Savas Aktas

Purpose: Atractylenolide III (ATR III) is known for its anti-inflammatory and neuroprotective activities. In this study, we aimed to investigate the effects of ATR III on neuronal damage in temporal epileptic rats caused by kainic acid. Materials and Methods: 16-week-old Wistar Albino rats were divided into three groups; control (C, n=8), kainic acid (KA, n=8), ATR III+ kainic acid (KA+ATR, n=8). After 21 days of injections of kainic acid, learning, and memory behavior, anxiety, and locomotor activity were evaluated. Neuron morphologies in the hippocampus were examined, the total number of neurons, and the number of degenerated neurons were determined, and the thickness of these regions was also measured. Changes in biochemical parameters such as MDA, SOD, GSHPx, AChE, and CAT were investigated to detect oxidative stress in the brain. Results: There was no significant difference in the learning and memory function and locomotor activity. However, KA increased anxiety behavior without any effect of ATR III (closed arm duration, 244.90±25.17). There was no degeneration in the neurons of the control group. In the KA group, there was an increase in the number of degenerated neurons. In this group, the thicknesses in CA1, CA3, and DG regions were 37.39±1.90, 45.64±6.26 and 46.02±5.72 µm, respectively. In the ATR III+KA group, there were fewer degenerated neurons, less thinning of the hippocampus, and a higher number of normal neurons compared to the KA group. In this group, CA1, CA3, and DG thicknesses were calculated as 36.05±4.13, 47.09±7.09 and 43.07±5.91 µm, respectively. Conclusion: These findings suggest that ATR III may have the potential as a therapeutic agent for reducing neuronal damage in temporal epilepsy. Further research is warranted to explore the underlying mechanisms and evaluate the clinical implications of ATR III in the treatment of epilepsy.

Objective: Burn may cause hypersensitivity towards infection, systemic inflammatory response syndrome, respiratory distress syndrome and multiple organ failure. Anti-inflammatory and resistance towards infection effects of omega-3 (n-3) fatty acids was shown before. But their effect on systemic inflammation and wound healing after burn was not investigated. Methods: Seventy Wistar albino rats were used in the study. Fourteen rats without burn composed the control group. Cutaneous burn was created on remaining 56 rats which received 50 mg/kg/day intraperitoneal ringer lactat solution in two equal amounts. Twenty-eight rats with burn received injections of n-3 1 mg/kg/day throughout the study. Rats in control group were sacrificed on day 4 and rats in treatment groups were sacrificed on days 4 and 8. Leukocyte and mast cell infiltration, epidermal and collagen thickness measurements were used in histological evaluation. White blood cell, hematocrite, total protein, albumin, fibronectin, TNFα, IL1β and IL6 levels were measured for biochemical evaluations. Results: Elevation of leukocyte and mast cell infiltration was lower and collagen thickness was higher in n-3 receiving group on day 4. There was no difference in leukocyte infiltration on the 8th day whereas mast cell infiltration was lower and collagen thickness was higher in n-3 receiving group. Epidermal thickness was higher in n-3 receiving group on both evaluation days. White blood cell counts were higher in 8th day than 4th day groups. Total protein on 8th, IL-6 on 4th, and albumin levels on both days was lower than control. Conclusion: N-3 fatty acids used after burn enhances wound healing and prevents systemic inflammation.

