Medicine

Objective: The timing of administration of pharmacologic agents is crucial in traumatic stress since they can either potentiate the original fear memory or may cause fear extinction depending on the phase of fear conditioning. Brain noradrenergic system has a role in fear conditioning. Data regarding the role of prazosin in traumatic stress are controversial. Methods: In this study, we examined the effects of prazosin and the noradrenergic system in fear conditioning in a predator stress rat model. We evaluated the direct or indirect effects of stress and prazosin on noradrenaline (NA), gamma-aminobuytyric acid (GABA), glutamate, glycine levels and choline esterase activity in the amygdaloid complex, the dorsal hippocampus, the prefrontal cortex and the rostral pons. Results: Our results demonstrated that prazosin might alleviate defensive behaviors and traumatic stress symptoms when given during the traumatic cue presentation in the stressed rats. However prazosin administration resulted in higher anxiety levels in non stressed rats when the neutral cue was presented. Conclusion: Prazosin should be used in PTSD with caution because prazosin might exacerbate anxiety in non-traumatized subjects. However prazosin might as well alleviate stress responses very effectively. Stress induced changes included increased NA and GABA levels in the amygdaloid complex in our study, attributing noradrenaline a possible inhibitory role on fear acquisition. Acetylcholine also has a role in memory modulation in the brain. We also demonstrated increased choline esterase acitivity. Cholinergic modulation might be another target for indirect prazosin action which needs to be further studied.

Background The current coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan, China, and has rapidly become a global challenge, creating major challenges to health systems in almost every country in the world it has turned into a pandemic. COVID-19 poses a risky clinical situation that can range from mild illness to severe respiratory failure, requiring admission to intensive care. Main body It is known that SARS-CoV-2 infection causes a cytokine storm in some critically ill patients. However, more and more evidence showed that there is a dramatic increase in cytokine levels in patients diagnosed with COVID-19. Midkine (MK) is involved in various physiological and pathological processes, which some of them are desired and beneficial such as controlling tissue repair and antimicrobial effects, but some others are harmful such as promoting inflammation, carcinogenesis, and chemoresistance. Also, MK is e...

Background The aim of the study was to evaluate the presence and effects of hematological and biological parameters in the diagnosis of the disease by performing blood tests on COVID-19 patients admitted to the intensive care unit (ICU). Results Biochemical parameters from the blood samples of 279 patients who were confirmed to have COVID-19 and met the criteria for admission to the ICU were compared between discharged and deceased patients. Multiple logistic regression analysis was performed in terms of mortality and probability of being discharged. The predictive value of serum C-reactive protein (CRP), procalcitonin (PCT), lymphocyte, neutrophil, leucocyte, and platelet (PLT) levels was evaluated by measuring the area under the receiver operating characteristic curve (AUROC). Comparisons made according to deceased and survival patients results revealed that while no statistically significant difference was observed between test groups lymphocyte and platelet-lymphocyte ratio valu...

Objective: We tested the hypothesis that the spiking activity of hippocampal neurons may contain information about the reward-predictive value of task-relevant signals during reinforcement learning (1,2). Materials and Methods: Rats performed a well-learned (85% correct) conditional spatial goal selection task on a T-maze where two different removable start boxes (cue) at the stem of the maze signaled which maze arm contained food reward. The task had cue (15 s), choice (3 s), reward (3 s) and inter-trial interval (ITI, 40 s) periods. Correct choices received food reward. The sessions lasted 60-80 trials, where the reward magnitude was constant in blocks of 20 trials but otherwise varied randomly between three levels. The activity of CA1 neurons was recorded using a chronic headstage. The firing rate of putative excitatory neurons was fit in each task period as a function of task-relevant covariates using Generalized Linear Models. Results: Neurons with well-defined place fields in ...

The outbreak of coronavirus disease 2019 (COVID-19) in December 2019, reportedly caused by novel coronavirus known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), thereby the concerns to combat the pandemic has risen worldwide. The pandemic began in Wuhan, China and soon spread at an unprecedented rate that cost hundreds of thousands of lives due to high transmissibility and pathogenicity. The disease severity has been the subject of various factors including host immune response, gender, genetic factors, preexisting medical conditons, and the virus’s evolutionary pattern. Although the causes of evolution are yet to be known, the research studies demonstrate the changes in the structural genome of the virus, particulary the genes that encode the receptor-binding proteins (RBD). The purpose of this review is to provide the current literature and findings on virology of SARS-CV-2 structure and genetic factors of the host and the virus that may shed lights to future st...

