Obesity and Anesthesia Management

The prevalence of obesity is rapidly increasing throughout the world. Correspondingly, anesthetic procedures in obese patients are also increasing due to both treatment of obesity and other surgical problems of obese patients. Anesthesia-related complications are also seen in obese patients than in normal-weighted population. The importance of anesthetic applications in obese patients originates from physiological and pharmacokinetic alterations. Inhalation of these patients via mask or intubation during general anesthesia may be difficult or even impossible. Determination of extubation time after awakening from anesthesia is also a critical decision. Sleep apnea syndrome and postoperative atelectasis are more common in obese patients than in normal-weighted population. Another vital complication that should be emphasized is thromboembolism, whose incidence and severity may be decreased by pharmacological and functional preventive modalities. This patient population has elevated risk of perioperative mortality and morbidity. Prior to any elective surgical procedure, an obese patient should be thoroughly evaluated to check medical conditions that may increase perioperative mortality risk. Since anesthesiologists will gradually encounter more obese patients, they need a better comprehending of the difficulties of obesity during anesthetic procedures and taking more preventive measures for their patients to avoid complications, or rendering them less traumatic, if any

Effects of oleanolic acid administration on renal NF-κB/IL-18/IL-6 and YKL-40/KIM-1 pathways in experimental diabetic rats

Objective(s): Neuropathy, retinopathy, and nephropathy, known as the triopathy of diabetes, are the consequences of microvascular complications of diabetes. The present study aimed to investigate the potential protective effects of oleanolic acid (OA) administration against diabetic nephropathy considering biochemical and histopathological parameters.Materials and Methods: The rats with fasting blood glucose levels of 200 mg/dl and above were considered diabetic after induction of diabetes via injecting STZ. The other half of the rats were not injected with STZ (healthy rats). Both healthy and diabetic rats were then divided randomly into two subgroups to be administered with either OA (5 mg/kg) with 1 ml tap water by oral gavage or 1 ml tap water in the same route for 21 days. Serum urea-N, Ca, P, and Mg as well as renal tissue MDA, SOD, NF-κB, IL-6, IL-18, AMPK, YKL-40, and KIM-1 levels were measured.Results: OA administration partially decreased levels of serum urea-N and P, as well as levels of renal tissue MDA and inflammation markers (NF-κB, IL-6, IL-18, YKL-40, and KIM-1) in the diabetic rats. It also partially increased serum Ca and renal tissue AMPK levels in diabetic rats. These positive effects were also seen in renal tissue histopathology.Conclusion: OA treatment partially alleviated renal damage inflammatory and oxidative profiles in diabetic rats

Simulation of activational grinding for rhombic sulfur particles in a disintegrator (pinned disc mill)

Based on the theoretical studies, complete picture of a mechanical processing of sulfur in the disintegrator is given. Kinematic and dynamic characteristics of elastic and inelastic collisions of particles of processed rhombic sulfur with rows of disintegrator fingers are calculated. Based on the analysis of the obtained dependency of the rotation frequency of the rotors offers, advices on selecting optimal conditions for activation milling of α-sulfur in the disintegrator are given. These results can be partially used in the processing of sulfur and in other types of shock grinding devices, in particular, jet mills

Discovery of therapeutic agents targeting PKLR for NAFLD using drug repositioning

Background: Non-alcoholic fatty liver disease (NAFLD) encompasses a wide spectrum of liver pathologies. However, no medical treatment has been approved for the treatment of NAFLD. In our previous study, we found that PKLR could be a potential target for treatment of NALFD. Here, we investigated the effect of PKLR in in vivo model and performed drug repositioning to identify a drug candidate for treatment of NAFLD. Methods: Tissue samples from liver, muscle, white adipose and heart were obtained from control and PKLR knockout mice fed with chow and high sucrose diets. Lipidomics as well as transcriptomics analyses were conducted using these tissue samples. In addition, a computational drug repositioning analysis was performed and drug candidates were identified. The drug candidates were both tested in in vitro and in vivo models to evaluate their toxicity and efficacy. Findings: The Pklr KO reversed the increased hepatic triglyceride level in mice fed with high sucrose diet and partly recovered the transcriptomic changes in the liver as well as in other three tissues. Both liver and white adipose tissues exhibited dysregulated circadian transcriptomic profiles, and these dysregulations were reversed by hepatic knockout of Pklr. In addition, 10 small molecule drug candidates were identified as potential inhibitor of PKLR using our drug repositioning pipeline, and two of them significantly inhibited both the PKLR expression and triglyceride level in in vitro model. Finally, the two selected small molecule drugs were evaluated in in vivo rat models and we found that these drugs attenuate the hepatic steatosis without side effect on other tissues. Interpretation: In conclusion, our study provided biological insights about the critical role of PKLR in NAFLD progression and proposed a treatment strategy for NAFLD patients, which has been validated in preclinical studies. Funding: ScandiEdge Therapeutics and Knut and Alice Wallenberg Foundation