Endometrial cancer is the most common cancer of the female reproductive system. Combination treatment with specific agents has been widely used as a targeted therapy for cancer. In this study, we aimed to investigate the anti-proliferative and apoptotic effects of varying concentrations of perifosine and vitamin D on the human endometrial cancer cell line (HEC-1A). HEC-1A cells were exposed to perifosine (10 μM, 30 μM), vitamin D (50 nM, 200 nM) and combinations of both for 48 h and 72 h. Monitoring of cell proliferation in a time-dependent manner was performed with the xCELLigence RTCA DP system. The levels of BCL2, BAX and P53 mRNA expression were examined using RT-qPCR. Apoptosis was determined using Annexin V, which were followed by flow cytometry analysis. Ultra-structural morphology of cells was analyzed by transmission electron microscopy (TEM) for 72 h. The anti-proliferative and apoptotic effects of the perifosine+vitamin D combination (30 μM + 200 nM at 48 h and 10 μM + 200 nM at 72 h) on HEC-1A cells were higher than in perifosine and vitamin D alone. It was observed that perifosine has increased the expression of BAX mRNA in HEC-1A cells in a dose-dependent manner. While perifosine+vitamin D combinations increased P53 mRNA expression in HEC-1A cells we did not find any significant change in BCL2, BAX mRNA expression levels. In TEM examinations of HEC-1A cells, perifosine appeared to lead autophagic cell death, whereas vitamin D caused paraptosis-like cell death and combination of perifosine+vitamin D caused apoptotic and non-apoptotic (paraptotic, autophagic and necrotic) cell death. Therefore, it is considered that the combination of both drugs in the treatment of endometrial cancer might be an alternative and effective treatment option through activating the apoptotic and non-apoptotic cell death mechanisms in cancer cells.

This study aimed to evaluate the protective role of paricalcitol, a vitamin D analog, against hazardous effects of 1800-MHz radiofrequency (RF) radiation on the skin of male Wistar albino rats exposed one h/day for 4 weeks. The maximum specific absorption rate was calculated as 0.0042 W/kg. Superoxide dismutase and catalase activity, collagen bundle thickness, breaking force, energy, and stress were decreased, while malondialdehyde level and mast cell number were increased. The exposure to 1800-MHz RF radiation caused a reduction in skin biomechanical quality through oxidative stress and mast cell activation. The administration of paricalcitol caused a significant improvement.

OBJECTIVE: This study planned to evaluate the effects of vitamin A (VA) and steroid treatment on nerve healing. Study design: we investigated electrophysiological, electron microscopic (EM), immunohistochemical, and biochemical findings in rat sciatic nerve model. MATERIALS and METHODS: In total, 112 female rats were divided into 16 groups, each consisting of 7 animals. Subjects were evaluated according to compound muscle action potential (CMAP) findings, ultrastructural staging of myelinated axons with EM, nitric oxide (NO) and malondialdehyde (MDA) findings in serum and tissue, and immunohistochemical findings in the first week and first month. RESULTS: NO and MDA levels in serum and tissue were found to be statistically lower after high-dose methylprednisolone (MP), normal-dose MP, high-dose MP+VA, normal-dose, and MP+VA treatment modalities compared to controls (p<0.05). The most similar EM findings compared to control animals were seen in the normal-dose MP and high-dose MP+VA treatment groups. The best amplitude values were seen in the high-dose MP and continuous normal-dose MP therapy groups in the first month. In the normal-dose MP and high-dose MP+VA treatment groups, intense staining was found compared to the control and sham groups according to the sciatic nerve immunohistochemical examination. CONCLUSION: This study revealed noticeable VA effects on the inflammatory process during the healing of traumatic nerve paralysis by electron microscopy and immunohistochemistry. However, similar findings were not established by electrophysiology. Therefore, more experimental studies are needed to further investigate the efficacy and the mechanism of action of VA on steroid administration and the inflammatory process.

