Effects of tocilizumab and dexamethasone on the downregulation of proinflammatory cytokines and upregulation of antioxidants in the lungs in oleic acid-induced ARDS

Abstract Background: Acute respiratory distress syndrome (ARDS) is a life-threatening disease caused by the induction of infammatory cytokines and chemokines in the lungs. There is a dearth of drug applications that can be used to prevent cytokine storms in ARDS treatment. This study was designed to investigate the efects of tocilizumab and dexamethasone on oxidative stress, antioxidant parameters, and cytokine storms in acute lung injury caused by oleic acid in rats. Methods: Adult male rats were divided into fve groups: the CN (healthy rats, n=6), OA (oleic acid administration, n=6), OA+TCZ-2 (oleic acid and tocilizumab at 2 mg/kg, n=6), OA+TCZ-4 (oleic acid and tocilizumab at 4 mg/kg, n=6), and OA+DEX-10 (oleic acid and dexamethasone at 10 mg/kg, n=6) groups. All animals were euthanized after treatment for histopathological, immunohistochemical, biochemical, PCR, and SEM analyses. Results: Expressions of TNF-α, IL-1β, IL-6, and IL-8 cytokines in rats with acute lung injury induced by oleic acid were downregulated in the TCZ and DEX groups compared to the OA group (P<0.05). The MDA level in lung tissues was statistically lower in the OA+TCZ-4 group compared to the OA group. It was further determined that SOD, GSH, and CAT levels were decreased in the OA group and increased in the TCZ and DEX groups (P<0.05). Histopathological fndings such as thickening of the alveoli, hyperemia, and peribronchial cell infltration were found to be similar when lung tissues of the TCZ and DEX groups were compared to the control group. With SEM imaging of the lung tissues, it was found that the alveolar lining layer had become indistinct in the OA, OA+TCZ-2, and OA+TCZ-4 groups. Conclusions: In this model of acute lung injury caused by oleic acid, tocilizumab and dexamethasone were efective in preventing cytokine storms by downregulating the expression of proinfammatory cytokines including TNF-α, IL-1β, IL-6, and IL-8. Against the downregulation of antioxidant parameters such as SOD and GSH in the lung tissues caused by oleic acid, tocilizumab and dexamethasone upregulated them and showed protective efects against cell damage

Gerze Horoz ve Tavuklarında Larynx, Trachea ve Syrinx’in Anatomik Yapısının Belirlenmesi

Çalışma materyalini Karadeniz Bölgesinde yer alan Sinop İli’nin Gerze İlçe’sine ait yerel bir ırk olan ve bu yörede ötüşüyle ve görünümüyle tanınan Gerze horozu ve tavuğu oluşurdu. Larynx, trachea ve syrinx’in incelendiği bu çalışmada 7 erkek ve 7 dişi olmak üzere toplam 14 hayvan kullanıldı. Larynx’in kıkırdaklarını tek olan cartilago cricoidea, cartilago procricoidea ve çift olan cartilago arytenoidea oluşturdu. Erkeklerdeki glottis genişliğinin (3,54±0,37) dişilerdekinden (1,35±0,42) fazla olduğu dikkat çekti. Dış larynx kasları m. cricohyoideus, m. cleidotrachealis ve m. tracheolateralis, iç larynx kasları ise m. dilator glottidis ve m. consrictor glottidis olarak belirlendi. Trachea 112-117 adet tam daire şeklindeki kıkırdak halkadan oluştu. Gerze horoz ve tavuklarında syrinx tracheobronchial tipti. Syrinx’in oluşumuna katılan cartt. tracheosyringeales’in 12-13 adet kıkırdak halkadan oluştuğu gözlendi. Bunlardan cranial’deki 8-9 adet kıkırdak halka tympanum’u oluşturdu. Diğerlerinin ise daha ince ve yassı olduğu ve membrana tympaniformis lateralis’in içinde gömülü olarak bulunduğu saptandı. Yandan kama biçiminde görünen pessulus, dorsal ve ventral’den ise ikizkenar üçgen şeklinde idi. Sonuç olarak, diğer kuş türleri ile farklılıkları bulunan Gerze horoz ve tavuğunun larynx, trachea ve syrinx’inin genel olarak evcil kanatlılarla benzerlik gösterdiği belirlendi

The evaluation of right ventricle dyssynchrony by speckle tracking echocardiography in systemic sclerosis patients

Purpose Systemic sclerosis (SSc) is associated with right ventricle (RV) remodeling and dysfunction. The primary aim of this study was to evaluate RV dyssynchrony (RV-Dys) in SSc patients using two-dimensional speckle tracking echocardiography (2D-STE). Methods Fifty-five SSc patients with functional class I-II and 45 healthy controls were consecutively included and underwent 2D-STE. RV-Dys was defined as the standard deviation of time to peak strain of mid and basal segments of RV free wall and interventricular septum. SSc group was further classified according to the presence of pulmonary arterial hypertension (PAH). Patients with tricuspid regurgitant velocity >2.8 m/s with additional echocardiographic PAH signs were defined as SSc PAH (+). Results SSc patients had lower RV longitudinal strain (RV-LS) (-17.6 +/- 4.6% vs. -20.8 +/- 2.8%, p < 0.001) and greater RV-Dys (49.9 +/- 25.4 ms vs 24.3 +/- 11.8 ms, p = 0.006) than controls despite no significant difference in conventional echocardiographic variables regarding RV function. Although SSc PAH(+) patients had lower RV-LS and higher RV-Dys than SSc PAH(-) patients, the differences were not statistically significant. The only independent predictor of RV-Dys was RV-LS (beta:-0.324 [-3.89- -0.45]; p = 0.014). Conclusion SSc patients had not only reduced RV-LS but also impaired RV synchronicity even as conventional echocardiographic variables were preserved

Mycobacterial RNA isolation optimized for non-coding RNA: high fidelity isolation of 5S rRNA from Mycobacterium bovis BCG reveals novel post-transcriptional processing and a complete spectrum of modified ribonucleosides

A major challenge in the study of mycobacterial RNA biology is the lack of a comprehensive RNA isolation method that overcomes the unusual cell wall to faithfully yield the full spectrum of non-coding RNA (ncRNA) species. Here, we describe a simple and robust procedure optimized for the isolation of total ncRNA, including 5S, 16S and 23S ribosomal RNA (rRNA) and tRNA, from mycobacteria, using Mycobacterium bovis BCG to illustrate the method. Based on a combination of mechanical disruption and liquid and solid-phase technologies, the method produces all major species of ncRNA in high yield and with high integrity, enabling direct chemical and sequence analysis of the ncRNA species. The reproducibility of the method with BCG was evident in bioanalyzer electrophoretic analysis of isolated RNA, which revealed quantitatively significant differences in the ncRNA profiles of exponentially growing and non-replicating hypoxic bacilli. The method also overcame an historical inconsistency in 5S rRNA isolation, with direct sequencing revealing a novel post-transcriptional processing of 5S rRNA to its functional form and with chemical analysis revealing seven post-transcriptional ribonucleoside modifications in the 5S rRNA. This optimized RNA isolation procedure thus provides a means to more rigorously explore the biology of ncRNA species in mycobacteria.Singapore-MIT Alliance for Research and TechnologyNational Institute of Environmental Health Sciences (ES017010)National Institute of Environmental Health Sciences (ES002109)Singapore-MIT Alliance (Graduate Fellowship)Singapore. National Research Foundatio