Novel SNARE Complex Polymorphisms Associated with Multiple Sclerosis: Signs of Synaptopathy in Multiple Sclerosis

Background: It is well known that axonal degeneration plays a role in disability in patients with multiple sclerosis, and synaptopathy has recently become an important issue.Aims: To investigate the possible roles of selected synaptic and presynaptic membrane protein genetic polymorphisms (VAMP2, SNAP-25, synaptotagmin, and syntaxin 1A) in patients with multiple sclerosis.Study Design: Case-control study.Methods: A total of 123 patients with multiple sclerosis and 192 healthy controls were included. The functional polymorphisms of specific SNARE complex proteins (VAMP2, synaptotagmin XI, syntaxin 1A, and SNAP-25) were analyzed by polymerase chain reaction.Results: Significant differences were detected in the genotype and allele distribution of 26-bp Ins/Del polymorphisms of VAMP2 between patients with multiple sclerosis and control subjects; Del/Del genotype and Del allele of VAMP2 were more frequent in patients with multiple sclerosis (p=0.011 and p=0.004, respectively). Similarly, Ddel polymorphism of SNAP-25 gene C/C genotype (p=0.059), syntaxin 1A T/C and C/C genotypes (p=0.005), and synaptotagmin XI gene C allele (p=0.001) were observed more frequently in patients with multiple sclerosis. CC, syntaxin rs1569061 1A gene for 33-bp promoter region TC haplotypes, and synaptotagmin XI gene were found to be associated with an increased risk for multiple sclerosis (p=0.012). Similarly, GC haplotype for rs3746544 of SNAP-25 gene and rs1051312 of SNAP-25 gene were associated with an increased risk for multiple sclerosis (p=0.022).Conclusion: Genetic polymorphisms of SNARE complex proteins, which have critical roles in synaptic structure and communication, may play a role in the development of multiple sclerosis

Hipoksik iskemik ensefalopati oluiturulan rat modelinde indometazinin nöronal apopitoz üzerine etkisi

TEZ7794Tez (Yandal Uzmanlık) -- Çukurova Üniversitesi, Adana, 2010.Kaynakça (s. 53-61) var.ix, 62 s. : res. (bzs. rnk.) ; 29 cm.Amaç: Siklooksijenaz yolağı ve prostaglandinler hipoksik-iskemik beyin hasarı patogenezinde ve gecikmiş beyin hasarı mekanizmasında önemli rol oynar. Bu çalışmada hipoksik iskemik rat modelinde farklı dozlardaki nonselektif siklooksijenaz inhibitörü olan indometazinin nöronal apopitoz üzerine etkisi araştırıldı. Gereç ve Yöntem: Levine-Rice metoduna göre hipoksik iskemi oluşturulan yedi günlük ratlar beş gruba ayrıldı. Grup I (n: 15) ratlara serum fizyolojik verildi, arter ligasyonu ve hipoksi yapılmadı. Grup II (n: 15) ratlara hipoksik-iskemiden sonra serum fizyolojik verildi. Grup III (n: 15) ratlara hiposik-iskemiden önce tek doz 2 mg/kg indometazin verildi. Grup IV (n: 15) ratlara hipoksik-iskemiden sonra 12 saat arayla üç doz 2 mg/kg indometazin verildi. Grup V (n: 15) ratlara hipoksik-iskemiden sonra 12 saat arayla üç doz 4 mg/kg indometazin verildi. Ratlar hipoksik-iskemiden 72 saat sonra dekapite edildi ve beyin hemisfer dokuları TUNEL yöntemi ile değerlendirildi. Bulgular: Hipoksik-iskemi öncesi ve sonrası verilen indometazin tedavisi hipoksik-iskemi sonrası serum fizyolojik verilen grup ile karşılaştırıldığında rat beynindeki apopitotik hücre sayısını önemli ölçüde azalttı (p<0,001). Sonuç: Bu sonuçlara göre indometazin tedavileri hipoksik iskemik beyin hasarı tedavisinde iyi bir seçenek olabilir.Purpose: Cyclooxygenase pathway and prostaglandins plays an important role in the pathogenesis and delayed mechanisms of hypoxic-ischemic brain injury. The aim of this study was to investigate the effect of different doses of indomethacin, a nonselective cyclooxygenase inhibitor, on neuronal apoptosis in rats with hypoxic-ischemic brain injury. Material and Methods: Seven-day-old rat pups with the Rice model of hypoxic-ischemic cerebral injury were randomly divided into five groups. Group I (n: 15) pups were given physiologic saline, but neither ligation nor hypoxia were performed. Group II (n: 15) pups were treated with physiologic saline after hypoxic-ischemia. Group III (n: 15) pups were treated with indomethacin at a dose of 2 mg/kg per before hypoxic ischemia. Group IV (n: 15) pups were treated with three doses of indomethacin at a dose of 2 mg/kg every 12 h after hypoxic-ischemia. Group V (n: 15) pups were treated with three doses of indomethacin, at a dose of 4 mg/kg every 12 h after hypoxic ischemia. After 72 hours, the rats were decapitated and each brain hemispheres tissues were evaluated by using the TUNEL staining method. Results: Indomethacin treatment either before or after hypoxia, results in a significant reduction in the numbers of apoptotic cells in rat brains when it is compared with group treated with physiologic saline after hypoxic-ischemia (p<0,001). Conclusion: These results demonstrated that indomethacin administration either before or after hypoxic-ischemia reduce neuronal apoptosis, and we propose that indomethacin may be a good option for the therapy of hypoxic-ischemic brain injury.Bu çalışma Ç.Ü. Tıp Fakültesi Araştırma Fonu tarafından desteklenmiştir. Proje No: TF2006LTF32

