drug in the recovery of cardiac ischemia, but the main problem in using simvastatin is its instability and degradability, and the use of its niosomes form solves this problem properly.

    Practical Implications

    Simvastatin‑loaded nano‑niosomes is more effective in reducing heart ischemia damage compared to simvastatin.

    Keywords: Reperfusion, Simvastatin, Niosomes, Ischemia, Apoptosis, Autophagy}
  • مهتاب محمدزاده، احمد اصغری*، شاهین حسن پور
    زمینه و هدف

    هدف اصلی این پژوهش، مطالعه ی اثر سیمواستاتین روی تحمل درد و ارزیابی آنتاگونیست ها به دنبال آسیب عصب سیاتیک در موش صحرایی بود.

    روش کار

    این تحقیق طی 2 مرحله آزمایشی بر روی 85 موش صحرایی نر بالغ و محدوده ی وزنی 180-200 گرم، استفاده شد. تمامی حیوانات قبل از جراحی از نظر سلامت حرکتی ارزیابی شده و سپس تمامی موش ها با تزریق داخل صفاقی داروهای کتامین هیدروکلراید (mg/kg60) و زایلازین (mg/kg10) بیهوش شدند و پس از اسکراب و آماده سازی اولیه پای راست حیوانات، آن ها را به پهلوی چپ حالت گماری کرده و برشی در پوست خلفی-خارجی ناحیه رانی پای چپ داده شد. عضلات و فاسیا را به آرامی کنار زده و پس از در معرض دید قرار گرفتن عصب سیاتیک، با استفاده از هموستات ریز عصب سیاتیک تحت فشار به مدت 60 ثانیه قرار گرفت. به منظور ردیابی، محل آسیب را با بخیه زدن نزدیک ترین عضله به محل له شدگی با استفاده از نخ بخیه (0-5) سیلک غیرقابل جذب نشانه گذاری کرده و سپس عضلات را کنار هم گذاشته و بافت زیرجلد و پوست به ترتیب با استفاده از نخ ویکریل (0-4) و نایلون (0- 3) به روش ساده سرتاسری و تکی ساده بخیه شد. در آزمون فرمالین، سیمواستاتین، (mg/kg2، 4 و 8) یا مورفین (mg/kg5) به موش ها تزریق شد. در موش ها تزریق همزمان سیمواستاتین (mg/kg8) + نالوکسان (mg/kg2) یا سپروهپتادین (mg/kg 4)، سایمیتیدین (mg/kg12.5)، انجام شد. سپس تست فرمالین صورت گرفت و زمان لیسیدن اندازه گیری شد. حیوانات به 4 گروه تقسیم شدند: گروه 1: آسیب عصبی بدون درمان، گروه 2و3 و4 گروه های درمان با سیمواستاتین بود. موش های گروه 2 (با دوز  mgkg 2) و گروه 3 (با دوزmgkg 4) و گروه 4 (با دوزmgkg 8) تحت درمان با سیواستاتین قرار گرفتند. در هر گروه 5 سر موش قرار گرفت که در دو بازه ی زمانی 2 و 4 هفته مورد ارزیابی قرار گرفتند. تحلیل آماری داده های حاصله با استفاده از نرم افزار IBM SPSS Statistics 26  (SPSS25)، انجام شد.

    یافته ها

    یافته های توصیفی متغیرهای موردمطالعه، شامل شاخص هایی از قبیل میانگین، انحراف معیار، خطای استاندارد و... محاسبه و گزارش گردید.

    نتیجه گیری

    براساس نتایج به دست آمده به نظر می رسد که سیمواستاتین با دز mg/kg 8 در کاهش زمان عکس العمل درد در گروه تحت درمان تاثیر دارد.

    کلید واژگان: سیمواستاتین, کاهش زمان تحمل درد, موش صحرایی}
    Mahtab Mohammadzadeh, Ahmad Asghari*, Shahin Hasanpour
    Background & Aims