The coronavirus disease-2019 (COVID-19) pandemic has caused important health, economic, social, and cultural problems worldwide. Recent findings demonstrate an excessive cytokine release during the disease development, especially in the seriously life-threatening form of COVID-19. Among other chemokines and cytokines that are released in high amounts at the infection site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), midkine (MK), which is an important pro-inflammatory growth factor/ cytokine, can be also overexpressed and contribute to the pathophysiological process in patients infected with SARS-CoV-2. Serum was collected from 87 intensive care unit (ICU) patients that are COVID-19 positive and 50 healthy volunteers in the control group with a negative PCR test and without disease symptoms. Circulating MK concentration was measured by enzyme-linked immunosorbent assay (ELISA) using a commercial human MK kit. COVID-19 patients had a significantly higher serum MK ...

Aim: To our knowledge; this is the first study that compared the efficacy and safety of aripiprazole 1-month and paliperidone 1month and paliperidone 3-month long-acting forms preparations as well as plasma drug levels during the maintenance treatment of schizophrenia in the real world. Method: In our study, subjects were evaluated every month for four months with relevant psychiatric measures and plasma drug levels. Follow-up days were determined as days 0, 30, 60, and 90. Plasma drug levels of the treatments were analyzed by using LC/MS-MS. Results: No superiority was observed between the groups regarding PANSS positive and general psychopathology (p>0.05). It was observed that PANSS negative and total scores were statistically lower in the aripiprazole once-monthly group than in the paliperidone 3-month preparations (p<0.05). We observed that Quality of Life Scale interpersonal relations scores, the aripiprazole 1-month group exhibited higher scores than both of the paliperidone groups. Aripiprazole 1-month group scored higher than the paliperidone 1-month group in the intrapsychic foundations subscale (p<0.05). No significant difference was observed between extrapyramidal adverse effect, akathisia, and insight levels among the three groups (p>0.05). Aripiprazole 1-month group scored significantly lower than both paliperidone groups in the Arizona Sexual Experiences Scale (p<0.001). Aripiprazole metabolite was negatively correlated with depressive symptoms in the Calgary Depression Assessment Scale in Schizophrenia (p<0.05) and the Barnes Akathisia Rating Scale (p<0.05). Conclusion: Aripiprazole once-monthly showed superiority in efficacy aspects to PP3M but not PP1M and similar safety with both paliperidone formulations.

Çalışmamızın amacı Sağlık Bakanlığı Hastane Medulla Sistemi kullanılarak polifarmasiye maruz kalan 65 yaş ve üstü hastalarda, ilaç-ilaç etkileşimlerinin belirlenip, ciddi etkileşimleri olan hastalarda klinik önlem alınması için farkındalık yaratmaktır. Çalışmamız Gebze 1 nolu Aile Sağlığı Merkezi’nden hizmet almakta olan 65 yaş üstü, Hasta Yönetim Platformu veri tabanında yer alan 188 hasta üzerinde yapılmıştır. Lexicomb® ilaç etkileşimi modülü ile hastaların kronik olarak kullandıkları ilaçlar listelenerek etkileşim düzeyleri değerlendirilmiştir. Bununla birlikte yaşlılarda uygunsuz ilaç kullanımı değerlendirilmesinde kullanılan kriterler üzerinde de durulmuştur. Çalışma sonuçlarımıza göre, 167 hastada toplamda 529 potansiyel ilaç-ilaç etkileşimi görüldü. Bu etkileşimlerin 52’sinde (%9,8) bilinen bir etkileşim saptanmadı ve risk kategorisi A olarak tespit edildi. B, C, D ve X risk kategorilerinde ilaç-ilaç etkileşimi sayıları sırasıyla, 74 (%13,9), 363(%68,6), 33 (%6,2) ve 7 (%1,3)...