Comparison Of Less Invasive Surfactant Delivery Techniques In Respiratory Distress Syndrome

Background: This study was conducted to evaluate and compare the effectiveness of newly developed minimal invasive methods for surfactant administration (LISA by using Magill forceps, INSURE) Methods: The research was conducted on 15 patients between 685-2100 gr weight, requiring surfactant administration. Poractant alpha, dose 200 mg/kg, was administered to patients with spontaneous breathing on continuous positive airway pressure support. LISA was used to administer surfactant to 7 of 15 patients, whereas 8 of them had surfactant administered using the INSURE method. Results: The data regarding the delivery method, birth weight, gender, prenatal history, usage of steroids, APGAR scores and other data about the patients until hospital discharge were recorded. Desaturation and bradycardia for 3-4 minutes were observed in 71% (5/7) of LISA and 87.5% (7/8) of INSURE cases. Bradycardia was observed in 4 of 8 patients from the INSURE group and positive ventilation was needed. From the INSURE group, 3 patients died; one of 15 had ROP and this patient was from the INSURE group. No difference was found among the groups regarding required duration of O2 and days of hospital stay (p&lt;0.05). The thin catheter group had significantly fewer median days on mechanical ventilation and lower rate of mortality (p&lt;0.05). Conclusions: When there is no need for mechanical ventilation, intubation for surfactant administration was determined not to be necessary in the present study. LISA was observed to be the best method for surfactant administration among the methods without intubation

Paket Vücut Sendromuna Bağlı Kokain İntoksikasyonu Sonucu Ölüm Olgu Sunumu

Yasadışı ilaç ve uyuşturucu maddeleri vücutlarının içinde paket halinde saklamak suretiyle gümrüklerden ve kontrol noktalarından kaçıran kişilere vücut paketçisi denmektedir. Yabancı uyruklu 24 yaşında erkek olgu, fenalaşması üzerine getirildiği hastanede konvülsiyonlar geçirerek ölmüştür. Dış muayenesinde herhangi bir özellik yoktur. İç organ incelemelerinde; organlarda yaygın ödem ve konjesyon görülmüştür. Midesinde ve bağırsaklarında iki adet kokain paketi mevcut olduğu tespit edilmiştir. Olgu; vücudundaki paketlerden birinin patlaması sonucunda akut kokain intoksikasyonu sonucu öldüğüne karar verilmiş bir paket vücuttur. Olgu; şüpheli ölümlerde “Paket Vücut Sendromu”na dikkat çekmek ve konunun tartışılması amacıyla sunulmuştur. Anahtar kelimeler: Kokain, paket vücut sendromu, şüpheli ölüm, otopsi, adli tı

İzmir ili Ödemiş ilçesinde kırmızı et tüketim davranışlarının belirlenmesi üzerine bir araştırma