    Pain is divided into two main types, fast and slow. Pain receptors are composed of free nerve endings and use two separate pathways to transmit pain signals to the CNS. Sharp pain signals are produced by mechanical and thermal pain stimuli. These signals are transmitted to the spinal cord by peripheral nerves through Aδ fibers at a speed of 3-15 m/s. On the contrary, slow and chronic pain signals are mainly produced by chemical pain stimuli, but sometimes stable mechanical or thermal stimuli can also produce these signals. These signals are transmitted to the spinal cord by C-type fibers at a speed of 0.5 to 2 m/s (1).The mechanisms of neuropathic pain are not fully known, but the mechanisms proposed in the pathogenesis of this pain include the role of glial cells as supporting cells of the central nervous system, changes in sodium and potassium voltage-dependent channels, afferents adjacent to the neuron. It is damaged. Different neural pathways are affected differently. Therefore, identification of these pathways is important in determining the analgesic and medicinal mechanisms from physiological aspects. Although there are many studies in this field, one of the existing problems is the rate of recovery and return of nerve activity after injury. The results of researchers' research have brought relatively acceptable results, which were not without problems. In the present research, due to the high incidence of peripheral nerve injuries caused by blows and fractures in humans and animals, efforts will be made to find a drug or drug combination to accelerate the healing process of damaged nerves following experimental sciatic nerve injury in the rat animal model. Therefore, the present study will be conducted in order to investigate the analgesic effects of simvastatin and its neurophysiological interaction with the involved systems following experimental sciatic nerve ligation in rats.

    Methods

    This research was used in 2 experimental phases on 85 adult male rats weighing 180-200 grams. These animals were transferred to the laboratory animal breeding and maintenance center of the veterinary school and were kept in standard mouse cages under standard conditions. All animals were evaluated for motor health before surgery, and then all mice were anesthetized by intraperitoneal injection of ketamine hydrochloride (60 mg/kg) and xylazine (10 mg/kg), and after scrubbing and initial leg preparation The animals were placed on their left side and an incision was made in the posterior-external skin of the thigh area of ​​the left leg. The muscles and fascia were gently removed and after exposing the sciatic nerve, the sciatic nerve was compressed for 60 seconds using a micro hemostat. In order to trace, the injury site is marked by suturing the muscle closest to the crush site using non-absorbable silk suture (0-5) and then the muscles are placed together and the subcutaneous tissue and skin are The sequence was stitched using vicryl thread (0-4) and nylon (0-3) in a simple all round and single stitch method. Then formalin test was done and licking time was measured. The animals were divided into 4 groups: group 1: nerve damage without treatment, group 2, 3 and 4 were treated with simvastatin. Mice in group 2 (with a dose of 2 mg/kg), group 3 (with a dose of 4 mg/kg) and group 4 (with a dose of 8 mg/kg) were treated with Sivastatin. There were 5 mice in each group and they were evaluated in two time intervals of 2 and 4 weeks.

    Results

    As seen in Figure 1, the injection of morphine (5 mg/kg) significantly reduced the pain time caused by the formalin test compared to the control group (P<0.05). The level of 4 and 8 mg/kg simvastatin significantly decreased the pain time caused by the formalin test compared to the control group (P<0.05).According to the results of the statistical analysis of repeated measurements of one factor, the summary of the analysis of variance of the changes in the duration of the animal's response to the stimulating effects of formalin affected by the effective dose (8 mg/kg) of simvastatin compared to naloxone during the acute and chronic phases is presented in Figure 2.Naloxone injection (2 mg/kg) had no effect on pain time caused by formalin test compared to the control group (P>0.05). The level of 8 mg/kg simvastatin significantly decreased the pain time caused by the formalin test compared to the control group (P<0.05). The combined injection of naloxone plus simvastatin significantly reduced the analgesic effects of simvastatin compared to the simvastatin alone group (P<0.05).According to the results of the statistical analysis of the repeated measurements of one factor, the summary of the analysis of variance of the changes in the duration of the animal's response to the stimulating effects of formalin affected by the effective dose (8 mg/kg) of simvastatin compared to speroheptadine during the acute and chronic phases is presented in Figure 3.According to the results of the statistical analysis of the repeated measurements of one factor, the summary of the analysis of variance of the changes in the duration of the animal's response to the stimulating effects of formalin affected by the effective dose (8 mg/kg) of simvastatin compared to cimetidine during the acute and chronic phases is presented in graph No. 4 .