Koronavirüs 19 (COVID-19) pandemisinin başlangıcından itibaren, bulaşmayı azaltacak ve ciddi vakalrın oluşumunu engelleyecek ilaç ve aşı müdahalelerinin yapılması farmakovijilans konusunu gündeme getirmiştir. Aşı uygulamasına geçiş süreci, farmakovijilans farkındalığını şekillendirme ve mevcut advers etki geri bildirim sistemini geliştirme fırsatı yaratmıştır. Çalışmamızın amacı aşılama hizmetlerinde kilit rol oynayan aile hekimlerinin; COVID-19 aşılama programlarında, aşı farmakovijilanşı ve aşı sonrası istenmeyen etki sinyalizasyon sisteminin uygulanması hakkındaki bilgi, tutum ve davranışlarının değerlendirilmesidir. Gereç ve Yöntem: Kesitsel ve tanımlayıcı tipte yapılan bu anket çalışmasında, Gebze ilçesinde görevli toplam 109 aile hekiminden, anket çalışmasına gönüllü 57 aile hekimine farmakovijilans konusunda bilgi, tutum ve uygulamalarını değerlendirmek için aşı sonrası istenmeyen etkiler konusunda 20 soruluk anket uygulanmıştır. Bulgular: Ocak 2021 yılında sağlık çalışanlarının aşılanmaya başlanmasıyla birlikte geçen altı aylık süreçte, 57 hekime yönlendirilen anket sonuçlarından 37 tanesi değerlendirildi. Anket sonuçlarına göre, aile hekimleri, aşı farmakovijilansı konusunda bilgi düzeylerini yeterli görmemekte ve konu hakkında eğitim ihtiyacı içindedirler. COVID-19 aşıları uygulamaları hakkında, aşı sonrası istenmeyen etkiler (%68,4) ve aşının uzun dönem istenmeyen etkileri (%63,2) aile hekimlerini en çok tedirgin eden konulardır. Ankete katılan aile hekimlerinin %23,7'si ASİE olabileceğini düşündükleri bir durumla karşılaşmalarına rağmen bildirim yapmamışlardır. Sonuç: Çalışmanın sonucunda, aşı farmakovijilansı konusunda aile hekimlerinin bilgi, tutum ve davranışlarının yetersiz olduğu ve COVID-19 gibi acil kullanım onayı alan aşıların uygulanmasının aile hekimlerinde tedirginlik yarattığı görüldü. Hekimlerin diğer farmakovilans konularında olduğu gibi aşı farmakovijilansı sinyalizasyon sistemi konusunda da ileri eğitime ihtiyacı olduğu ortaya konmuştur. Anahtar Sözcükler: COVID-19; farmakovijilans; aşı sonrası istenmeyen etki.

The current coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged in Wuhan, China and has rapidly become global challenges, creating major challenges to health systems in almost every country in the world it has turned into a pandemic. COVID-19 poses a risky clinical situation that can range from mild illness to severe respiratory failure requiring admission to intensive care. It is known to cause cytokine storm in some critically ill patients. However, more and more evidence showed that there is a dramatic increase in cytokine levels in patients diagnosed with COVID-19. Midkine (MK) is involved in various physiological and pathological processes, which some of them are desired and beneficial such as controlling tissue repair and antimicrobial effects, but some others are harmful such as promoting inflammation, carcinogenesis and chemo-resistance. Also, MK is expressed in inflammatory cells and released by endothelial cells under hypoxic conditions. Considering all this information, there are strong data that MK, an important cytokine known to increase in inflammatory diseases, may overexpressed in patients who are positive for COVID-19. The overexpression of MK reveals a picture leading to fibrosis in the lung damage. Therefore, questions arise about how the concentration of MK changes in CoVID-19 patients and can we use it as an inflammation biomarker or in the treatment protocol in the future.

The coronavirus disease-2019 (COVID-19) pandemic has caused important health, economic, social, and cultural problems worldwide. Recent ndings demonstrate an excessive cytokine release during the disease development, especially in the seriously life-threatening form of COVID-19. Among other chemokines and cytokines that are released in high amounts at the infection site of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), midkine (MK), which is an important pro-in ammatory growth factor/ cytokine, can be also overexpressed and contribute to the pathophysiological process in patients infected with SARS-CoV-2. Serum was collected from 87 intensive care unit (ICU) patients that are COVID-19 positive and 50 healthy volunteers in the control group with a negative PCR test and without disease symptoms. Circulating MK concentration was measured by enzyme-linked immunosorbent assay (ELISA) using a commercial human MK kit. COVID-19 patients had a signi cantly higher serum MK concentration compared to non-COVID-19 control subjects (1892.8 ± 1615.8 pg/ml versus 680.7 ± 907.6 pg/ml, respectively; P < 0.001). The cutoff MK concentration was 716.7 pg/ml, with the sensitivity and speci city of 75.9 % and 76.0 %, respectively. The area under the receiver operating characteristic (ROC) curve (AUC ROC) of MK was = .827. Our ndings showed that circulating MK levels are signi cantly increased in SARS-CoV-2 infected patients. We suggest that MK is involved in the pathogenesis of COVID-19 and may be a part of hypercytokinaemia. Therefore, MK may serve as a supporting in ammatory marker in the diagnosis of COVID-19 and by blocking MK actions or its targets may attenuate the in ammatory process and the severity of the disease.