The aim of this research is to determine effective factors on beef, mutton and goat meat consumption, and the meat consumption patterns of inhabitants of ;Ouml;demiş, İzmir based on education and income levels. To that end, a questionnaire was conducted over 497 inhabitants between October and December in 2008. So it was found that 87.1% of the participants consumed meat whereas 12.9% did not. The preferred meat types were as follows; beef (66.7%), mutton (16.7%), goat meat (8.6%), and all types (8.0%). Meat was bought as ground meat (50.6%), portion (38.5%) or with bone (10.9%). Consumption habits of red meat were the grilled (19.3%), boiled (16.8%), in oven (8.6%), with a mix of vegetable(s) (15.4%) and roasted (8.2%). 46.3% of the consumers claimed to pay attention to its freshness and the other variances of importance were lean 30.9%, price,7.6% and these all 15.2%. As to the processing animals under hygienic conditions, 62.3% of the respondents agree, while 9.6% disagree and 27.2% absent.Bu araştırmanın amacı, İzmir ili Ödemiş ilçesinde yaşayanların sığır, koyun ve keçi eti tüketimlerine etkili faktörler ile eğitim ve gelir düzeylerine göre kırmızı et tüketim davranışlarının belirlenmesidir. Bu amaçla, 2008 yılının Ekim-Aralık ayları arasında 497 tüketiciye anket uygulanmıştır. Ankete katılanların %87.1’inin kırmızı et tükettiği, %12.9’unun ise tüketmediği saptanmıştır. Kırmızı et tüketenler, etin elde edildiği hayvan türüne göre tercihlerini sırasıyla; sığır (%66.7), koyun (%16.7), keçi (%8.6) ve fark etmez (%8.0) olarak belirtmişlerdir. Kırmızı eti tüketicilerin %50.6’sı kıyma, %38.5’i parça et, %10.9’u ise kemikli et olarak almayı tercih etmektedir. Kırmızı etin pişirme yöntemi olarak, görüşülen tüketicilerin % 19.3’ü ızgara, %16.8’i haşlama, %8.6’sı fırında, % 8.2’si yağda kızartarak ve %15.4’ü sebze yemeklerinin içinde tükettiklerini ifade etmişlerdir. Kırmızı eti satın alırken tüketicilerin, %46.3’ü tazeliğine, %30.9’u yağsız oluşuna ve %15.2’si tüm özelliklerine, % 7.6’sı ise fiyatına dikkat ettiklerini belirtmişlerdir. Ankete katılanların %62.3’ü hayvanların hijyenik koşullarda kesildiğini düşünürken, %9.6’sı aynı düşüncede olmadıklarını, %27.2’i ise bir fikri olmadığını belirtmiştir

Indomethacin Prevents Neuronal Apoptosis in Newborn Rats with Hypoxic-Ischemic Brain Injury

WOS: 000291330700015Objective: Cyclooxygenase pathway and prostaglandins play an important role in the pathogenesis and delayed mechanisms of hypoxic-ischemic brain injury. The aim of this study was to investigate the effect of different doses of indomethacin, a nonselective cyclooxygenase inhibitor, on neuronal apoptosis in rats with hypoxic-ischemic brain injury. Material and Methods: Seven-day-old rat pups with the Rice model of hypoxic-ischemic cerebral injury were randomly divided into five groups. Group 1 (n=15) pups were given physiologic saline, neither ligation nor hypoxia were performed. Group 2 (n=15) pups were treated with physiologic saline after hypoxic-ischemia. Group 3 (n=15) pups were treated with indomethacin at a dose of 2 mg/kg before hypoxic ischemia. Group 4 (n=15) pups were treated with three doses of indomethacin at a dose of 2 mg/kg every 12 h after hypoxic-ischemia. Group 5 (n=15) pups were treated with three doses of indomethacin, at a dose of 4mg/kg every 12 h after hypoxic ischemia. After 72 hours, the rats were decapitated and brain hemispheres were evaluated by the TUNEL (Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling) staining method. Results: Indomethacin treatment, either before or after hypoxia, resulted in a significant reduction in the numbers of apoptotic cells in the rat brain when compared to those who were treated with physiologic saline after hypoxic-ischemia (P<0.001). Conclusion: Our results demonstrated that indomethacin administration, either before or after hypoxic-ischemia, reduces neuronal apoptosis; and we propose that indomethacin may be a potential choice of treatment for hypoxic-ischemic brain injury.Cukurova University Research FoundationCukurova UniversityThis study was supported by the Cukurova University Research Foundation

Allopurinol’s effect on caspase-3 and caspase-8 activity in hypoxic-ischemic newborn rats