    Conclusion

    The aim of this study is the analgesic effects of simvastatin following experimental sciatic nerve ligation in rats. According to the obtained results, it was determined that the analgesic effects of simvastatin are dose-dependent and the findings of this test show that the effective dose (8 mg/kg) of simvastatin alone has been able to create a significant effect in reducing the painful effects of formalin in animals. It has also caused a significant decrease in the response time to formalin pain stimulus in animals. Antagonists naloxone, cyproheptadine and cimetidine were able to inhibit the analgesic effects in acute and chronic phase. Simvastatin activates the PI3K/AKt pathway and increases neurogenesis through BDNF and (Vascular endothelial growth factor) (12). Simvastatin increases the phosphorylation and expression of BDNF and VEGF gene in (Dentate gyrus) DG. As a result, cell proliferation increases and differentiation occurs in the DG area and brain recovery increases (14). Therefore, simvastatin may cause gene expression of growth factors, production of protein kinases, and subsequent induction of neurogenesis in the DG of the hippocampus, increasing dendritic branches through the activation of AKt through the signaling pathway (15). The effects of simvastatin on ischemia-reperfusion injury of the sciatic nerve in adult rats, as a result, administration of simvastatin before ischemia shows protective properties in nerve re-injury and improves blood supply again (16).

    Keywords: Simvastatin, Reduction of Pain Tolerance Time, Rats}
  • Xuemeng Chen, Li Xie, Wei Wu *
    Objective (s)

    Increased oxidative stress and inflammatory response are risk factors for kidney and cardiovascular diseases in patients with hyperuricemia. Uric acid (UA) has been reported to cause inflammation and oxidative damage in cells by inhibiting the nuclear factor E2-related factor 2 (Nrf2) pathway. Notably, Simvastatin (SIM) can regulate the Nrf2 pathway, but whether SIM can regulate inflammatory response and oxidative stress in vascular endothelial cells induced by high UA via this pathway has not been clarified.

    Materials and Methods

    To demonstrate this speculation, cell activity, as well as apoptosis, was estimated employing CCK-8 and TUNEL, respectively. Indicators of oxidative stress and inflammation were assessed by related kits and western blotting. Subsequently, the effects of SIM on signaling pathways were examined using western blotting.

    Results

    The result showed that after UA exposure, oxidative stress was activated and inflammation was increased, and SIM could reverse this trend. Meanwhile, SIM could inhibit high UA-induced apoptosis. In addition, western blotting results showed that SIM reversed the down-regulation of the expression of Nrf2 pathway-related proteins caused by high UA.

    Conclusion

    SIM alleviated the inflammatory response as well as inhibiting oxidative stress through the Nrf2 pathway, thereby attenuating high UA-induced vascular endothelial cell injury.

    Keywords: Inflammation, Nrf2 signaling, Oxidative stress, Simvastatin, Uric acid, Vascular endothelial cells}
  • Tourandokht Baluchnejadmojarad *, Javad Fahanik-Babaei, Soraya Mehrabi, Mehrdad Roghani
    Background and Objective

    Alzheimer’s disease (AD) as the most common neurodegenerative disorder. Klotho is an anti-aging protein with important roles in neurodegenerative disorders. This study was done to evaluate the expression of klotho gene and protein in the plasma of AD patients treated with blood pressure control drugs (inhibitors of angiotensin-converting enzyme (ACE)) or blood lipids control drug (simvastatin).

    Materials and Methods

    Target population was selected from people with AD who visited the neurology clinic of Firouzgar hospital. The tested groups included the control group, Alzheimer's group, Alzheimer's group treated with blood pressure control drugs, and Alzheimer's patients group treated with blood lipid control drug. Expression of klotho gene and protein in the plasma of studied groups was determined using real-time PCR and ELISA techniques and the individual's cognitive disorders were also evaluated using Mini-Mental State Exam (MMSE) and Clinical Dementia Rating (CDR) tests.

    Results

    The results obtained in this study showed that in addition to the significant difference in cognitive indices between the control groups and three groups of Alzheimer's patients, the level of klotho gene and protein expression was also lower in three groups of Alzheimer's patients compared to healthy group. However, there was no significant difference (p>0.05) between the Alzheimer's group and the two Alzheimer's groups treated with blood pressure or blood lipid control drugs.

    Conclusion

    Drugs controlling blood pressure or blood lipids in Alzheimer's patients possibly have no significant effect on the level of klotho protein. Obviously, more studies are needed in this field.

