Nanočestice L-glutaminske kiseline-g-polihidroksietilnoga metakrilata – akutna i subakutna toksičnost i bioraspodjela u miševa

The aim of this safety study in mice was to determine in vivo toxicity and biodistribution potential of a single and multiple doses of L-glutamic acid-g-p(HEMA) polymeric nanoparticles as a drug delivery system. The single dose did not cause any lethal effect, and its acute oral LD50 was >2.000 mg/kg body weight (bw). Multiple doses (25, 50, or 100 mg/kg bw) given over 28 days resulted in no significant differences in body and relative organ weights compared to control. These results are supported by biochemical and histological findings. Moreover, nanoparticle exposure did not result in statistically significant differences in micronucleus counts in bone marrow cells compared to control. Nanoparticle distribution was time-dependent, and they reached the organs and even bone marrow by hour 6, as established by ex vivo imaging with the IVIS® spectrum imaging system. In conclusion, L-glutamic acid-g-p(HEMA) polymeric nanoparticles appear biocompatible and have a potential use as a drug delivery system.Cilj je ovoga istraživanja bio utvrditi in vivo toksičnost i raspodjelu jednokratne i višekratnih doza polimernih nanočestica L-glutaminske kiseline-g-p(HEMA) u funkciji isporuke lijekova. Jednokratna oralna doza nije prouzročila smrtnost, a akutni LD50 iznosio je >2,000 mg/kg tjelesne težine. Višekratne oralne dnevne doze od 25 mg, 50 mg i 100 mg/kg tjelesne težine, davane 28 dana, nisu dovele do značajnih razlika u ukupnoj tjelesnoj i relativnoj težini organa u usporedbi s kontrolnom skupinom. Ove rezultate potvrđuju biokemijski i histološki nalazi. Izloženost nanočesticama nije uzrokovala statistički značajne razlike u broju mikronukleusa u stanicama koštane srži miševa u odnosu na kontrolu. Raspodjela nanočestica u tijelu mijenjala se s vremenom, a nanočestice bi doprle u organe, pa i u koštanu srž, unutar prvih šest sati od primitka doze, što je utvrđeno ex vivo snimkama dobivenim pomoću sustava IVIS® Spectrum. Naši rezultati upućuju na to da su polimerne nanočestice L-glutaminske kiseline-g-p(HEMA) biokompatibilne i imaju potencijala za primjenu kao sustav isporuke lijekova

Repression of the Notch pathway prevents liver damage in streptozotocin-induced diabetic mice

Introduction. Sunitinib is an oral inhibitor of vascular endothelial growth factor that is used to treat a variety of cancer. There are limited data regarding the effect of sunitinib on diabetes. In the liver, Notch signaling plays an important role in liver tissue development and homeostasis and its dysfunction is associated with liver pathol­ogies. The aim of the present study is to investigate the effects of sunitinib on streptozotocin (STZ)-induced diabetic liver in mice models. Material and methods. An experimental diabetes mellitus (DM) model was created in 28 male CD-1 mice. Twenty-eight male CD-1 mice divided in four groups (n = 7 each) were used; control mice (C), control mice treated with sunitinib (C + S), diabetic mice (DM), and diabetic mice treated with sunitinib (DM + S) for four weeks. The histopathological changes in the liver were examined by histochemistry and immunohistochemistry. Immunoreactivity of Notch1, Jagged1, DLL-1 and VEGF were evaluated in control and diabetic mice after sunitinib treatment. Results. The significant morphological changes in the liver were mostly seen in hepatocytes that were hyper­trophied in the DM mice, with an increased amount of eosinophilic granules; moreover, some hepatocytes contained empty vacuole-like structures. The livers of the DM mice revealed increased deposition of collagen fibers. After sunitinib treatment the hepatocytes and hepatic lobules had almost similar morphology to control mice. The immunoreactivities of Notch1, Jagged1, DLL-1 and VEGF in hepatocytes were significantly lower in the DM group when compared with the C, DM + S and C + S group treated with sunitinib. Conclusions. These results suggest that sunitinib effectively protects the liver from diabetes-induced damage through the inhibition of the Notch pathway

Sıçan hipertiroidi modelinde, ovaryum ve testis dokusunun histokimyasal ve moleküler olarak araştırılması

