Several decades of research have sought to characterize tumor cell metabolism in the hope that tumor-specific activities can be exploited to treat cancer. Having originated from Warburg's seminal observation of aerobic glycolysis in tumor cells, most of this attention has focused on glucose metabolism. However, since the 1950s cancer biologists have also recognized the importance of glutamine (Q) as a tumor nutrient. Glutamine contributes to essentially every core metabolic task of proliferating tumor cells: it participates in bioenergetics, supports cell defenses against oxidative stress and complements glucose metabolism in the production of macromolecules. The interest in glutamine metabolism has been heightened further by the recent findings that c-myc controls glutamine uptake and degradation, and that glutamine itself exerts influence over a number of signaling pathways that contribute to tumor growth. These observations are stimulating a renewed effort to understand the regulation of glutamine metabolism in tumors and to develop strategies to target glutamine metabolism in cancer. In this study we review the protean roles of glutamine in cancer, both in the direct support of tumor growth and in mediating some of the complex effects on whole-body metabolism that are characteristic of tumor progression.

Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer.

https://www.journal-of-hepatology.eu/article/S0168-8278(16)30199-4/pdf

Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis

Objectives: The objectives of this systematic review were to assess the survival rate of implants placed in sites with transalveolar sinus floor elevation. Material and Methods: An electronic search was conducted to identify prospective and retrospective cohort studies on transalveolar sinus floor elevation, with a mean follow-up time of at least 1 year after functional loading. Failure and complication rates were analyzed using random-effects Poisson regression models to obtain summary estimates/ year proportions. Results: The search provided 849 titles. Full-text analysis was performed for 176 articles, resulting in 19 studies that met the inclusion criteria. Meta-analysis of these studies indicated an estimated annual failure rate of 2.48% (95% confidence interval (95% CI): 1.37‐4.49%) translating to an estimated survival rate of 92.8% (95% CI): 87.4‐96.0%) for implants placed in transalveolarly augmented sinuses, after 3 years in function. Furthermore, subject-based analysis revealed an estimated annual failure of 3.71% (95% CI: 1.21‐11.38%), translating to 10.5% (95% CI: 3.6‐28.9%) of the subjects experiencing implant loss over 3 years. Conclusion: Survival rates of implants placed in transalveolar sinus floor augmentation sites are comparable to those in non-augmented sites. This technique is predictable with a low incidence of complications during and post-operatively.

A systematic review of the success of sinus floor elevation and survival of implants inserted in combination with sinus floor elevation

Carnosine (β-alanyl-l-histidine) was discovered in 1900 as an abundant non-protein nitrogen-containing compound of meat. The dipeptide is not only found in skeletal muscle, but also in other excitable tissues. Most animals, except humans, also possess a methylated variant of carnosine, either anserine or ophidine/balenine, collectively called the histidine-containing dipeptides. This review aims to decipher the physiological roles of carnosine, based on its biochemical properties. The latter include pH-buffering, metal-ion chelation, and antioxidant capacity as well as the capacity to protect against formation of advanced glycation and lipoxidation end-products. For these reasons, the therapeutic potential of carnosine supplementation has been tested in numerous diseases in which ischemic or oxidative stress are involved. For several pathologies, such as diabetes and its complications, ocular disease, aging, and neurological disorders, promising preclinical and clinical results have been obtained. Also the pathophysiological relevance of serum carnosinase, the enzyme actively degrading carnosine into l-histidine and β-alanine, is discussed. The carnosine system has evolved as a pluripotent solution to a number of homeostatic challenges. l-Histidine, and more specifically its imidazole moiety, appears to be the prime bioactive component, whereas β-alanine is mainly regulating the synthesis of the dipeptide. This paper summarizes a century of scientific exploration on the (patho)physiological role of carnosine and related compounds. However, far more experiments in the fields of physiology and related disciplines (biology, pharmacology, genetics, molecular biology, etc.) are required to gain a full understanding of the function and applications of this intriguing molecule.

Physiology and Pathophysiology of Carnosine

The cytokine network in inflammatory bowel disease (IBD) is a complex, dynamic system that plays an important role in regulating mucosal innate and adaptive immune responses. While several studies have been done to evaluate immunomodulatory profiles in murine IBD, they have been limited to a relatively small number of cytokines that do not take into account its dependency of the interplay of multiple factors, and therefore the diagnostic potential of their cytokine profiles have been inconclusive. Herein we demonstrate a novel approach of comprehensive serum multiplex cytokine profiling to describe the modulation of 16 Th1, Th2, Th17 cytokines and chemokines in both acute and chronic murine models of DSS and TNBS-induced colitis. Distinctive disease-specific cytokine profiles were identified with significant correlations to disease activity and duration of disease. TNBS colitis exhibits heightened Th1-Th17 response (increased IL-12 and IL-17) as the disease becomes chronic. In contrast, DSS colitis switches from a Th1-Th17-mediated acute inflammation (increased TNFα, IL6, IL-17 and KC) to a predominant Th2-mediated inflammatory response (increase in IL-4 and IL-10 and concomitant decrease in TNFα, IL6, IL-17 and KC) in the chronic state. Profiles of multiple cytokines seen systemically were also validated locally in colonic mucosa. Moreover, advanced multivariate analyses identified discriminatory cytokine profiles that can be sufficiently used to distinguish unaffected controls from diseases, and one disease type from another. IL-6 and IL-12 stratified gender-associated disease activity in chronic colitis. Our studies provide insight into disease immunopathogenesis and illustrate the significant potential of utilizing multiplex cytokine profiles and bioinformatics as diagnostic tools in IBD.

