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[ntroduction] Valosin-containing protein (VCP) disease, caused by mutations in the VCP gene, results in myopathy, Paget's disease of bone (PBD) and frontotemporal dementia (FTD). Natural history and genotype-phenotype correlation data are limited. This study characterises patients with mutations in VCP gene and investigates genotype-phenotype correlations., [Methods] Descriptive retrospective study collecting clinical and genetic data from patients with confirmed mutations in the VCP gene in 52 centres from 24 countries., [Results] We included 234 patients (70% males, mean age 55.54 + 9.6 years [y]). Mean age at symptom onset 45.6 + 9.3 y, mean diagnostic delay 7.74 + 6 y, and mean time of disease progression 11.3 + 6.9 y. Disease onset was symmetric lower limb weakness in 50% of the patients progressing towards generalized muscle weakness affecting proximal and distal lower and upper limb muscles. Other clinical features included: respiratory symptoms in 40.3%, PBD in 26.7%, dysautonomia in 21.4%, upper and lower motor neuron signs in 13.3% and 21.85%, and FTD in 13.9% of the patient. Fifty-eight genetic variants were identified being the most frequent the c.464G>A, p.Arg155His in 28% of the patients and the c.463C>T, p.Arg155Cys in 11.1%. Twenty new mutations were identified. The c.463C>T, p.Arg155Cys variant had the earliest age of onset (37.8 + 7.6 y) among the 4 most frequent variants and a higher frequency of axial weakness, distal upper limb weakness, scapula winging and mix cognitive. 19.1% of the patients were full time wheelchair users and 4.0% (9/225) were bedridden at a median of 8.5 y and 15 y from onset. Thirty–seven patients died at a mean age of 63.9 + 8.1 and at a mean of 15.8 + 6.6 y from disease onset, 7 due to respiratory insufficiency and 5 due to rapidly progressive dementia. The presence of a FVC< 50% was associated with being full time wheelchair user/ bedridden and the presence of a FVC, [Conclusion] The heterogeneous clinical features of VCP could resemble other neuromuscular conditions. The c.463C>T p.Arg155Cys variant seems to have an earlier age of onset and more severe phenotype. Presence of FVC

Purpose: Paracetamol has been shown to exert anxiolytic-like effects mediated by endocannabinoids via cannabinoid CB1 receptors. Dipyrone is an analgesic with similar effects to paracetamol rather than non-steroidal anti-inflammatory drugs. Involvement of central structures to its effects are long under debate, whereas recent findings suggesting contribution of cannabinoid CB1 receptors to its antinociceptive effect support this argument. Taken together, the purpose of this study was to investigate whether dipyrone possesses anxiolytic-like behavior; contribution of cannabinoid CB1 and CB2 receptors and TRPV1 receptors will be determined in case of observing any effect of dipyrone in anxiety tests. Material and Methods: Balb-c mice effects of dipyrone (150, 300, 600 mg/kg, i.p.) were assessed in three-chamber social interaction, open-field, elevated plus-maze and rota rod tests. The cannabinoid CB1 antagonist AM251 (1 mg/kg i.p.), the CB2 antagonist SR 144528 (1 mg/kg i.p.) and the TRPV1 antagonist capsazepine (3 mg/kg i.p.) were going to be administered before dipyrone injections if any effect of dipyrone occurs. Results: Dipyrone had no effect at any dose in behavioral tests (three-chamber social interaction, open-field, elevated plus-maze and rota rod tests). Therefore, dipyrone is not tested together with the cannabinoid CB1 and CB2 antagonists and the TRPV1 receptor antagonist. Conclusion: Unlike paracetamol, dipyrone did not possess anxiolytic-like effects in mice. Discrepancies in experimental models and methodologies may be the reason of our results.

Non-steroidal anti-inflammatory drugs produce antinociceptive effects mainly through peripheral cyclooxygenase inhibition. In opposition to the classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone exert weak anti-inflammatory activity, their antinociceptive effects appearing to be mostly due to mechanisms other than peripheral cyclooxygenase inhibition. In this review, we classify classical non-steroidal anti-inflammatory drugs, paracetamol and dipyrone as “non-opioid analgesics” and discuss the mechanisms mediating participation of the endocannabinoid system in their antinociceptive effects. Non-opioid analgesics and their metabolites may activate cannabinoid receptors, as well as elevate endocannabinoid levels through different mechanisms: reduction of endocannabinoid degradation via fatty acid amide hydrolase and/or cyclooxygenase-2 inhibition, mobilization of arachidonic acid for the biosynthesis of endocannabinoids due to cyclooxygenase inhibition, inhibition of endocannabinoid cellular uptake directly or through the inhibition of nitric oxide synthase production, and induction of endocannabinoid release.

