N-Methyl D-Aspartic Acid (NMDA) Receptors and Depression

The monoaminergic hypothesis of depression has provided the basis for extensive research into the pathophysiology of mood disorders and has been of great significance for the development of effective antidepressants. Current antidepressant treatments not only increase serotonin and/or noradrenaline bioavailability but also originate adaptive changes increasing synaptic plasticity. Novel approaches to depression and to antidepressant therapy are now focused on intracellular targets that regulate neuroplasticity and cell survival. Accumulating evidence indicates that there is an anatomical substrate for such a devastating neuropsychiatric disease as major depression. Loss of synaptic plasticity and hippocampal atrophy appear to be prominent features of this highly prevalent disorder. A combination of genetic susceptibility and environmental factors make hippocampal neurons more vulnerable to stress. Abundant experimental evidence indicates that stress causes neuronal damage in brain regions, notably in hippocampal subfields. Stress-induced activation of glutamatergic transmission may induce neuronal cell death through excessive stimulation of N-methyl-D-aspartic acid (NMDA) receptors. Recent studies mention that the increase of nitric oxide synthesis and inflammation in major depression may contribute to neurotoxicity through NMDA receptor. Both standard antidepressants and NMDA receptor antagonists are able to prevent stress-induced neuronal damage. NMDA antagonists are effective in widely used animal models of depression and some of them appear to be effective also in the few clinical trials performed to date. We are still far from understanding the complex cellular and molecular events involved in mood disorders. There appears to be an emerging role for glutamate neurotransmission in the search for the pathogenesis of major depression. Attenuation of NMDA receptor function mechanism appears to be a promising target in the search for a more effective antidepressant therapy

Gebelikte Tütün Dumanı Maruziyetinin Anne Sıçan Akciğer Dokusunda Meydana Getirdiği Değişiklikler Üzerine Alfa Lipoik Asitin Etkilerinin İncelenmesi

Amaç: Çalışmamızda gebelikte tütün dumanına maruz kalan anne sıçanların akciğer dokusunda meydana gelen değişiklikler üzerine alfa lipoik asitin etkilerinin deneysel sıçan modeli üzerinde araştırılması amaçlandı. Yöntemler: Çalışmada 28 adet dişi Sprague-Dawley cinsi sıçanlar kullanıldı. Gebe sıçanlar; Kontrol grubu, Tütün dumanı (TD) grubu, Tütün dumanı + Alfa lipoik asit (TD+ALA) grubu ve Alfa lipoik asit (ALA) grubu olmak üzere rastgele dört eşit gruba ayrıldı. TD ve TD+ALA grubundaki sıçanlar çiftleşmeden önce sekiz hafta ve gebelik süresince günde iki saat tütün dumanına maruz bırakıldı. TD+ALA ve ALA grubundaki sıçanlara ise çiftleşmeden önce sekiz hafta ve gebelik süresince gün aşırı oral gavaj yolu ile 20 mg/kg dozunda alfa lipoik asit verildi. Deneyin sonunda sıçanlar dekapite edilerek akciğer dokuları çıkarıldı ve histolojik, biyokimyasal ve immünohistokimyasal metotlar uygulandı. Bulgular: TD grubuna ait akciğer kesitlerinde inflamatuar hücre artışı, konjesyon, ödem, hemoraji gibi histopatolojik bulgular gözlendi. ALA uygulamasıyla bu histopatalojik bulgularda istatistiksel olarak anlamlı oranda düzelmeler izlendi. TD grubunda VEGF immünreaktivitesinin kontrol grubuna göre anlamlı artış gösterdiği, TD+ALA grubunda ise TD grubuna göre VEGF immünreaktivitesinin anlamlı derecede azaldığı belirlendi. TD grubunda MDA değerlerinin kontrole göre anlamlı derecede arttığı, TD+ALA grubunda ise TD grubuna göre anlamlı derecede azaldığı gözlendi. Sonuç: Tütün dumanının gebe sıçan akciğerinde yol açtığı oksidatif hasarın, alfa lipoik asit tedavisinin antioksidan etkileri ile kısmen engellendiği belirlendi

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Determination of ghrelin immunoreactivity in the rat stomach after fasting and refeeding