Amaç: Bu çalışmada, deneysel olarak hipertiroidi oluşturulan sıçanlarda; hipertiroidiye bağlı olarak testis ve ovaryum yapısındaki olası histopatolojik değişimler, hücre bağlantıları, kök hücre belirteçleri ve oksidatif stres açısından immunohistokimyasal, ışık mikroskobik olarak araştırılacaktır. Ayrıca Revers transkripsiyon- polimeraz zincir reaksiyonu (RT-PCR) yöntemi kullanılarak moleküler biyolojik olarak araştırılması amaçlanmıştır. Yöntem: Her biri 8 hayvandan oluşan 4 çalışma grubu oluşturuldu. Hipertiroidi grubundaki erkek ve dişi sıçanlara 10 gün boyunca intraperitonal 50μgr/100gr/gün olacak şekilde 3,3',5-Triiodo-L-thyronine enjekte edildi. 11. günde tüm gruplardaki hayvanlara anestezi uygulanmış, biyokimyasal değerlendirmeler için 5 cc kan alındıktan sonra da dekapite edilerek testis ve ovaryumları çıkarılmış ve histokimyasal, immünohistokimyasal ve RT-PCR uygulaması için uygun fiksatifler içine alınmıştır. Bulgular: H.E, Mallory Trikrom ve PAS ile yapılan boyamalarda testislerde, kontrol grubu ile karşılaştırıldığında hipertiroidi grubunda seminifer tübül ve interstisyumda yapısal değişiklikler gözlenmiştir. Ovaryumlarda ise hipertiroidi grubunda özellikle stromal dokuda ki yapısal değişiklikler dikkati çekmiştir. Testislerde, kök hücre belirteçlerinden, C- kit ve Thy- 1 ekspresyonu kontrol grubuna göre hipertiroidi grubunda belirgin düzeyde azalmış, Nanog ekspresyonuna ise heriki grupta da rastlanmamıştır. iNOS, Konneksin 43 ve Okludin ekspresyonları da kontrol grubuna göre hipertiroidi grubunda belirgin düzeyde azalmıştır. Ovaryumlarda ise, C- kit, Thy- 1, Konneksin 43 ve Okludin ekspresyonu kontrol grubuna göre hipertiroidi grubunda belirgin düzeyde azalmış, Nanog ve iNOS ekspresyonu ise hipertiroidi grubunda artmıştır. RT- PCR’ da, Konneksin 43, okludin, inhibin α, inhibin βA ve inhibin βB mRNA düzeylerinin testis ve ovaryum hipertiroidi gruplarında kontrol gruplarına göre artış gösterdiği saptanmıştır. Sonuç: Bulgularımız hipertiroidide literatürde üzerinde pek durulmayan organ parankim hasarı yerine destek mikro çevre bozunumunu göstermektedir. Parankimal yapı korunduğundan bizim modelimizdeki akut toksikozun geri dönüşlü olabileceği düşünülmektedir. Toksikozu sonlandırılmış sıçanlarda stromal değişikliklerin geri dönüşümlü olup olmadığı ileri çalışmalarla araştırılmalıdır

Suppression of exaggerated neuronal oscillations by oxytocin in a rat model of Parkinson's disease

WOS: 000337075300007PubMed ID: 23970035Increased oscillatory activity has been demonstrated in the basal ganglia of Parkinson's disease (PD) patients. The aim of the present study was to evaluate the effects of oxytocin (OT) on local field potentials (LFPs) in a rotenone-induced rat model of PD. Adult male Sprague-Dawley rats were unilaterally injected with rotenone (3 mu g/mu l in DMSO) into the left substantia nigra pars compacta whereas vehicle group was received only DMSO. PD-developed rats were then administered either OT (160 mu g/kg/day, i.p.) or saline for three weeks. Following treatment period, LFPs were recorded from the left striatum of freely moving rats and neuronal cell loss was evaluated by Nissl staining. We found significant increase in all frequency bands except delta in saline group when compared with vehicle (p <0.0005), while treatment of OT prevented these alterations in electroencephalography (EEG) recordings. Besides, histopathological evaluation of the striatal sections revealed a significant cell loss (p <0.005), whereas administration of rats with OT significantly lessened the neuronal death. These findings suggest that injury of dopaminergic neurons triggers exaggerated neuronal oscillations in the striatum and oxytocin may have some inhibitory effects on neuronal activity in PD

Effect of oxytocin administration on nerve recovery in the rat sciatic nerve damage model