Vibration analysis of rods that are subjected to rotation is presented. It is shown that flexural-flexural, longitudinal-flexural and torsional-flexural wave coupling occur due to the Coriolis Effect. First, we carried out our analysis for thin rods where the wavelength is much larger than the radius. It is shown that the wavenumbers change due to the Coriolis Effect. Then, we characterize the 3-D wave propagation in rotating rods by using the Finite Element Method (FEM) in order to determine the corresponding wavenumber shifts for each type of wave. We show that for different drive frequency (omega(0)) and rotation rate (Omega), wave couplings exhibit different characteristics. For flexural-flexural wave coupling, the wavenumber increases for the primary flexural wave whereas the wave number decreases for the coupled flexural wave where Omega < omega(0). For the Coriolis coupling between flexural-longitudinal waves, the wavenumber increases for the flexural wave and decreases for the longitudinal wave where Omega < omega(0). For the Coriolis coupling between flexural-torsional waves, the wavenumber increases for both flexural and torsional waves. (C) 2020 Elsevier Ltd. All rights reserved.

Objective: The effects of antipsychotic drugs, of whose different classes can be used in the treatment of patients with resistant to schizophrenia, on the fetus and the benefits of the treatment to the mother should be taken into consideration before making a decision about initiating treatment. This study aimed to examine the effects of prenatal exposure to various antipsychotic agents on learning and memory in adult rats.Method: In this study, antipsychotic drugs from different chemical classes (2 mg/kg haloperidol, 100 mg/kg thioridazine, 200 mg/kg sulpiride, 20 mg/kg chlorprothixene, 40 mg/kg clozapine, 10 mg/kg fluphenazine, 20 mg/kg chlorpromazine) and water for the control group were administered to pregnant Sprague-Dawley dams through gavage during the pregnancy period. In total, 16 groups were created and tested in the Morris water maze by dividing offspring of eight mother rats into male and female rat groups (n=10) on postpartum day 60. Learning was tested with hidden platform task and ...

Glutamate is believed to be the predominant excitatory neurotransmitter in the networks responsible for itch-related behavior. Beta-lactam antibiotics were shown to exert neuroprotective effects by increasing expression of the glutamate transporter GLT-1. We observed whether repeated administration of the beta-lactam antibiotic ceftriaxone suppresses serotonin-induced itch-related behavior (similarly to its effect on pain transmission) in mice. Chronic, but not acute, ceftriaxone introductions reduced the number of serotonin-induced scratches; dihydrokainic acid, a selective GLT-1 transporter inhibitor, partly but significantly abolished this effect of ceftriaxone. Our findings suggest that GLT-1 activation by beta-lactam antibiotics looks promising for the treatment of chronic itch. Як вважають, глутамат є основним збуджуючим нейротрансмітером у нейронних мережах, відповідальних за поведінкові моторні прояви при почутті свербіжу. β-лактамні антибіотики мають нейропротективні властивості, оскільки забезпечують посилену експресію глутаматного транспортера GLT-1. Ми з’ясовували, чи здатне повторне введення β-лактамного антибіотика цефтриаксону пригнічувати викликані ін’єкціями серотоніну поведінкові моторні прояви (чухальні рухи), пов’язані з індукцією почуття свербіжу (подібно до впливу цього агента на біль) у мишей. Хронічні (але не поодинокі) введення цефтриаксону викликали зменшення кількості рухів чухання. Селективний блокатор транспортера GLT-1 дигідрокаїнова кислота частково, але істотно перешкоджала цьому ефекту цефтриаксону. Наші спостереження дають підстави вважати, що активація GLT-1 β-лактамними антибіотиками є перспективним підходом у лікуванні хронічного свербіжу.

