İskemik kalan ekstremitede reperfüzyon sonrası oluşan iskemi reperfüzyon hasarını azaltmak için deneysel sıçan modelinde feniramin maleat, çevresel hipotermi ve hiperterminin etkisinin araştırılması

Amaç: İskemik kalan dokunun reperfüzyonu ile birlikte ciddi doku hasarına neden olan iskemi reperfüzyon hasarı oluşur. Reperfüzyon akut inflamatuar kaskadı tetikleyerek hücre ölümüne, doku fonksiyonlarında bozulmaya ve nekroza neden olabilmektedir. Bu çalışmada deneysel olarak iskemi reperfüzyon hasarı oluşturulmuş ratlarda sistemik uygulanan feniramin maleatın ve çevresel sıcaklık değişimlerinin iskemi reperfüzyon hasarını azaltmaya yönelik etkilerinin araştırılması planlanmıştır. Elde edilen sonuçların daha önce yapılan hayvan çalışmalarında iskemi reperfüzyon hasarını azaltmadaki etkisi gösterilmiş olan ve sistemik olarak uygulanan N-asetil sistein (NAC) ile karşılaştırılması amaçlanmıştır. Gereç ve yöntem: Deney hayvanı olarak ağırlıkları 250-350 gr arasında olan 42 adet Sprague- Dawley rat kullanıldı. Ratlar eşit sayıda (n=7) olacak şekilde rastgele 6 gruba ayrıldı (sham, iskemi reperfüzyon (İR), İR+soğuk, İR+sıcak, İR+feniramin, İR+NAC). Sham grubu dışındaki gruplarda iskemi oluşturmak için genel anestezi altında, 3 saat boyunca, ratların sağ alt ekstremite femoral arterleri klemplendi ve kolateral dolaşımı engellemek için elastik turnike uygulandı. Reperfüzyon başlangıcında; İR+soğuk grubundaki ratların iskemik kalan ekstremitelerine periferik soğutma ve İR+sıcak grubundaki ratların iskemik ekstremitelerine periferik ısıtma işlemi 2 saat boyunca uygulandı. İR+ feniramin grubuna sistemik feniramin ve İR+NAC grubuna sistemik NAC reperfüzyon öncesi uygulandı. Yirmi dört saatlik reperfüzyon süresinin sonunda genel anestezi altında ratların sağ alt ekstremite gastrokinemius kasından histopatolojik ve biyokimyasal inceleme için doku örneklemesi yapıldı. Ayrıca birinci haftanın sonunda genel anestezi altında ratların sağ alt ekstremite tibialis anterior kasından histopatolojik inceleme için doku örnekleri alındı ve hayvanlar sakrifiye edildi. Yirmi dördüncü saatte alınan doku örneklerinde; oksidatif parametreler olan katalaz (KAT), myeloperoksidaz (MPO), süper oksit dismutaz (SOD), tiyobarbitürik asit ile reaksiyon veren maddeler (TBARS) ve poli adenozil difosfat riboz polimeraz (PARP) düzeyleri ölçüldü. Ayrıca hematoksilen eozin boyama ile inflamatuar hücreler değerlendirildi. Birinci haftanın sonunda alınan doku örnekleri hematoksilen eozin boyama ile kronik inflamasyon ve indüklenebilir nitrik oksit sentaz (iNOS) çalışılarak doku hasarı değerlendirildi. Bulgular: Kas dokusunda TBARS, MPO, KAT, SOD, PARP düzeyleri sham grubunda iskemi reperfüzyon yapılan diğer gruplara oranla anlamlı derecede düşük bulunurken (p<0.001). İR ve İR+sıcak grubunda diğer gruplara oranla anlamlı dercede yüksek bulundu (p<0.05). İR ve İR+sıcak grubunda akut ve kronik inflamasyon oranları ile iNOS boyanma şiddeti diğer gruplara oranla belirgin yüksek bulundu. İR+NAC ve İR+feniramin gruplarında TBARS, PARP, SOD, MPO, KAT düzeylerinin, iNOS boyanma şiddeti ve akut – kronik inflamasyon derecesinin anlamlı olarak düşük olduğu görüldü. Ayrıca İR+soğuk grubunda İR+NAC ve İR+feniramin grubuna oranla TBARS, MPO, KAT, SOD, PARP düzeyleri anlamlı derecede daha düşük saptandı. Sonuç: Kas dokusunda görülen İRH'ı ciddi hücre ve doku hasarına neden olmaktadır. Çalışmamızda NAC ve feniramin maleatın kas dokusunda oluşan İRH'nı önemli ölçüde azalttığını, aynı zamanda erken reperfüzyon döneminde uyguladığımız periferik soğutmanın İRH'nı NAC ve feniramin maleattan daha etkin bir şekilde azalttığını gördük. Periferik ısıtmanın ise İRH'na belirgin etkisinin olmadığını gözlemledik. Elde ettiğimiz bulgular yeni çalışmalarla desteklenerek İRH'nın önlenmesinde NAC, feniramin ve periferik soğutma gibi tedavi yöntemlerinin klinik uygulamalarda kullanımına ışık tutacaktır.Background: Ischemia-reperfusion (IR) injury is the tissue damage which caused by reperfusion of an ischemic tissue. Reperfusion triggers a cascade of acute inflammatory events which leading to cellular death and tissue dysfunction and necrosis. IR is commonly caused by tourniquet, amputation and replantation in orthopedic surgery. In this study, we aimed to investigate the protective effects of pheniramine maleate (Ph) and periferic hypothermia in rats which had been created experimentally ischemia reperfusion injury and compare the results with n-acetyl cysteine (NAC) known as an effective molecule for reducing IR. Materials and methods: Forty two Sprague-Dawley rats were seperated into 6 groups randomly (sham, IR, IR+local hypothermia, IR+local hyperthermia, IR+Ph, IR+NAC; n:7). To create ischemia we clamped the right femoral artery and applied tourniquet to the right hind limbs of rats during the 3 hours under general anesthesia. At the beginning of reperfusion, administered systemic Ph to the rats in the IR+Ph group and administered NAC to the rats in the IR+ NAC group. During two hours, the right hind limbs of rats in the IR+local hypothermia group were cooled by using cold water tank. And the right hind limbs of rats in the IR+local hyperthermia group heated similarly. At the end of the 24 hours reperfusion time, the right gastrocnemius muscles of all rats were sampled. In theese muscle samples; the oxidative parameters (Myleloperoxidase (MPO), supeoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS), poly adp ribose polymerase (PARP) levels) and inflammatory cells histopatologically were evaluated. The end of the one week reperfusion period, tibialis anterior muscles of all rats were sampled, then all of the rats were sacrificed. In these muscle samples, the iNOS staining and inflammatory cells histopathologically were evaluated. Results: In the IR group and IR+hyperthermia group, the levels of TBARS, PARP, SOD and CAT were found higher compared with those in the sham group. On the contrary, these oxidative parameters were found lower in IR+H, IR+Ph and IR+NAC groups compared with IR and IR+hyperthermia groups. Compared with the sham group; mononuclear inflammatory cells, tissue iNOS score and intensity staining in the IR, IR+hyperthermia groups were established increased. On the other hand, the histopathological parameters were found decreased in IR+H, IR+Ph, IR+NAC groups compared with the IR, IR+hyperthermia groups. Conclusion: In this study, we showed that NAC and Ph reduce the IR in muscle clearly, also hypothermia was more effective than NAC and Ph in reducing IR in muscle. Hyperthermia was found not effective in reducing or increasing IR. If our results are confirmed with new studies, NAC, Ph and hypothermia can be used for preventing or management of IR in clinical practises