WOS: 000362988300001PubMed ID: 26466786Background: Growth factors such as nerve growth factor (NGF) and insulin-like growth factor-1 (IGF-1) have been shown to play a role in the healing process of nerve injury. Recent researches have also shown that oxytocin administration activates these growth factors of importance for the healing of nerve tissue. The objective of the present study was to evaluate the effects of oxytocin on peripheral nerve regeneration in rats. Methods: Twenty-four male Sprague-Dawley rats were underwent transection damage model on the right sciatic nerve and defective damage model on the left sciatic nerve. The animals were assigned to one of two groups: control group or treatment group (received 80 mg/kg oxytocin intraperitoneally for 12 weeks). The sciatic nerve was examined, both functionally (on the basis of climbing platform test) and histologically (on the basis of axon count), 3, 6, 9, and 12 weeks after the injury. Also, stereomicroscopic and electrophysiological evaluations were carried out. Results: Significantly greater improvements in electrophysiological recordings and improved functional outcome measures were presented in the treatment group at 12-week follow-up. Stereomicroscopic examinations disclosed prominent increases in vascularization on proximal cut edges in the oxytocin group in comparison with the control group. Higher axon counts were also found in this group. Conclusion: Intraperitoneal oxytocin administration resulted in accelerated functional, histological, and electrophysiological recovery after different sciatic injury models in rats

Visible spectroscopy of 5CB/8CB liquid crystals

WOS: 000368610600004Electro-optical properties of nematic liquid crystals (LCs) have attracted a great deal of research interest and have resulted in a number of practical applications in many areas. In the present study, wavelength dependence of electro-optical properties of two different types of nematic LCs and their binary mixtures are investigated. LCs used in this study are 5CB and 8CB and their mixtures in different proportions. The optical transmittance of the structures has been studied by means of visible spectroscopy by measuring the transmitted light intensity as a function of the wavelength under various driving AC electric field values. Experiments were carried out at the wavelength interval 380-780 nm at a constant temperature of 25 degrees C in order to see the effect of the applied field alone

Omurga kist hidatiği ve albendezol, anteror ve posterior radikal eksizyon ve füzyon ile tedavisi: Olgu sunumu ve 11 yıllık takip sonuçları

Hydatid cyst is a zoonosis caused by the larval form of parasitic tapeworm Echinococcus granulosus. We present a case of vertebral hydatid cyst with paravertebral abscesses operated 11 years ago. A 32 year old woman presented multiple giant paravertebral abscesses at the level of T11-12 and L1 vertebrae and pathological fracture of L1 vertebra because of vertebral hydatid cyst. Posterior instrumentation and fusion followed by anterior L1 corpectomy and fusion were done. Patient was pain-free at eleven-year follow-up. There was no radiological evidence of relapse. Hydatid disease of the spine is rare, misdiagnosis and therefore inadequate treatment and recurrence is frequent. Maintaining the stability of the spine and achieving a fusion mass is important in the decision of surgical technique in vertebral type of hydatidosis.Hidatit kist Echinococcus granülozus’un larva formu ile oluşan bir zoonozdur. Bu çalışmada 11 yıl önce paravertebral apse ile birlikte vertebral hidatit kist nedeni ile ameliyat edilen olgu sunulmuştur. 32 yaşındaki kadın hastada T11-T12 ve L1 seviyelerinde yaygın paravertebral apse, L1 seviyesinde vertebral hidatit kiste bağlı patolojik kırık saptandı. Posterior enstrümantasyon ve füzyon, anterior L1 korpektomi ve füzyon uygulandı. Bir yıl sonraki kontrolde hastanın semptomları tamamen düzelmişti. Radyolojik tetkiklerde apse nüksü görülmedi. Oldukça nadir rastlanan vertebra kist hidatiği tanısı ve tedavisi zor bir enfestasyondur. Nüks ihtimali oldukça yüksektir. Omurganın stabilitesinin temin edilmesi ve füzyon kitlesinin elde edilmesi vertebral hidaditozun cerrahi tedavi kararında oldukça önemlidir

Exenatide promotes regeneration of injured rat sciatic nerve

WOS: 000400920000028PubMed ID: 28553346Damage to peripheral nerves results in partial or complete dysfunction. After peripheral nerve injuries, a full functional recovery usually cannot be achieved despite the standard surgical repairs. Neurotrophic factors and growth factors stimulate axonal growth and support the viability of nerve cells. The objective of this study is to investigate the neurotrophic effect of exenatide (glucagon like peptide-1 analog) in a rat sciatic nerve neurotmesis model. We injected 10 mg/d exenatide for 12 weeks in the experimental group (n = 12) and 0.1 mL/d saline for 12 weeks in the control group (n = 12). We evaluated nerve regeneration by conducting electrophysiological and motor functional tests. Histological changes were evaluated at weeks 1, 3, 6, and 9. Nerve regeneration was monitored using stereomicroscopy. The electrophysiological and motor functions in rats treated with exenatide were improved at 12 weeks after surgery. Histological examination revealed a significant increase in the number of axons in injured sciatic nerve following exenatide treatment confirmed by stereomicroscopy. In an experimentally induced neurotmesis model in rats, exenatide had a positive effect on nerve regeneration evidenced by electromyography, functional motor tests, histological and stereomicroscopic findings