Objective: The aim of the study was to determine the protective effect of curcumin against ionizing radiation-induced cataract in the lens of rats. Material and Methods: Rats were divided into six groups. Group 1: Control, Group 2: Dimethyl sulfoxide (DMSO), Group 3: DMSO+curcumin, Group 4: Irradiation, Group 5: Irradiation+DMSO, Group 6: Irradiation+DMSO+curcumin. A 15 Gy total dose was given to 4, 5, 6 groups for radiation damage. Curcumin (100 mg/kg) was dissolved in DMSO and given by intragastric intubation for 28 days. At the end of the experiment, lenses were graded and enucleated. The lenticular activity of the antioxidant enzymes, total antioxidant and glutathione peroxidase (GSH-Px), and the malondialdehyde (MDA) were measured. Results: 100% Cataract was seen in the irradiation group. Cataract rate fell to 40% and was limited at grade 1 and 2 in the curcumin group. In the irradiation group, antioxidant enzyme levels were decreased, MDA levels were increased. There was an increase in antioxidant enzyme levels and a significant decrease in MDA in the group which was given curcumin. Conclusion: Curcumin has antioxidant and radioprotective properties and is likely to be a valuable agent for protection against ionizing radiation. Hence, it may be used as an antioxidant and radioprotector against radiation-induced cataractogenesis. Turkish Başlık: Sıçanlarda İyonizan Radyasyonla Oluşturulan Katarakt Üzerine Curcuminin Koruyucu Etkisi Anahtar Kelimeler: Katarakt, curcumin, iyonizan radyasyon, lipid peroksidasyonu, oksidatif stres, radioprotektif Amaç: Çalışmamızın amacı, sıçan lenslerinde iyonizan radyasyonla oluşturulan katarakt modelinde curcuminin koruyucu etkisini incelemektir. Gereç ve Yöntemler: Sıçanlar altı gruba ayrıldı. Grup 1: Kontrol, Grup 2: Dimetil sülfoksid (DMSO), Grup 3: DMSO+curcumin, Grup 4: Radyasyon, Grup 5: Radyasyon+DMSO, Grup 6: Radyasyon+DMSO+curcumin. Grup 4, 5 ve 6'ya hasar oluşturmak için iyonizan radyasyon toplam 15 Gy dozunda verildi. Curcumin (100 mg/kg), DMSO içinde çözülerek 28 gün süresince intragastrik yoldan verildi. Çalışmanın sonunda, lensler sınıflandırıldı ve çıkarıldı. Lens dokusunda antioksidan durumu değerlendirmek üzere total antioksidan, glutatyon peroksidaz (GSH-Px) enzimleri ve oksidan durumu değerlendirmek üzere malondialdehit (MDA) düzeylerine bakıldı. Bulgular: Radyasyon alan grupta %100 katarakt görüldü. Curcumin verilen grupta bu oran %40'a düştü ve grade 1 ve 2 ile sınırlıydı. Radyasyon alan grupta, kontrol grubuna göre antioxidan enzim seviyesi düştü, MDA enzim seviyesi yükseldi. Curcumin verilen grupta radyasyon grubuna göre ise anlamlı şekilde antioxidan enzim seviyesi yükseldi, MDA enzim seviyesi düştü. Sonuç: Curcumin antioksidan ve radioprotektif özelliklere sahiptir ve iyonizan radyasyona karşı koruyucu olarak değerli bir ajan olması nedeni ile antioksidan ve radioprotektör olarak radyasyon nedenli katarakt oluşumunda kullanılması önerilebilir.

