Prevention of epidural fibrosis in rats by local or systemic administration of citicoline

AIM: The objective of this study was to investigate the effect of citicoline administration on epidural fibrosis which is a frequent complication of lumbar disc surgery with no effective treatment or preventive surgical technique. MATERIAL and METHODS: Sixty Sprague-Dawley female rats undergoing L4-5 right hemilaminotomy and annular fenestration were arranged in three groups: rats in Group 1 (control group) and Group 2 (topical citicoline group) were applied 0,9% saline and 100 mu M citicoline on surgical area, respectively, while rats in Group 3 (systemic citicoline group) received 600 mu mol/kg citicoline intraperitoneally. Rats were sacrificed four weeks later and their vertebral colons were removed en bloc. Groups were evaluated according to histological criteria and results were compared using statistical tools. RESULTS: Compared with control group, significantly less epidural fibrosis, dural adhesion, fibroblast cell density, foreign body reaction, and medulla spinalis retraction were observed in groups treated with topical and systemic citicoline (groups 2 and 3) (p 0,05). CONCLUSION: Our study demonstrates for the first time in the literature that citicoline may be effective for preventing postoperative epidural fibrosis. However, its mechanism of action and clinical effectiveness must be further investigated

Kolin’in Merkezi ve Periferik Kolinerjik Nöronlarda ve Kolinerjik İletimdeki İşlevi

Kolin bir kuaterner amin olup, nörotrasmitter asetilkolinin ve membranın temel yapılarından fosfotidilkolin’in öncül maddesidir. Kolin ayrıca vücutta, metionin ve s-adenosilmetionin rejenerasyonu için gerekli metil guruplarının vericisi olan, betaine de metabolize olur. Bu derlemede esas olarak kolin’in cholinergic noronal görevlerindeki rolü üzerinde durulacaktır. Kolinerjik nöronların asetilkolin sentezi için kulandıkları kolin esas olarak kaynağı dolaşımdır. Dolaşımdaki kolin’in düzeyi 6-8 saatlik açlık sonrası 10 μM kadardır. Bu düzey yemek sonrası, gıdalardaki kolin‘in miktarına göre, 20-60 μM kadar yükselebilir. Farmakolojik dozlarda tedavi ile de kan kolin düzeyi 200-300 μM kadar yükselebilir. Kolin’i asetilkoline dönüştüren enzim kolinasetiltrasferaz enzimi substratı kolini zayıf bir şekilde doyurulmuş olduğundan plazmada kolin düzeyinin yükselmesi asetilkolin sentezini arttırır. Kolin, yeterince yüksek düzeylerinde (0,5-100 mM gibi), muskarinik ve nikotinik asetikolin reseptörleri ile agonist olarak da etkileşir. Kolin tedavisi nörotrasmitter asetilkolin’in sentez ve salıverilmesinde hızlanma ve merkezi ve periferik muskarinik ve nikotinik kolinerjik iletide yükselme ile sonuçlanır. Kolin, burada tartışılacak olan, kolinerjik nitelikte birçok fizyolojik, farmakolojik ve nörokimyasal etkiler oluşturur

Cytidine and Uridine Increase Striatal CDP-Choline Levels Without Decreasing Acetylcholine Synthesis or Release

SUMMARY Aims: Treatments that increase acetylcholine release from brain slices decrease the synthesis of phosphatidylcholine by, and its levels in, the slices. We examined whether adding cytidine or uridine to the slice medium, which increases the utilization of choline to form phospholipids, also decreases acetylcholine levels and release. Methods: We incubated rat brain slices with or without cytidine or uridine (both 25-400 µM), and with or without choline (20-40 µM), and measured the spontaneous and potassium-evoked release of acetylcholine. Results: Striatal slices stimulated for 2 h released 2650 ± 365 pmol of acetylcholine per mg protein when incubated without choline, or 4600 ± 450 pmol/mg protein acetylcholine when incubated with choline (20 µM). Adding cytidine or uridine (both 25-400 µM) to the media failed to affect acetylcholine release whether or not choline was also added, even though the pyrimidines (400 µM) did enhance choline`s utilization to form CDP-choline by 89 or 61%, respectively. The pyrimidines also had no effect on acetylcholine release from hippocampal and cortical slices. Cytidine or uridine also failed to affect acetylcholine levels in striatal slices, nor choline transport into striatal synaptosomes. Conclusion: These data show that cytidine and uridine can stimulate brain phosphatide synthesis without diminishing acetylcholine synthesis or release

Changes in serum proteins after endotoxin administration in healthy and choline-treated calves

Background: This study aimed to investigate the possible serum protein changes after endotoxin administration in healthy and choline-treated calves using proteomics. These results are expected to contribute to the understanding of the pathophysiological mechanisms of endotoxemia and the beneficial effect of choline administration in this clinical situation. Methods: Healthy-calves (n = 20) were divided into 4 groups: Control, Choline treated (C), Lipopolysaccharide administered (LPS), and LPS + C. Control calves received 0.9 % NaCl injection. Calves in C and LPS + C groups received choline chloride (1 mg/kg/iv). Endotoxin (LPS) was injected (2 mu g/kg/iv) to the calves in LPS and LPS + C groups. Serum samples were collected before and after the treatments. Differentially expressed proteins (> 1.5 fold-change relative to controls) were identified by LC-MS/MS. Results: After LPS administration, 14 proteins increased, and 13 proteins decreased within 48 h as compared to controls. In the LPS group, there were significant increases in serum levels of ragulator complex protein (189-fold) and galectin-3-binding protein (10-fold), but transcription factor MafF and corticosteroid binding globulin were down regulated (>= 5 fold). As compared with the LPS group, in LPS + C group, fibrinogen gamma-B-chain and antithrombin were up-regulated, while hemopexin and histone H4 were down-regulated. Choline treatment attenuated actin alpha cardiac muscle-1 overexpression after LPS. Conclusions: LPS administration produces changes in serum proteins associated with lipid metabolism, immune and inflammatory response, protein binding/transport, cell adhesion, venous thrombosis, cardiac contractility and blood coagulation. The administration of choline is associated with changes in proteins which can be related with its beneficial effect in this clinical situation

