Brain temperature in healthy and diseased conditions: A review on the special implications of MRS for monitoring brain temperature

Brain temperature determines not only an individual's cognitive functionality but also the prognosis and mortality rates of many brain diseases. More specifically, brain temperature not only changes in response to different physiological events like yawning and stretching, but also plays a significant pathophysiological role in a number of neurological and neuropsychiatric illnesses. Here, we have outlined the function of brain hyperthermia in both diseased and healthy states, focusing particularly on the amyloid beta aggregation in Alzheimer's disease

Chemogenetic inhibition of MCH neurons does not alter memory performance in mice

Memory storage in the brain is one of the most extensively studied subjects in neuroscience. However, due to the highly complex structure of the memory-related systems in the brain, the mystery remains unsolved. Consolidation is one of the most important parts of the memory process, and one that can be affected by numerous neurodegenerative diseases. Hypothalamic melanin-concentrating hormone (MCH) neuronal activity has been of particular interest to researchers in terms of the association between sleep, neurodegenerative diseases, and memory consolidation. We used Pmch-Cre animals to investigate the role of MCH neuronal activity in memory consolidation. In order to observe the differences in memory consolidation, we chemogenetically inhibited MCH neurons using the DREADD method and measured hippocampus-dependent memory performance with a novel object recognition test applicable to early memory impairment in Alzheimer's disease. Our results revealed no significant improvement or worsening with MCH inhibition, suggesting that the role of MCH should now be evaluated in a wider setting

Türkiye’de diş hekimlerinin bifosfonatlar konusundaki farkındalık ve bilgilerinin değerlendirilmesi

Aim: Bisphosphonates (BPs) are inorganic pyrophosphate analogs used for the treatment of various diseases. This study aimed to evaluate the knowledge and attitudes of general dental practitioners (GDP), specialist trainees (ST), and specialists (S) in Turkey toward medication-related osteonecrosis of the jaw (MRONJ) and to optimize future training programs in this field. Materials and Methods: A self-report questionnaire consisting of 7 questions about demographic data, knowledge about BPs, MRONJ and treatment modalities was prepared and send to the members of Turkish Dental Association via email. Results: A total of 209 participants were included in this survey. The mean age of the ST group was significantly lower than the mean ages of the GDP and S groups (P= 0.003, P= 0.038). GDP are less likely to think of BPs administration and radiotherapy treatment than S or ST upon observation of an exposed bone in the head-and-neck region (P=0.048, P=0.008). In comparison to the S and ST groups, the GDP group displayed less knowledge regarding the radiological and intraoral examination of patients undergoing BP therapy (P= 0.034). Conclusion: The increasing awareness of dentists about usage and side effects of BPs is important for preventing MRONJ. The GDP group displayed significantly less knowledge regarding the radiological and intraoral examinations of patients undergoing BP therapy. Greater efforts are required to increase education and knowledge of MRONJ and BPs among dental practitioners.Amaç: Bisfosfonatlar çeşitli hastalıkların tedavisinde kullanılan inorganik pirofosfat analoglarıdır. Bu çalışma uzman olmayan diş hekimlerinin, uzmanlık öğrencilerinin ve uzmanların ilaca bağlı gelişen çene osteonekrozuna yönelik bilgi ve tutumlarını değerlendirmenin yanında, gelecekteki eğitim programlarını optimize etmeyi amaçlamıştır. Materyal ve Metot: Çalışmaya 209 katılımcı dahil edilmiştir. Türk Dişhekimleri Birliği’nin desteğiyle bir anket hazırlanmış ve üyeler arasında e-posta ile paylaşılmıştır. Katılımcıların demografik bilgiler, ilaca bağlı çene osteonekrozları, bisfosfonatlar ve tedavi yaklaşımları ile ilgili 7 sorudan oluşan anketi yanıtlamaları istenmiştir. Bu anket sorularına hekimlerin verdiği cevaplar sayı ve yüzde ile tanımlanmıştır. Bulgular: Ankete katılan uzmanlık öğrencilerinin ortalama yaşı, uzman olmayan diş hekimleri ve uzmanlardan anlamlı olarak düşük bulunmuştur (P = 0.003, P = 0.038). Uzman olmayan diş hekimleri, baş-boyun bölgesinde gözlemlenen ekspoze kemiğin bisfosfonat tedavisi ya da radyoterapiye bağlı olabilme ihtimalini diğer gruplara göre daha az değerlendirmiştir (P=0.048, P=0.008). Uzman ve uzmanlık öğrencilerine kıyasla uzman olmayan diş hekimleri, bisfosfonat kullanan hastaların radyolojik ve ağız içi bulguları hakkında daha az bilgi sahibi olduğunu belirtmiştir (P = 0.034). Sonuç: Diş hekimlerinin bisfosfonatların kullanımı ve yan etkileri konusunda artan farkındalığı MRONJ’un önlenmesi için önemlidir. Diş hekimleri arasında MRONJ ve bisfosfonatlar ile ilgili bilincin artırılması için daha fazla çaba gösterilmesi ve hedef kitleye yönelik eğitim planları oluşturulması gerekmektedi

The effect of resveratrol on sphingosine-1 and oxidative/ nitrosative stress in an experimental heart ischemia reperfusion model