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Distinct cytokine patterns identified from multiplex profiles of murine DSS and TNBS-induced colitis.

The effect of selenium and/or vitamin E treatments on radiation-induced intestinal injury in rats.

We retrieved and analysed the records of 527 odontogenic tumours from a total of 62,565 cases in the department of tumour pathology in the Institute of Oncology, University of Istanbul, from 1971 to 2003. Of these 527 tumours, 521 were benign and 6 were malignant. The most common lesions were ameloblastomas (n=133) followed by odontomas (n=109), odontogenic myxomas (n=83) and others. There were more female patients (n=278, 53%) than male, and nearly half the patients (n=253, 48%) were between the ages of 10 and 29 years. The posterior mandible was the commonest site (n=184, 35%), followed by the premolar area of the mandible (n=98, 19%), and the anterior maxilla (n=84, 16%).

Odontogenic tumours in Istanbul: 527 cases.

Background: The reconstruction of edentulous patients with adequate bone volume and density by using dental implants has become a viable treatment option with high predictability. However, initial stabilization is difficult to achieve in the posterior maxillary regions where cortical bone is thin or absent due to severly resorbed alveolar ridges. Maxillary sinus lift procedures applied with various grafting materials enable clinicians to place implant-supported prostheses even in cases with increased pneumatization of the maxillary sinus. Methods: The purpose of this study was to evaluate histologically and clinically different grafting materials used in maxillary sinus floor augmentation. Deproteinized bovine bone granules (DBBG), demineralized freeze-dried bone powder (DFBP), and porous hydroxyapatite (PHA) were used as grafting materials. A total of 19 implants in 8 patients were placed into grafted sites. In 3 patients, a 2-stage approach was used wherein implants were inserted after a 6-month healing...

Histological and clinical evaluation of 3 different grafting materials for sinus lifting procedure based on 8 cases.

Clinical and histopathological investigation of odontomas: review of the literature and presentation of 160 cases.

Background/aims Hepatocyte apoptosis is an important and invasive predictor of liver injury and fibrosis in non-alcoholic fatty liver disease (NAFLD). Increased gamma-glutamyltranspeptidase (GGT) level is frequently observed in NAFLD. Hepatocyte growth factor (HGF) stimulates fibrogenesis and is correlated with GGT. The study aimed to determine whether GGT can distinguish NAFLD patients at high risk. Methodology Fifty biopsy-proven NAFLD patients (M/F: 24/26) were divided as the normal GGT group (n = 25) and the high GGT group (n = 25) (each patients' GGT > two fold of upper-limit of normal). Liver histology was graded according to Brunt et al. TNF-sRp55, caspase-3 and 8, NFkappaB and Bcl-2 were measured by immunohistochemical methods. For statistical analysis, Student's t test, chi-square test, multivariate regression analysis and the area under receiver operating characteristic (ROC) curve were used. Results The high GGT group had significantly higher NFkappaB, caspase-3 and 8, and Bcl-2 levels (54.52 +/- 26.02, p = 0.002; 55.95 +/- 27.18, p = 0.002; 47.85 +/- 28.04, p = 0.001; 11.19 +/- 12.33, p = 0.016, respectively). Serum TNF-sRp55 levels of both groups were similar (2922.93 +/- 307.26, and 2885 +/- 194.47; p = 0.78). Differences in reference to histological steatosis grade and inflammation were not significant. However, fibrosis stage was higher in the high GGT group (p = 0.048). Conclusion Multinominal logistic regression analysis showed that increased GGT level was a risk factor for advanced fibrosis in NAFLD (OR: 1.0, CI: 0.98-1.01; p =0.032). Using serum GGT levels the area under the ROC curve for the prediction of advanced fibrosis was 0.74 (95% CI: 0.54-0.94). The serum GGT cut-off value for the prediction of advanced fibrosis was 96.5 U/L; with 83% sensitivity and 69% specificity.

Vakur Olgaç

Papers

The effect of selenium and/or vitamin E treatments on radiation-induced intestinal injury in rats.

Odontogenic tumours in Istanbul: 527 cases.

Histological and clinical evaluation of 3 different grafting materials for sinus lifting procedure based on 8 cases.

Clinical and histopathological investigation of odontomas: review of the literature and presentation of 160 cases.

Serum gamma-glutamyltranspeptidase distinguishes non-alcoholic fatty liver disease at high risk.