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\ua0combined 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\ua0g L-serine (61.75%), 1\ua0g nicotinamide riboside (5%), 2.55\ua0g\ua0N-acetyl-L-cysteine (12.75%), and 3.73\ua0g L-carnitine tartrate (18.65%). AD patients received one dose of CMA or placebo daily during the first 28\ua0days 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\ua0CMA 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\ua0ClinicalTrials.gov NCT04044131 Registered 17 July 2019, https://clinicaltrials.gov/ct2/show/NCT04044131

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

Küçük sanayi işletmelerinde finansman kaynakları içinde kredilerin yeri ve bir uygulama

TEZ1226Tez (Yüksek Lisans) -- Çukurova Üniversitesi, Adana, 1990.Kaynakça (s. 89-92) var.92 [3] s. ; 30 cm.

Mandibula korpus kırıklarında farklı tedavi yöntemlerinin karşılaştırılması

Tez (Uzmanlık Tezi) -- Kırıkkale Üniversitesiref. no : 10197285119867

Comparision of different treatment modalities in mandibular body fractures

YÖK Tez ID: 509660Çocuklarda mandibula kırıklarının görülme sıklığı yetişkinlere göre oldukça düşük olsa da maksillofasiyal bölgede en çok gözlenen kırıklardır ve tedavilerinde birçok farklı yöntem tanımlanmıştır. Ultrason destekli fiksasyon sistemleri çocuklarda kraniyel ve orta yüz kırıklarının fiksasyonunda başarılı bir şekilde kullanılmaktadır ancak mandibula kırıklarının tedavisinde kullanımı sınırlıdır. Tez çalışmamızda 28 adet immatür, 6-8 haftalık erkek Yeni Zellanda tavşanı kullanıldı ve denekler her bir grupta 7 hayvan olacak şekilde 4 farklı gruba ayrıldı. İzole mandibula korpus kırıkları oluşturuldu. Tüm kırık hatları repoze edildikten sonra titanyum vidalar veya ultrason destekli pin ve rezorbe olabilen mesh veya plak kullanılarak fikse edildi. Operasyondan 2 ay sonra kırık hatlarının iyileşmesini değerlendirmek için tavşanlar sakrifiye edildi. Elde edilen örnekler histolojik ve histomorfometrik olarak değerlendirildi. Değerler istatistiksel olarak analiz edildi. Tüm örneklerde yeni kemik oluşumu gözlendi. Postoperatif olarak titanyum vidalar ile fikse edilen gruplarda, ultrason destekli pinler ile fikse edilen gruplara göre daha yüksek miktarda yeni kemik oluşumu gözlendi. Tüm gruplar arasında en yüksek yeni kemik oluşum miktarı titanyum vida/plak grubunda ölçüldü. Ancak yeni kemik oluşum miktarı açısından 4 grup arasında da istatistiksel olarak anlamlı bir fark bulunamadı. Bu tez çalışması çocuklarda mandibula korpus kırıklarının tedavisinde ultrason destekli pin/mesh uygulamasının alternatif bir tedavi yöntemi olabileceğini göstermektedir.Pediatric mandibular fractures are uncommon and have been treated by a wide variety of fixation methods. Ultrasound-aided fixation systems have been used for the pediatric cranial and facial bones but they have limited indication on treatment of mandibular fractures. Twenty eight immature, 6-8 weeks old male New Zealand rabbits were used, four groups, seven animals in each group. Isolated mandibular body fractures were created. All fractures were repositioned and fixed with resorbable plates or meshes and ultrasound aided pins or titanium screws. All of the animals were sacrificed two months after surgery. Histological and histomorphometric examinations were performed on the harvested hemi mandibles. The data were statistically analyzed. New bone formation has detected on all samples. The Titanium screw groups showed higher scores than ultrasound aided pin groups regarding the new bone area postoperatively. Plate + Titanium screw group showed highest new bone formation. However, there were no significant differences between amounts of new bone formation among 4 groups. This study suggested that ultrasound aided meshes + sonic pin application could be an alternative treatment method for pediatric mandibular body fractures