    Keywords: Alzheimer’s disease, Klotho, Angiotensin-converting enzyme, Blood lipids, Simvastatin}
  • Saeed Rahimi, Negin Ghasemi, Paria Davoudi, Isun Taleb, Mehran Farajollahi *, Naghmeh Rahimi Darehchi, Ezatolah Kazeminejad
    Background

    This study assessed the antimicrobial effects of different concentrations of simvastatin versus triple antibiotic paste (TAP) on Enterococcus faecalis biofilms at different stages of development.

    Methods

     In this in vitro study, 70 human single-rooted mature premolars were decoronated, instrumented, and autoclave-sterilized. Next, an E. faecalis suspension was prepared and inoculated into the canals to obtain 4- and 6-week biofilms. After ensuring biofilm formation, the samples in each group were randomly assigned to 5 subgroups (n=12): 1 mg/mL TAP, 10 mg/ mL TAP, 1 mg/mL simvastatin, 10 mg/mL simvastatin, and positive control (phosphate-buffered saline solution). The medicaments were applied in the canals, and the teeth were incubated for one week. Dentin samples were collected by a rotary file, cultured, and the number of E. faecalis colonies was counted. The Kruskal-Wallis, Mann-Whitney U, and Wilcoxon tests were used for data analysis (α=0.05).

    Results

    There were significant differences in colony counts between the two concentrations of TAP and the control group against both 4- and 6-week biofilms (P<0.05). The antibacterial effect of 10 mg/mL TAP and simvastatin was stronger than that of 1 mg/mL concentration against the 4- and 6-week E. faecalis biofilms (P<0.05). Furthermore, 10 mg/mL TAP and simvastatin were more effective against the 4-week biofilms than the 6-week biofilms (P<0.05).

    Conclusion

    According to the present results and since biofilms may remain viable in the root canal system for weeks to months, applying 10 mg/mL TAP and simvastatin might be more effective.

    Keywords: Enterococcus faecalis, Antibacterial agents, Simvastatin, Root canal preparation}
  • Iman Parisay, Ali Qeidari, Ehsan Sabouri, Fatemeh Khorakian, Hosein Bagheri
    Background

    This study aims to compare cytotoxicity and induced apoptosis of a new bioceramic cement containing different concentrations of simvastatin on stem cells from human exfoliated deciduous teeth (SHED).

    Materials and Methods

    This research was an in vitro study. To evaluate the cytotoxicity and induced apoptosis of the bioceramic cement containing different concentrations of simvastatin, the SHED were exposed to the cement during 1, 3, and 7 days. Pure bioceramic cement and pure simvastatin with concentrations of 1, 0.1, and 0.01 µM were also tested to evaluate the possible synergic effect. Mineral trioxide aggregate (MTA) as the gold standard of pulp dressing materials was compared. MTT assay and Annexin V assay were used to evaluate cytotoxicity and induced apoptosis, respectively. The data were analyzed using ANOVA and Tukey post hoc tests at the significance level of 0.05.

    Results

    During 7 days, MTA, bioceramic cement, simvastatin 0.1 and 0.01 µM, and bioceramic cement containing 0.1 and 0.01 µM simvastatin increased (P < 0.05) and simvastatin with concentration of 1 µM decreased the cell viability (P < 0.05). Except for MTA and bioceramic cement containing 0.1 and 0.01 µM simvastatin, all other compounds induced apoptosis within 7 days (P < 0.05).

    Conclusion

    After 7 days, the viability of the SHED in the presence of a new bioceramic cement containing 0.1 and 0.01 µM simvastatin was not compromised. Moreover, this cement showed superior results than MTA and provided an environment for cell proliferation. This finding appears to be due to the pharmacological effects of low concentrations of simvastatin.

    Keywords: Apoptosis, mineral trioxide aggregate cement, simvastatin, toxicity}
  • مینا جعفری، ویدا حجتی*، مهدی خاکساری، غلامحسین واعظی
    هدف

    قرارگیری در معرض اتانول به عنوان یک نوروتراتوژن در دوره تکوین اثرات مخربی بر سیستم عصبی مرکزی دارد و باعث اختلالات عصبی در بزرگسالی است این اختلالات با آپوپتوز در مناطقی از مغز مانند هیپوکامپ, با فعال شدن آبشار اکسیداتیو- التهابی و سطح بالای دژنراسیون عصبی مرتبط است. سیمواستاتین که به عنوان دارو برای درمان هیپرکلسترومی استفاده می شود, می تواند از سد خونی مغزی عبور کرده و آثار نوروپروتکتیو آن در چندین بیماری سیستم عصبی مورد تایید قرار گرفته است. هدف این پژوهش، ارزیابی فعالیت های محافظتی سیمواستاتین بر روی اختلالات حافظه و نکروز سلول های عصبی در هیپوکامپ موش صحرایی با قرار گرفتن در معرض الکل پس از تولد بود.