Ghrelin is a recently discovered hormone secreted by cells of the stomach. The aim of this study was to investigate fasting and refeeding induced alterations on ghrelin immunolabelling of cells of the stomach. Thirty-six adult mate Wistar rats were used in this study. Rats were divided into six groups. Group I: control group; Group II: rats fasted for 7 days; Group III: rats fed for 1 day after 7 days of fasting; Group IV: rats fed for 3 days after 7 days of fasting; Group V: rats fed for 5 days after 7 days of fasting; Group VI: rats fed for 7 days after 7 days of fasting. At the end of the experiment, rats were sacrificed and stomach tissues were processed for imunohistochemistry to localize ghrelin. Ghrelin-immunopositive cells were detected only in the mucosal lining of the stomach. After fasting for 7 days, the number of ghrelin-immunopositive cells increased significantly compared to the control rats. Following refeeding, the number of ghrelin-immunoreactive cells was reduced to a level comparable to the controls. Therefore, fasting and refeeding after fasting were observed to result in changes in ghrelin immunoreactivity in the cells of the stomach. We conclude that ghrelin is highly expressed in the stomach and that fasting increases the expression of ghrelin in the stomach, but this expression decreases after refeeding. Our results indicate that regutation of ghrelin is a process probably involved in the long-term control of nutritional states. (c) 2007 Elsevier GmbH. All rights reserved

The Effect of Oleuropein on Ghrelin Expression in Rat Testes with FructoseInduced Metabolic Syndrome

Bu çalışmada yüksek fruktoz diyeti ile deneysel olarak oluşturulan metabolik sendrom modelinin rat testis dokusuna etkileri ve ratların testis dokusundaki ghrelin ekspresyonunda oleuropein uygulanmasının meydana getireceği değişimlerin, biyokimyasal ve immünohistokimyasal yöntemlerle belirlenmesi amaçlandı. Sekiz haftalık 32 adet erkek Sprague-Dawley cinsi rat rastgele Kontrol, Metabolik sendrom, Oleuropein, Metabolik sendrom+Oleuropein olmak üzere 4 gruba ayrıldı. Metabolik sendrom oluşturmak amacıyla %20 fruktoz içeren içme suyu kullanıldı ve Oleuropein 10 mg/kg/gün oral olarak uygulandı. 60 günlük deney sonunda ratlar dekapite edilerek kan ve testis doku örnekleri alındı. Serum glukoz, insülin ve trigliserid düzeyleri ölçüldü. Testis dokularında streptavidin-biyotinperoksidaz yöntemi ile ghrelin immünreaktivitesi belirlendi. Ayrıca, testis dokularında malondialdehit (MDA) düzeyleri ve katalaz aktivitesi spektrofotometrik yöntemlerle ölçüldü. Fruktoz uygulamasının; serum trigliserid, insülin düzeyleri ve insülin direncinde anlamlı bir artış yaptığı saptandı. Yüksek fruktoz diyeti ile deneysel olarak metabolik sendrom oluşturulan ratların testis dokusunda ghrelin ekspresyonunun azaldığı, oleuropein uygulanmasının ise testis dokusunda azalmış ghrelin ekspresyonunu arttırdığı belirlendi. Metabolik sendrom grubunda testis dokusu MDA düzeylerinin arttığı ve katalaz aktivitesinin azaldığı belirlendi. Diğer taraftan metabolik sendrom+oleuropein grubunda, metabolik sendrom grubuna göre testis dokusunda MDA düzeylerinin azaldığı, katalaz aktivitesinin ise arttığı tespit edildi. Yüksek fruktoz diyeti ile oluşturulan metabolik sendrom modelinde, testis dokusunda oksidatif stresin arttığı saptandı. Metabolik sendromda bu doz ve sürede oleuropein uygulamasının, aşırı fruktoz tüketiminin neden olduğu olumsuz etkilere karşı testis dokusunda koruma sağladığı ve antioksidan bir rol oynadığı belirlendi.We aimed to investigate the effects of oleuropein administration on ghrelin expression in rat testes tissues with fructose-induced metabolic syndrome by immunohistochemical and biochemical methods. Thirty-two male adult (8 week aged) Sprague-Dawley rats were randomly divided into four groups (n=8); Control, Meabolic syndrome, Oleuropein, Metabolic syndrome plus Oleuropein. Metabolic syndrome was induced by fructose solution 20% in drinking water, and oleuropein was administered at the dose of 10 mg/kg daily by oral gavage. After the experimental period of 60 days, the rats were decapitated, testes tissues and blood samples were taken. Serum glucose, insulin and triglyceride levels were measured. The testes samples were immunehistochemically stained using avidin-biotin-peroxidase method for the determination of ghrelin immunoreactivity. Also testes tissue malondialdehyde (MDA) levels and catalase activity were determined spectrofotometrically. Fructose consumption significantly increased serum triglyceride, insulin levels and insulin resistance. Ghrelin immunoreactivity in rat testes tissues with fructose-induced metabolic syndrome was determined as low. Oleuropein administration increased testes ghrelin levels. In comparison with control group, MDA levels increased and CAT activities decreased in metabolic syndrome group. On the other hand MDA levels were diminished and Cat activities were elevated in fructose plus oleuropein group compared to the metabolic syndrome group. These results indicate that metabolic syndrome increases oxidative stress in testicular tissue. It can be suggested that at that the dose and time of oleuropein administration can play a role as an antioxidant and protect the testes from the effects of high fructose induced metabolic syndrome