Amaç: Kronik arteryel iskemi tedavisinde cerrahi ve invazif girişimler yapılmaktayken bu yöntemlerin yetersiz kaldığı durumlarda tedavi seçeneklerinden biri terapötik anjiyogenezistir. Çalışmamızda, terapötik anjiyogeneziste yeni ve kontrollü bir süreç oluşturmak amacıyla, arka bacaklarında kronik arteryel iskemi oluşturulan ratlara, intramusküler lipoteikoik asit enjeksiyonu yapıldı ve anjiyogenezis süreci değerlendirildi. Yöntem: Gruplardaki rat sayısı istatistiksel yöntemle belirlenerekherbirinde onar rat bulunan toplam dört grup oluşturuldu. Kontrol grubuna herhangi bir işlem uygulanmadı, iskemi grubuna kronik iskemi modeli oluşturuldu, serum fizyolojik grubuna iskemi oluşturulduktan sonra serum fizyolojik enjeksiyonu yapıldı, lipoteikoik asit grubuna iskemi oluşturulmasını takiben intramusküler lipoteikoik asit enjeksiyonu yapıldı. Ratlar laboratuvar ortamında otuz gün boyunca vital bulgular ve enfeksiyon açısından takip edildikten sonra anestezi verilmesini takiben ekssanguinasyon yöntemiyle sakrifiye edildi, toraks ön duvarı açıldı, kalp içerisinden enjektör yardımıyla 5 cc kan alınarak biyokimyasal analizler yapıldı, toplanan kan örneklerinde proanjiyogenik faktörlerden vasküler endotel büyüme faktörü ve anjiopoietin-1, anti-anjiyogenik faktörlerden endostatin ve anjiostatinin serumdaki düzeyleri ölçüldü. Ratların arka bacaklarından gastroknemius kasları çıkarılarak histopatolojik analizler yapıldı, alınan kas dokusu örnekleri ışık ve elektron mikroskobisi ile değerlendirildi. Bulgular: Yapılan değerlendirmeler sonucunda, lipoteikoik asit grubunda diğer gruplara göre yeni oluşan kapillerite sayısı, anjiopoietin-1 düzeyi, endostatin ve anjiostatin bakımından anlamlı derecede artış tespit edildi (p<0.05). Sonuç: Bulgularımız, kronik iskemi modelinde lipoteikoik asitin anjiyogenezisi etkin bir biçimde sağladığını, aynı zamanda proanjiyogenik ve anti-anjiyogenik sitokinlerin her ikisinde birden artışa yol açarak anjiyogenezisin kontrollü bir süreçte geliştiğini telkin etmektedir.

Endometrial cancer is the most common cancer of the female reproductive system. Perifosine has shown anti-tumor activity in a variety of cancers by inhibition of AKT phosphorylation. The active metabolite of vitamin D (1,25(OH)2D3) has anti-proliferative and pro-apoptotic properties and is recognized as an agent with the great potential for cancer intervention. Combination treatment with specific agents has been widely used as targeted therapy for cancer. In this study, we aimed to investigate the anti-apoptotic effect of varying concentrations of perifosine and vitamin D on endometrial cancer cell line (HEC1A). The expression levels of P53, BCL2 and BAX were assessed in cultured HEC1A cells at 10 and 30 μM concentrations of perifosine, 50 and 200 nM of vitamin D and combination groups using qRT PCR. Apoptosis evaluation in HEC-1A cells was performed using flow cytometry after 48 and 72 h of treatment with perifosine, vitamin D and combinations of both. According to the obtained data, treatment with different doses of perifosine and vitamin D significantly induced apoptosis in a time and dose-dependent manner in HEC-1A cells. The mRNA expression levels of P53, BAX, BCL2 in HEC-1A cells were found to be significant in the experimental groups as compared with the control. Perifosine displayed substantial anti-tumor activity in HEC-1A. These effects were increased with vitamin D. Therefore, perifosine and vitamin D combinations should be further evaluated in clinical studies in endometrial cancer.

The nervous system is an important target of radiofrequency (RF) radiation exposure since it is the excitable component that is potentially able to interact with electromagnetic fields. The present study was designed to investigate the effects of 1,800 MHz RF radiation and the protective role of paricalcitol on the rat sciatic nerve. Rats were divided into four groups as control, paricalcitol, RF, and RF + paricalcitol. In RF groups, the rats were exposed to 1,800 MHz RF for 1 h per day for 4 weeks. Control and paricalcitol rats were kept under the same conditions without RF application. In paricalcitol groups, the rats were given 0.2 μg/kg/day paricalcitol, three times per week for 4 weeks. Amplitude and latency of nerve compound action potentials, catalase activities, malondialdehyde (MDA) levels, and ultrastructural changes of sciatic nerve were evaluated. In the RF group, a significant reduction in amplitude, prolongation in latency, an increase in the MDA level, and an increase in catalase activity and degeneration in the myelinated nerve fibers were observed. The electrophysiological and histological findings were consistent with neuropathy, and the neuropathic changes were partially ameliorated with paricalcitol administration. Bioelectromagnetics. 39:631–643, 2018.