Objectives: Resveratrol (RSV) is a natural polyphenolic compound showing significant antioxidant effects. In this study, we aimed to investigate the effects of resveratrol on the sphingosine-1-phosphate (S1P) and oxidative stress biomarkers in hearth ischemia-reperfusion (I/R). Materials and Methods: The biochemical and histopathological effects of RSV on cardiac ischemia-reperfusion injury were investigated through ELISA- and light microscope. Results: We observed statistically significant differences between the treatment group and the control group in terms of malondialdehyde (MDA) level, catalase (CAT) and superoxide dismutase (SOD) activities (p<0.05). Histopathologically, we also observed decreased Polymorphonuclear Leucocyte (PMNL) infiltration, myocardial edema, miyositolysis in the treatment group compared to the I/R and sham groups. Conclusion: Resveratrol may play an important role in cardiac I/R injury through its anti-inflammatory and antioxidant effects which were biochemically and histopathologically confirmed in the present study

Conservative Approach to Unilateral Condylar Fracture in a Growing Patient: A 2.5-Year Follow Up

Condylar fractures in children are especially important because of the risk of a mandibular growth-center being affected in the condylar head, which can lead to growth retardation and facial asymmetry. The purpose of this article is to follow up the two and half year clinical and radiological evaluation of the conservative treatment of a 10 year-old patient, who had a unilateral green-stick type fracture. The patient presented with painful facial swelling localized over the left condylar region, limited mouth-opening and mandibular deviation to the left. Panoramic radiography and computed tomography confirmed the diagnosis of incomplete fracture on the left condyle with one side of the bone fractured and the other bent. Closed reduction was chosen to allow for initial fibrous union of the fracture segments and remodeling with a normal functional stimulus. A non-rigid mandibular splint was applied in order to remove the direct pressure on the fracture side of the mandible. Clinical and radiologic examination after 30 months revealed uneventful healing with reduction of the condylar head and remodeling of the condylar process following conservative treatment

Combined metabolic activators improve metabolic functions in the animal models of neurodegenerative diseases

Background: Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), are associated with metabolic abnormalities. Integrative analysis of human clinical data and animal studies have contributed to a better understanding of the molecular and cellular pathways involved in the progression of NDDs. Previously, we have reported that the combined metabolic activators (CMA), which include the precursors of nicotinamide adenine dinucleotide and glutathione can be utilized to alleviate metabolic disorders by activating mitochondrial metabolism. Methods: We first analysed the brain transcriptomics data from AD patients and controls using a brain-specific genome-scale metabolic model (GEM). Then, we investigated the effect of CMA administration in animal models of AD and PD. We evaluated pathological and immunohistochemical findings of brain and liver tissues. Moreover, PD rats were tested for locomotor activity and apomorphine-induced rotation. Findings: Analysis of transcriptomics data with GEM revealed that mitochondrial dysfunction is involved in the underlying molecular pathways of AD. In animal models of AD and PD, we showed significant damage in the high-fat diet groups' brain and liver tissues compared to the chow diet. The histological analyses revealed that hyperemia, degeneration and necrosis in neurons were improved by CMA administration in both AD and PD animal models. These findings were supported by immunohistochemical evidence of decreased immunoreactivity in neurons. In parallel to the improvement in the brain, we also observed dramatic metabolic improvement in the liver tissue. CMA administration also showed a beneficial effect on behavioural functions in PD rats. Interpretation: Overall, we showed that CMA administration significantly improved behavioural scores in parallel with the neurohistological outcomes in the AD and PD animal models and is a promising treatment for improving the metabolic parameters and brain functions in NDDs.PoLiMeR Innovative Training Network ; SNIC ; ScandiBio Therapeutics ; ScandiBio Therapeutics and Knut ; Knut och Alice Wallenbergs Stiftels

Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: A randomised, double-blinded, placebo-controlled phase-II trial

Background: Alzheimer’s disease (AD) is associated with metabolic abnormalities linked to critical elements of neurodegeneration. We recently administered combined metabolic activators (CMA) to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals. CMA promotes mitochondrial fatty acid uptake from the cytosol, facilitates fatty acid oxidation in the mitochondria, and alleviates oxidative stress. Methods: Here, we designed a randomised, double-blinded, placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients. One-dose CMA included 12.35 g L-serine (61.75%), 1 g nicotinamide riboside (5%), 2.55 g N-acetyl-L-cysteine (12.75%), and 3.73 g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84. The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms. The secondary aim of this study was to evaluate the safety and tolerability of CMA. A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients. Results: We showed a significant decrease of AD Assessment Scale-cognitive subscale (ADAS-Cog) score on day 84 vs day 0 (P = 0.00001, 29% improvement) in the CMA group. Moreover, there was a significant decline (P = 0.0073) in ADAS-Cog scores (improvement of cognitive functions) in the CMA compared to the placebo group in patients with higher ADAS-Cog scores. Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis. Moreover, the plasma levels of proteins and metabolites associated with NAD + and glutathione metabolism were significantly improved after CMA treatment. Conclusion: Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics, metabolomics, proteomics and imaging analysis. Trial registration ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131

The therapeutic role of minocycline in Parkinson's disease

Minocycline, a semisynthetic tetracycline-derived antibiotic, has been shown to exert anti-apoptotic, anti-inflammatory, and antioxidant effects. Furthermore, there is rapidly growing evidence suggesting that minocycline may have some neuroprotective activity in various experimental models such as cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, Parkinson's disease (PD), Huntington's disease, and multiple sclerosis. In this perspective review, we summarize the preclinical and clinical findings suggesting the neuroprotective role of minocycline in PD. © 2019 Cankaya S, Cankaya B, Kilic U, Kilic E, Yulug B. Published by Drugs in Context under Creative Commons License Deed CC BY NC ND 4.0 which allows anyone to copy, distribute, and transmit the article provided it is properly attributed in the manner specified below. No commercial use without permission