At the high level, the Internet is a mesh that is composed of thousands of autonomous system (AS) connected together. This mesh is represented as a graph where each autonomous system is considered as a node and the connections with Border Gateway Protocol neighbored autonomous systems considered as an edge. Analysis of this mesh and visual representation of the graph gives us the AS level topology of the Internet. In recent years there are increasing numbers of studies that are focused on the structure of the topology of the Internet. It is important to study the Internet infrastructure in Turkey and to provide a way to monitor the changes to it over time. In this study we present the AS level Internet map of Turkey with explanation of each step. In order to get the whole AS level map, we first determined the ASs that geographically reside in Turkey and afterwards determined the interconnections among this ASs, along with international interconnections. Then we extracted the relations between connected ASs and analyzed the structural properties of AS infrastructure. We explained the methods we used in each step. Using the extracted data we analyzed the AS level properties of Turkey and we provide the AS level Internet map of Turkey along with a web-based software that can monitor and provide information of ASs in Turkey., İnternet, üst seviyede incelendiğinde, Otonom Sistem (OS) olarak temsil edilen binlerce ağın birbirine bağlandığı, dünyayı saran her OS'nin bir düğüm ve Border Gateway Protokolü komşuluğu olan diğer OS'ler ile birleşmesinin bir link olarak kabul edildiği örgüdür. Bu örgünün incelenmesi ve grafiğe dönüştürülmesi, İnternet'in otonom sistem seviyesindeki topolojisini verir. İnternet topolojisi üzerinde yapılan çalışmalar son yıllarda ivme kazanmıştır. İnternet altyapısı üzerinde araştırma yapılması ve düzenli takip edilen bir sistemin geliştirilmesi gerekmektedir. Bu çalışmada Türkiye'de bulunan OS'lerin bağlantı haritası çıkarılması adım adım aşamaları ile birlikte sunulmaktadır. Yapılan çalışmada öncelikle Türkiye'de bulunan OS'ler tespit edilmiş ve bu OS'ler arasındaki bağlantı yurtdışı uluslar arası bağlantıları ile birlikte elde edilmiştir. Tespit edilen OS'ler arası ilişkiler ortaya konularak, Türkiye'nin internet altyapısının yapısal özellikleri belirlenmiş ve bunlar belirlenirken kullanılan metotlar ortaya konulmuştur. Yapılan bu çalışmalar doğrultusunda çeşitli analizler yapılmış, hazırlanan yazılım ile Türkiye'nin otonom sistem seviyesindeki internet topolojisi çıkarılmıştır.

At the end of the last year, we, editorial team, decided to redesign our website to better serve our readers, reviewers and authors. After much hard work, we are excited to officially announce the new and improved Balkan Medical Journal website. You can now reach us at http://balkanmedicaljournal.org/ We thought that it was important to renew the website to reacha wider audience. So, we wanted to have good, clear, easy-tofollow navigation throughout our website. The new website will remain both open access and free of article processing charges.We hope that the website will respond better to our readers'needs and interests.

We have shown that morphine has an anticonvulsive effect against maximal electroconvulsive shock (MES) in mice, and this effect is antagonized by histamine H1-receptor antagonists. Brain histamine is localized both in neurons and in mast cells, and morphine is known to enhance the turnover of neuronal histamine and to release histamine from mast cells. In the present experiments, compound 48/80 was injected chronically (0.5 mg/kg on day 1, 1 mg/kg on day 2, 2 mg/kg on day 3, 3 mg/kg on day 4, and 4 mg/kg on day 5, twice daily, ip) to deplete mast cell contents. Morphine (0.001-10 mg/kg, ip; N = 20) produced a dose-dependent anticonvulsive effect against MES seizure in mice with non-depleted mast cells, whereas it did not exert any anticonvulsive effect in mice with depleted mast cells. These results indicate that morphine produces its anticonvulsive effect against maximal electroconvulsive shock in mice by liberating histamine from mast cells.

Morphine is known to release histamine from mast cells. It is also known that histamine receptors mediate some of morphine's effects on the central nervous system. The contribution of H1- and H2-receptors to the effect of morphine on maximal electroconvulsive shock in mice was investigated in the present experiments. Morphine showed a dose-dependent anticonvulsive effect, but produced spontaneous clonic convulsions at higher doses (100 mg/kg, i.p.). The anticonvulsive effect of morphine (1 mg/kg, i.p.) was antagonized by histamine H1-receptor antagonists, dimethindene (0.1 mg/kg, i.p.) promethazine (0.4 mg/kg, i.p.) and pheniramine (30 mg/kg, i.p.), and naloxone (10 mg/kg, i.p.), but not by the H2-receptor antagonist ranitidine (10-50 micrograms, i.c.v.). These results show that morphine has an anticonvulsive effect via histamine H1-receptors against maximal electroconvulsive shock in mice.

Objective: The increase in symmetric (SDMA) and asymmetric dimethyl arginine (ADMA) is associated with endothelial dysfunction. The aim of this study was to evaluate the effect of exercise on ADMA and SDMA levels and related ratios in type 2 DM. Material and Methods: Thirty-six women with type 2 DM and 44 healthy women were recruited to the study. Fourteen and 19 subjects, respectively, attended four-weeks of moderate intensity exercise. Plasma SDMA, ADMA, and L-arginine levels were measured by the HPLC method initially, after the first exercise session, and after one month. Results: All measurements were within the normal range in both groups and did not change significantly immediately after exercise and after the first month. In the healthy group, L-arginine/ADMA and L-arginine/SDMA ratios after one month were significantly higher than the initial values (p