    مواد و روش ها

     نوزادان نر موش 27/5 گرم در کیلوگرم اتانول محلول در شیر خشک را از طریق گاواژ در روزهای 10-2 بعد از تولد دریافت کردند. هم چنین 10 و 20 میلی گرم بر کیلوگرم سیمواستاتین را به شکل زیر جلدی در روزهای 10-2 بعد از تولد دریافت کردند. اختلالات حافظه شناختی 36 روز پس از تولد از روش تشخیص شیء جدید ارزیابی شد و سپس میزان سلول های نکروز شده از طریق رنگ آمیزی نیسل بررسی شد.

    یافته ها

     داده های رفتاری نشان داد که در گروه های تیمار شده با سیمواستاتین حافظه تشخیص شیء جدید نسبت به گروه اتانول افزایش یافته (01/0>P). بعلاوه در گروه اتانول افزایش مرگ سلولی در ناحیه CA1 هیپوکامپ مشاهده گردید که تیمار با سیمواستاتین کاهش معنی داری در میزان سلول های نکروتیک  نشان داد (01/0>P).

    نتیجه گیری

     این مطالعه نشان داد که سیمواستاتین اثر محافظتی بر نقایص عصبی مرتبط با الکل دارد،هرچند که تحقیقات بیش تر در آینده مورد نیاز است.

    کلید واژگان: سیمواستاتین, اتانول, حافظه, مرگ سلولی, هیپوکامپ}
    Mina Jafari, Vida Hojati*, Mehdi Khaksari, Gholamhassan Vaezi
    Introduction

    Exposure to ethanol as a neurotratogen in the developmental period has destructive effects on the central nervous system and causes neurological disorders in adulthood. These disorders are associated with apoptosis in areas of the brain such as the hippocampus, by activating the oxidative-inflammatory cascade and high levels of nerve degeneration. Simvastatin, used as a drug to treat hypercholesterolemia, can cross the blood-brain barrier and its neuroprotective effects have been confirmed in several diseases of the nervous system. This study aimed to evaluate the protective activities of simvastatin on memory disorders and nerve cell necrosis in the rat hippocampus by postnatal alcohol exposure.

    Materials and Methods

    Male rat infants received 5.27 g / kg milk powder soluble ethanol on days 2-10 after birth by gavage. They also received 10 and 20 mg/kg of simvastatin on days 2-10 after birth subcutaneously. Cognitive memory abnormalities were assessed 36 days after birth by the new object detection and then, the number of necrotic cells was assessed by nissl staining.

    Results

    Behavioral data showed that in the groups treated with simvastatin, the new object recognition memory increased compared to the ethanol group (P<0.01). In addition, in the ethanol group, an increase in cell death was observed in the CA1 region of the hippocampus, and treatment with simvastatin showed a significant decrease in the number of necrotic cells (P<0.01).

    Conclusion

    This study showed that simvastatin has a protective effect on alcohol-related neurological defects, although more research is needed in the future.

    Keywords: Simvastatin, Ethanol, Memory, Cell Death, Hippocampus}
  • Armin Ahmadi, Shayan Ebadi, Tahereh Tayebi, Alireza Ebadi, Hassan Niknejad*

    Bone tissue engineering has shown a promising way in order to renew bone defects without conflicting with previously known side effects. Three main building blocks including seeding cells, scaffold, and signaling molecules are required for this process. The human amniotic membrane (hAM) is the innermost of the placental membranes. As well as providing a source of stem cells and growth factors, hAM has several features which make it an appropriate stem cell containing scaffold in order to be used in orthopedic surgery. The present investigation aimed to demonstrate the effect of bone morphogenetic protein-9 (BMP-9) alongside phenamil and simvastatin on osteogenic induction of hAM with its sessile epithelial cells (hAECs). For this purpose, hAM was cultured using six different osteogenic media for 14 days. The basic osteogenic media was chosen as the first group and other media were made by addition of BMP-9, phenamil, simvastatin, BMP-9 alongside phenamil, and BMP-9 alongside simvastatin to the basic osteogenic media. Finally, viability, mineralization, calcium and phosphate content, lactate dehydrogenase (LDH), and alkaline phosphatase (ALP) activity were evaluated. Among all study groups, simvastatin-containing groups showed a significantly lower level of viability. Although, all media could induce osteogenic features, the hAECs which were cultured in media containing BMP-9 and phenamil could demonstrate a wider area of mineralization and a significantly higher level of calcium, phosphate, LDH, and ALP activity. These findings indicated that the application of phenamil alongside BMP-9 could synergistically show in situ osteogenic induction in hAECs.