Ilizarov bone transport and treatment of critical-sized tibial bone defects: a narrative review

Abstract Background Critical-sized bone defects of the tibia are complex injuries associated with significant problems that are difficult to treat, and they are associated with a significant burden of disease in clinical practice; however, the treatment of these cases has still been a challenge for orthopedic surgeons. The aim of this review was to evaluate the current available studies reporting on classical Ilizarov methods in the treatment of infected or noninfected critical-sized bone defects of the tibia, and to perform an analysis of treatment period and complications. Methods This is a narrative review based on a comprehensive literature search among the studies in Pubmed, Scopus and Web of Science articles. The studies included were written in the English language or translated to English and they were published between 2008 and 2018. They were appraised with narrative data synthesis. The primary outcome measures were the external fixation time (EFT), bone union rate, and bone and functional results. Secondary outcomes were complications including docking site problems and solutions. The heterogeneity of the data in the studies which were taken into consideration allowed a narrative analysis. Results Twenty-seven articles with 619 patients were included in this study. These included 6 prospective and 21 retrospective case series. Mean age was 36.1 (range 13–89) years. Of the cases, 88.8% were infected and the remaining 11.2% were noninfected. The external fixation time was 10.75 (range 2.5–23.2) months. The mean bone union rate was 90.2% (range 77–100)%. Radiographic outcome measures were reported in 20 studies. Functional outcome measures were reported in 18 studies. ASAMI (Association for the Study of the Method of Ilizarov) criteria are useful and give reproducible data on patient outcome measurements. Data collected from these studies showed excellent radiological outcomes in 303, good in 143, fair in 31, and poor in 25 patients. Functional outcomes were excellent in 200, good in 167, fair in 58, and poor in 19, where reported. The excellent and good rate in bone results and functional results were 88.8% and 82.6%, respectively. The poor rate in bone results and functional results were 5% and 4.5%. Mean complication rate per patient was 1.22 (range 3–60). The most common complication was pin tract infection (PTI). Its occurrence was 46.6%. Joint stiffness followed PTI with a 25% incidence. The rates of refracture, malunion, infectious recurrence, and amputation, were 4%, 8.4%, 4.58%, and 1%, respectively. Conclusions This narrative review shows that the patients with infected or noninfected critical-sized tibial bone defects treated by Ilizarov methods had a low rate of poor bone and functional results. Therefore, Ilizarov methods may be a good choice for the treatment of infected or noninfected tibial bone defects. The small number of cases in some studies, the absence of homogenity between studies and the fact that most data available are derived from retrospective studies are some of the difficulties encountered in the evaluation of evidence. Level of evidence V