Objective: The aim of this study is to evaluate the efficacy of dipyridamole in relieving the vasospasm of coronary artery bypass grafts. Material and Methods: Twenty two patients who underwent elective coronary artery bypass grafting (CABG) were admitted to the study (Men/Women: 14/8, mean age: 62.4±8.8 years). Ten samples from left internal mammary(LIMA), radial arterial (RA) and saphenous vein (SV) grafts were collected for each. The samples were transported to the vascular laboratory in 4°C Krebs solution. Submaximal smooth muscle contraction was achieved first by 10-7M of phenylephrine solution. Dipyridamole was then added, starting from a concentration of 10-9M to a concentration of 10-3.5M in two minutes intervals and half logarithmic dose increments. The concentration-response curves were obtained of the vasodilatation response relative to the begining. Results: In the LIMA graft samples, the vasodilation response to dipyridamole was 43.2±1.6% and 97.6±4.1% at concentrations of 10-6M and 10-3.5M respectively. In RA graft samples, the vasodilation response to dipyridamole was 36.3±1.8% and 95.3± 2.7% at concentrations of 10-6M and 10-3.5M respectively. In SV graft samples, however, the vasodilation response to dipyridamole was 43.2±1.4 % and 96.6± 2.2% at concentrations of 10-6M and 10-3.5M respectively. Conclusions: The amplitude of relaxation response to dipyridamole of all grafts samples were similar, without statistically significant difference among the IMA, RA and SV grafts in the in vitro tissue bath system. These results prove that dipyridamole has a potential use as a vasodilatatory drug in all graft types.

Amaç: Tip 2 diyabetik hastaların birinci derece yakınlarında, ailesinde diyabet öyküsü olmayan sağlıklı olgulara göre kardiyovasküler hastalıklar daha sık görülmektedir. Asimetrik dimetilarginin (ADMA) ve homosistein (Hcy) plazma düzeyleri kardiyovasküler hastalıklar ve endotel disfonksiyonuyla ilişkili göstergelerdir. Bu çalışmada, tip 2 diyabetik hastaların birinci derece yakınlarında ADMA ve Hcy plazma düzeyleri ile bu göstergelerle kardiyovasküler risk faktörleri arasındaki ilişkilerin incelenmesi amaçlandı. Hastalar ve Yöntemler: Dolaşımdaki ADMA ve Hcy düzeyleri 15 tip 2 diyabet hastasının birinci derece yakınında ve ailesinde diyabet öyküsü olmayan 15 kontrol olgusunda ölçüldü. Bulgular: Her iki grup arasında ADMA ve Hcy plazma düzeyleri açısından anlamlı farklılık saptanmadı (p>0.05). Asimetrik dimetilarginin plazma düzeyi tip 2 diyabetik olguların birinci derece yakınlarında, bel çevresi (p=0.02), açlık insülin düzeyi (p=0.03), insülin direnci (p=0.01), total kolesterol (p=0.04) ve HDL kolesterol (p=0.03) ile ilişkiliydi. Sonuç: Bu sonuçlara göre, kardiyovasküler risk faktörlerine sahip olan tip 2 diyabetik olguların birinci derece yakınlarında, ADMA plazma düzeylerinin doğrudan endotel disfonksiyonunun gelişimine katkıda bulunmadığını düşünmekteyiz. Objectives: Cardiovascular diseases are more common among first degree relatives of type 2 diabetic patients than healthy subjects without a family history of diabetes. Plasma asymmetric dimethylarginine (ADMA) and homocysteine (Hcy) levels are markers of endothelial dysfunction and cardiovascular disease. The objective of this study was to evaluate levels of ADMA, Hcy and their association with cardiovascular risk factors in first degree relatives of type 2 diabetic patients. Patients and Methods: The circulating ADMA and Hcy levels were measured in 15 first degree relatives of type 2 diabetic patients and 15 control subjects without a known family history of diabetes. Results: No statistically significant differences were found in plasma levels of ADMA and Hcy between the two groups (p>0.05). Plasma ADMA levels correlated significantly with waist circumference (p=0.02), fasting insulin levels (p=0.03), insulin resistance (p=0.01), total cholesterol (p=0.04) and HDL-cholesterol (p=0.03) levels in the first degree relatives of type 2 diabetic patients. Conclusion: These results suggest that plasma ADMA levels do not directly contribute to the development of endothelial dysfunction in first degree relatives of type 2 diabetic patients with cardiovascular risk factors.