    Keywords: Bone morphogenetic protein-9, Phenamil, Simvastatin, Amniotic epithelial stem cells, Osteogenic differentiation, Tissue engineering}
  • Iman Parisay, Ali Qeidari, Ehsan Sabouri, Fatemeh Khorakian, Hosein Bagheri
    Background

    This study aims to compare cytotoxicity and induced apoptosis of a new bioceramic cement containing different concentrations of simvastatin on stem cells from human exfoliated deciduous teeth (SHED).

    Materials and Methods

    This research was an in vitro study. To evaluate the cytotoxicity and induced apoptosis of the bioceramic cement containing different concentrations of simvastatin, the SHED were exposed to the cement during 1, 3, and 7 days. Pure bioceramic cement and pure simvastatin with concentrations of 1, 0.1, and 0.01 µM were also tested to evaluate the possible synergic effect. Mineral trioxide aggregate (MTA) as the gold standard of pulp dressing materials was compared. MTT assay and Annexin V assay were used to evaluate cytotoxicity and induced apoptosis, respectively. The data were analyzed using ANOVA and Tukey post hoc tests at the significance level of 0.05.

    Results

    During 7 days, MTA, bioceramic cement, simvastatin 0.1 and 0.01 µM, and bioceramic cement containing 0.1 and 0.01 µM simvastatin increased (P < 0.05) and simvastatin with concentration of 1 µM decreased the cell viability (P < 0.05). Except for MTA and bioceramic cement containing 0.1 and 0.01 µM simvastatin, all other compounds induced apoptosis within 7 days (P < 0.05).

    Conclusion

    After 7 days, the viability of the SHED in the presence of a new bioceramic cement containing 0.1 and 0.01 µM simvastatin was not compromised. Moreover, this cement showed superior results than MTA and provided an environment for cell proliferation. This finding appears to be due to the pharmacological effects of low concentrations of simvastatin.

    Keywords: Apoptosis, mineral trioxide aggregate cement, simvastatin, toxicity}
  • Dyah Oktarina *, Roihan Iqbal
    Background
    Simvastatin is a beta-hydroxy-beta-methylglutaryl- CoA (HMG-CoA) inhibitor molecule with several pleiotropic (immunomodulatory, anti-inflammatory, and antioxidant) activities. In this study, we evaluated the protective effect of simvastatin on ultraviolet B (UVB)-induced photoaging of normal human dermal fibroblast cultures by assessing fibroblast proliferation, collagen deposition, and fibroblast morphology.
    Methods
    This study was an in vitro experiment using normal human skin fibroblast cell cultures. Fibroblasts were then cultured and observations were made of fibroblast proliferation, collagen deposition, and cell morphology using various concentrations of simvastatin (0 nM, 0.01 nM, 0.1 nM, 0.5 nM, 1 nM, and 5 nM) and UVB exposure (100 mJ/cm2).
    Results
    After UVB exposure, a significant decrease in fibroblast proliferation and collagen deposition was observed. Cells appeared thinner, and fibroblasts were less organized and more pointed. Simvastatin with 0.01 nM, 0.1 nM, 0.5 nM, 1 nM, and 5 nM levels could significantly maintain cell proliferation and collagen deposition compared to UVB-irradiated cell groups without simvastatin. Interestingly, fibroblast proliferation and collagen deposition in the simvastatin group above 0.5 nM were not significantly different from the normal human dermal fibroblast group. An increased level of collagen deposition was also confirmed by observing the fibroblast morphology, which had more red-smeared cells on Sirius red staining. The antioxidant activity of simvastatin might play a role in fibroblast proliferation and collagen deposition, protecting against UVB by inhibiting reactive oxygen species. Simvastatinmaintained fibroblast morphology, possibly by preventing DNA damage and maintaining membrane-bound collagen fiber deposition.
    Conclusions
    Our findings revealed that simvastatin pretreatment mitigated UVB-induced photoaging in human dermal fibroblast cells by maintaining fibroblast proliferation, collagen deposition, and fibroblast morphology.
    Keywords: Fibroblast, photoaging, Simvastatin, UVB}
  • Matina Pourghasem, Gita Sadighi*, Arash Mirabzadeh
    Objectives