Effect of pheniramine maleate on rat skeletal muscle ischemia-reperfusion injury

BACKGROUND: Skeletal muscle ischemia-reperfusion injury (IRI) is a common clinical problem encountered after tourniquet application or replantation. This study investigated the effect of pheniramine maleate (Ph), which is frequently used in clinical practice to reduce IRI, and compared its efficacy in IRI with N-acetylcysteine (NAC), a molecule that has been shown to be effective in IRI. METHODS: Twenty-eight male Sprague-Dawley rats were randomly divided into four groups (sham, ischemia-reperfusion [IR], IR+Ph, IR+NAC; n=7 rats per group). Ischemia was induced in the lower right extremities of rats for 3 h using a femoral artery clamp and an elastic tourniquet. Ph and NAC were administered intraperitoneally 15 min before ischemia was terminated. At 24 h after reperfusion, levels of thiobarbituric acid reactive substance (TBARS), catalase (CAT), myeloperoxidase (MPO), superoxide dismutase (SOD), polyadenosine diphosphate ribose polymerase (PARP), and neutrophil infiltration were evaluated. Inducible nitric oxide synthase (iNOS) density in muscle tissue was evaluated by immunohistochemical methods after 1 week. RESULTS: SOD, MPO, PARP, CAT, and TBARS levels in muscle tissue were significantly lower in the sham group compared with the other groups (p0.001). All parameters except TBARS were lower in the NAC and Ph groups than in the IR group (p0.001). Neutrophil infiltration in the muscle tissue samples from the IR group was significantly increased compared with the NAC and Ph groups (p0.05). iNOS staining was not observed in the sham and NAC groups. CONCLUSION: Ph is effective at reducing experimental rat skeletal muscle IRI.This study was funded by Ege University Scientific Research Project (Grant No. 2017TIP28).Ege University Scientific Research Project [2017TIP28

The cupric ion reducing antioxidant capacity and polyphenolic content of some herbal teas

The total antioxidant capacity of the aqueous extracts of some endemic herbs-prepared as infusions by steeping these herbs in hot water-was assayed with bis(neocuproine) copper(II) chloride, also known as the cupric ion reducing antioxidant capacity (CUPRAC) reagent, which was easily accessible, rapid, stable and responsive to both hydrophilic and lipophilic antioxidants. The highest antioxidant capacities of some herbal teas available in the Turkish market were observed for scarlet pimpernel (Anagallis arvensis), sweet basil (Ocimum basilicum), green tea (Camellia sinensis) and lemon balm (Melissa officinalis), in this order (1.63, 1.18, 1.07, and 0.99 mmol trolox equivalent (TR)/g, respectively). For infusions prepared from ready-to-use tea bags, the CUPRAC values were highest for Ceylon blended ordinary tea (4.41), green tea with lemon (1.61), English breakfast ordinary tea (1.26) and green tea (0.94), all of which were manufactured types of C. sinensis. Following the strongest antioxidant herbs with capacities close to or slightly exceeding 1.0 mmol TR/g, sage, thyme, coriander, coltsfoot, blackberry and immortelle (Helichrysum) exhibited capacities around 0.5 mmol TR/g. The correlation of the Folin total phenolic content of herbal teas with their CUPRAC and ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt) total antioxidant capacities gave linear curves with correlation coefficients of 0.966 and 0.936, respectively, showing that the CUPRAC assay results better correlated with total phenolic content of herbal teas. Absorbance versus concentration data at different dilutions and upon standard additions of model antioxidant compounds (trolox and quercetin) to herbal tea infusions showed that the absorbances (at 450 nm of the CUPRAC method) due to different antioxidant compounds in herbal tea infusions were additive; that is, the tested antioxidants did not chemically interact to cause apparent deviations from Beer's law