Amaç: Hipoksi-iskemi sonrası reperfüzyon-reoksijenasyon döneminde küçük damar endotel hücrelerinde serbest radikallerin üretimine neden olan siklooksijenaz ve ksantin oksidazın aktive olduğu iki önemli yol tetiklenir. Ksantin oksidaz inhibitörü olan allopürinolün hipoksik iskemik ansefalopatide nöroprotektif olabileceği gösterilmiştir. Kaspaz-3 ve kaspaz-8 nöronal apopitozda anahtar bir role sahiptir. Bu çalışmada yenidoğan sıçanlara hipoksi-iskemi sonrası değişik dozlarda uygulana allopürinolün beyin dokusunda apopitozun öncül proteinleri olan kaspaz-3 ve kaspaz- 8 aktivitesine etkisi araştırıldı. Gereç ve Yöntem: Çalışmada her gruba yedi günlük 10 sıçan alındı. Etik Kurul onayı (TIBDAM-25) alınan sıçanların sol karotis arteri bağlanıp 2,5 saat hipokside bırakıldı. Kontrol (S) ve hipoksi iskemi (H-İ) gruplarına ilaveten, bir gruba (AL48) 30 dak ve 12 saat sonra, bir gruba da (AL72) 30 dak ve 12 saate ilaveten 24 saat sonra 24 mg/kg dozda allopurinol periton içine uygulandı. Son ilaç uygulanmasından 24 saat sonra sıçanlar kafaları kesilerek beyin dokusunda kaspaz-3 ve kaspaz 8 aktivitelerine bakıldı. Bulgular: Tüm grupların kendi sağ ve sol beyin kaspaz-3 ve kaspaz-8 aktiviteleri arasında fark yoktu (p>0,05). H-İ, AL48 ve AL72 gruplarının her iki beyin küresindeki kaspaz-3 ve kaspaz-8 düzeyleri kontrol grubuna göre belirgin yüksekti (hepsi için p=0,0001). Ancak AL48 grubu ile H-İ grubu arasındaki kaspaz düzeyleri farklılık göstermez iken (p>0,05), AL72 grubunda kaspaz düzeyleri hem Hİ hem de AL48 grubuna göre daha düşüktü (sırası ile p=0,0001, p=0,001). Çıkarımlar: Toplam 72 mg/kg allopürinol verilen hipoksik iskemik yenidoğan sıçanların beyin dokularında kaspaz-3 ve kaspaz-8 düzeylerinin azalması, bu dozdaki allopürinolün hipoksik iskemik hasarda nöronal apopitozu azaltarak etkili olabileceğini düşündürmektedir. (Türk Ped Arfl 2013; 48: 48-52)Aim: During reperfusion period of hypoxia-ischemia, cyclooxygenase and xanthine oxidase pathways are induced. A xanthine oxidase inhibitor, allopurinol has been shown to be neuroprotective in hypoxic- ischemic encephalopathy. Caspase-8 and caspase-3 have a key role in neuronal apoptosis. We aimed to test repeated doses of allopurinol’s effect on caspase-3 and caspase-8 activities in newborn rats with hypoxic-ischemic encephalopathy. Material and Method: Seven days old newborn rats were taken and there were 10 rats in each group. After Ethical Committee was approved (TIBDAM-25), rats were subjected to left carotid artery ligation and hypoxia (8% oxygen and 92% nitrogen) for two and half hours. Hypoxic ischemic rats treated with 24 mg/kg allopurinol 30 minutes and 12 hours (AL48 group), and 30 minutes, 12 and 24 hours (AL72 group) after hypoxic- ischemic insult. Twenty four hours after last dose, rats were decapitated. The others groups were sham and saline- treated hypoxic- ischemic (H-I) group. Caspase- 3 and caspase- 8 activities were measured in both hemispheres. Results: There was no difference in caspase-3 and caspase-8 activities between right and left brain hemispheres in each group (p>0.05). Caspase-3 and caspase-8 activities were significantly lower in sham group when compared to H-I group, AL48 and AL72 groups (all ofp=0.0001). Even though there were no difference activities of caspase- 3 and caspase- 8 between H-I group and AL48 group (p>0.05), activities of caspase- 3 and caspase- 8 in AL72 group were significantly lower than H-I group and AL48 group (respectively p= 0.0001, p=0.001). Conclusions: Decreased activities of caspase- 3 and caspase- 8 in AL72 group may suggest that totally dosage of 72 mg/kg allopurinol may be effective for reducing neuronal apoptosis in newborn rats with hypoxic- ischemic insult. (Turk Arch Ped 2013; 48: 48-52