    As a severe mental health condition, schizophrenia presents a chronic and complex clinical manifestation and neuropathology. A large body of literature exists on the pharmacological treatment of schizophrenia. However, evidence on some dimensions of such interventions (e.g., eligible candidates, potential predicting factors of the therapeutic outcomes, safe implementation of these interventions, etc.) are notably scarce. Studies revealed superior influences of adjunct statin therapy over placebo among patients with schizophrenia. The study aimed to investigate the effects of aspirin and simvastatin as adjunctive therapy, compared to placebo on positive and negative symptoms and general psychopathology of patients with schizophrenia.

    Methods

    This is a double-blind, randomized clinical trial. The sample size was estimated to be 15 individuals for each one of the three research groups (n=45). The Positive And Negative Syndrome Scale (PANSS) and the Hamilton Rating Scale For Depression (HAM-D) were employed to collect the study data in the present study. The study patients were recruited from patients admitted to the psychiatric wards of Razi Hospital were identified. The study subjects were randomly divided into two test groups and one control group. All groups were initially treated with risperidone 4 mg daily for 3 weeks. Then, group A received aspirin (325 mg twice daily), whereas group B was prescribed 40 mg/d of simvastatin. However, the control group received a placebo. Psychiatric symptoms were recorded according to the PANSS at the beginning of the study and then at weeks 4 and 8. The results were analyzed using inferential statistics (repeated-measures analysis of covariance) and descriptive statistics in SPSS software v. 20.

    Results

    Of 45 patients, 35(77.78%) were men (Mean±SD age: 45.8±10.5 years), and 10(22.23%) were women (Mean±SD age: 42.3±7.8 years). The mean scores of the positive symptoms of PANSS significantly decreased in the groups treated with aspirin and simvastatin (P=0.006 and P=0.005, respectively). However, no such difference was seen in the controls (P=0.447). Furthermore, the mean scores of the negative symptoms of PANSS significantly decreased in the intervention groups (P<0.001); in addition, no significant differences were seen in the controls after the end of the research program (P=0.18). In addition, the mean scores of the general symptoms of PANSS significantly decreased in the aspirin and simvastatin groups (P<0.001). There was an increase in the same value in the controls, but the increase was not significant (P=0.31). Finally, while the total mean scores of the PANSS increased in the control group (P=0.25), the corresponding scores significantly decreased in the test groups receiving aspirin and simvastatin (P<0.001).

    Discussion

    The present study results indicate that either aspirin or simvastatin can reduce the symptoms of schizophrenia, including general psychopathology, negative symptoms, and positive symptoms in the explored patients. Also, the effectiveness of both drugs was similar, and no significant difference was detected between these medications in reducing the symptoms mentioned above.

    Keywords: Aspirin, Simvastatin, Negative symptoms, Positive symptoms, General psychopathology, Schizophrenia}
  • MohammadSaleh Ranaiy, Farah Farokhi*, Farrin Babaei Balderlou
    Background & Objective

     

    The simvastatin (Sim) is a lipophilic statin and can cross the blood-brain barrier. The role of vitamin D (Vit D) in brain development and function has been supported over the past decade. This study aimed to evaluate the effect of simvastatin on memory and anxiety levels in healthy male rats.

    Materials & Methods

    In this experimental study, 36 male Wistar rats weighing 250-300 g were randomly divided into six groups (n=6) including control, Vit D (5 µg/kg/day; IP), Simvastatin (1 mg/kg/day; orally) (SimL), Simvastatin (10 mg/kg/day; orally) (SimH), SimL + Vit D and SimH + Vit D. After 28 days, at the end of the treatment, the behavioral anxiety test and memory behavioral test were performed. Then, the rats were euthanized, and oxidative stress markers of the brain, serum low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and cholesterol levels were investigated. Data were analyzed by SPSS 24 software and Tukey’s test.