Prognostic significance of survivin, β-catenin and p53 expression in urothelial carcinoma

Survivin, β-catenin, and p53 are well-known cell-cycle and apoptosis regulators of tumorigenesis. Urothelial carcinomas (UCs) are the most common of the human cancers. Compared to superficial tumors (Ta, CIS, or T1), invasive UCs are important with regard to recurrence, progression, and mortality. Therefore, we examined whether survivin, β-catenin, and p53 could be used as the biomarkers for the early prediction of the invasiveness of UCs and the overall survival of the patients. We investigated the prognostic expressions of those biomarkers in UC (n=147) and in non-muscle invasive UC (NMI-UC) (n=113), using tissue microarray and immunohistochemistry. Spearman's correlation analysis and multivariate Cox regression analyses were used for statistical interpretation. High expressions of β-catenin, survivin, and p53 were associated with a high T stage, recurrence, progression, mortality, low recurrence-free survival, low progression-free survival and low overall survival (p < 0.01). Similar findings were achieved for recurrence and progression in the NMI-UC group, except for mortality. Moreover, a positive correlation was shown between p53 and β-catenin and between p53 and survivin (r=0.221, p < 0.01; r=0.236, p < 0.01, respectively). Survivin, p53, and β-catenin overexpression, as prognostic markers, might suggest that the UCs are biologically aggressive with the poor prognosis. Thus, dysregulation of those these cell-cycle and apoptosis regulators in bladder carcinoma could be used as a molecular marker to determine the best treatment strategy and could contribute to the development of targeted therapies

Real-world efficacy and safety of Ledipasvir plus Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir +/- Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience

Background/Aims: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population.Material and Methods: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)+/- ribavirin (RBV) ombitasvir/paritaprevir/ritonavir +/- dasabuvir (PrOD)+/- RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed.Results: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90 +/- 54.60 U/L to 17.00 +/- 14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51 +/- 4.54 to 7.32 +/- 3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0 +/- 16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%).Conclusion: LDV/SOF or PrOD +/- RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.Turkish Association for the Study of The Liver (TASL

Elektrikle Uyarılmanın ve K + Depolarizasyonunun Sıçan Striatal Dilimlerinde Asetilkolin ve Kolin Salıverilmesine ve Doku Düzeylerine Etkisi

Amaç: Elektrikle ya da yüksek potasyumla uzun süreli uyarılmanın sıçan striatal beyin dilimlerinde asetilkolin ve kolin metabolizmasına etkilerini belirlemek. Yöntemler: Striatal dilimler dinlenme durumunda, elektrikle uyarılarak ya da yüksek potasyumla depolarize edilerek 120-dakika perfüze edildi. Perfüzatta ve dokudaki asetilkolin ve kolin radioenzimatik yöntemle ölçüldü. Bulgular: Dinlenme koşullarındaki dilimlerden ortama 376±20 pmol/mg protein/120 dakika asetilkolin ve 2375±85 pmol/mg protein/120 dakika kolin salıverildi. Uyarılma ile asetilkolin salıverilmesi 5-6 kat artarak elektrikle uyarılmada 2830±174 pmol/mg protein/120 dakika, potasyumla depolarizasyonda ise, 2360±85 pmol/mg protein/120 dakika düzeyine ulaştı. Kolin salıverilmesi elektrikle uyarımda değişmedi. Potasyumla depolarizasyonda ise, kolin çıkışı ilk 20 dakikalık dönemde %50 artmakla (p<0,01) beraber, 120 dakikalık dönemin toplamında %25 kadar azaldı (p<0,05). Bazal koşullarda perfüzyon ile doku asetilkolin ve kolin düzeyleri değişmedi. Elektrikle uyarılma doku kolin düzeyi değişmedi. Doku asetilkolin düzeyinde ise sınırlı (%20; 485±25 pmol, P<0,05) bir azalma oldu. Potasyumla depolarizasyonda dokudan asetilkolin kaybı (1800±85 pmol/mg protein) ve kolin kaybı (602±28 pmol/mg protein) daha yüksekti. Dinlenmede şartlarında tutulan, elektrikle uyarılan ya da potasyumla depolarize edilen dilimler 120 dakikalık sürede, sırayla, 390±21, 2345±165 (p<0,001) ya da 960±65 (p<0,001) pmol/mg protein asetilkolin ve 2335±170, 2203±95 ya da 1241±105 pmol/mg (p<0,001) kolin sentez etti. Toplam kolin oluşumu (asetilkolin+kolin) bazala göre elektrikle uyarılma ile %60 arttı (p<0,001). Potasyumla depolarizasyonda ise, %25 baskılandı (p<0,05). Sonuçlar: Bu bulgular elektrikle ve yüksek potasyumla uyarılmanın striatal dilimlerde asetilkolin ve kolin metabolizmasını farklı bir şekilde etkilediğini göstermektedir. Elektrikle uyarılma asetilkolin sentez ve salıverilmesini ve dokuda kolin oluşumunu arttırmaktadır. Potasyumla depolarizyonda ise asetilkolin sentez ve salıverilmesi artarken yeni kolin oluşumu baskılanmaktadır