    Results

     Co-administration of simvastatin and vitamin D significantly increased working memory, catalase activity, total antioxidant capacity, HDL-C, and decreased anxiety levels, malondialdehyde (MDA) concentration, cholesterol, and LDL-C compared to the control group (p<0.05). However, the administration of simvastatin and vitamin D alone did not significantly change the mentioned parameters compared to the control group (p>0.05).

    Conclusion

    Co-administration of simvastatin and vitamin D can improve brain function by reducing oxidative stress and cholesterol levels.

    Keywords: Anxiety, Simvastatin, Vitamin D, Working memory, Rat}
  • Kiyarad Edris, Gholamreza Najafi Tazekand*, Farah Farrocki
    Background & Objective

    Cardiovascular diseases (CVDs) are the deadliest disease globally, which in order to reduce this mortality rate statin has been used during last decades. In line, it has been revealed that statins negatively affect testicular tissue. Thus, in the current project, we aimed to investigate the vitamin D protective effects during simvastatin (SIM) administration.

    Materials & Methods

    In this project, 48 male mature Wistar rats were randomly divided into 6 control and experimental groups. The experimental groups were subdivided into Low and High dose SIM-received and Vitamin D co-treated SIM-received groups. After 45 days, the body weight of the animal groups was measured and then they were euthanized and testicles were removed. The right testicular tissue was fixed in fixative solution, while the left testicular tissue was used for biochemical and molecular analysis. To evaluate the pathological changes, hematoxylin and Eosin (H&E) staining were performed. The Malondialdehyde (MDA), Total antioxidant capacity (TAC), catalase (CAT) and Ferric-reducing antioxidant power (FRAP) levels were examined in order to evaluate the Reactive oxygen species (ROS) and antioxidant levels. Finally, Bax, Bcl-2, p53 and Caspase-3 mRNA levels were analyzed using real- time PCR.

    Result

    Our observations revealed that the MDA, Bax, p53 and caspase-3 level enhanced in the sole-SIM-received groups compared to control group, while level of TAC, catalase and Bcl-2 diminished in SIM-received groups versus control group. In contrast, Vitamin D-co-treated animals showed a significant enhancement in level of TAC, catalase and Bcl-2 compared to sole-SIM-received animals (p≤0.05).

    Conclusion

    The vitamin D-co-administration can positively protect testicular tissue against SIM-induced oxidative stress condition by enhancing enzymatic activity of antioxidant defense and anti-apoptotic genes activation.

    Keywords: Antioxidant, Apoptosis, Simvastatin, Stress oxidative, Vitamin D}
  • Saeed Rahimi, Negin Ghasemi, Golchin Jabbari, Zahra Zaheri, Zahra Sadat Torabi, Naghmeh Rahimi Darehchi
    Background

    The effect of different intracanal medicaments on root fracture resistance has not been thoroughly investigated in the short and long term. To assess the effect of calcium hydroxide (CH), CH combined with Chlorhexidine (CHX), double antibiotic paste (DAP), and simvastatin as intracanal medicaments on the fracture resistance of the human root. One hundred and twenty single‑rooted mandibular premolars which were extracted for periodontal reasons were collected for this in vitro study.

    Materials and Methods

    This was an in vitro study. All teeth were decoronated. Root canals were prepared by the Pro taper system, and %2.5 NaOCl was used for irrigation. The smear layer was removed using %5.25 NaOCl and 17% ethylenediaminetetraacetic acid each for 3 min. The samples were randomly divided into five groups based on the medicament: (1) CH (2) CH + CHX (3) Simvastatin (4) DAP (5) Control group. All specimens in each group were incubated for 1 week (Subgroup A) and 1 month (Subgroup B).Then, medicaments were removed and filled with gutta‑percha and AH26 sealer. All samples were tested for fracture resistance.The data were statistically evaluated with the SPSS software 17.ANOVA and Mann– Whitney U and Wilcoxon tests were used for the analysis of the data. P = 0.05 was considered statistically significant.

    Results

    Although CH and CH + CHX increased the fracture resistance in a 1‑week period, there was no significant difference between the groups after 1 month.

    Conclusion

    Under the limitations of this study, CH and CH + CHX, DAP and simvastatin do not have a negative effect on root fracture resistance when used as intracanal medicaments for <1 month.

    Keywords: Calcium hydroxide, chlorhexidine, root canal, simvastatin, therapy}
نکته
  • نتایج بر اساس تاریخ انتشار مرتب شده‌اند.
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