The Markers Of Bone Metabolism And System Inflammation In Patients With Osteoarthritis Depending On Body Mass, The Influence Of Symptomatic Slow Acting Drugs

Aim. To assess the levels of markers of the bone synthesis and system inflammation in patients with osteoarthritis (OA) in combination with obesity and their dynamic under the influence of basic treatment.Materials and methods. The research included 40 women with OA, 46–78 years old (mean age – 59,8±1,5 years). Duration of the disease varied from 3 to 36 years (mean duration – 10,0±1,1 years). Mean body mass index (BMI) among patients was 30,6±0,7 [22,3; 39,5]kg/m2, according to which patients were divided in 3 groups: patients with OA without obesity (n=17), patients with OA with 1 degree of obesity (n=14), patients with OA with 2 degree of obesity (n=9). The level of osteochondral metabolism was assessed using quantitative measuring of the levels of procollagen IC-terminal propeptide (РІСР), (Cloud-CloneCorp. “procollagen IC-Terminal Propeptide”, USA) and osteocalcin (Roche Diagnostics «N-MID Osteocalcin», Switzerland) on analyzer «ELECSYS 2010» by the method of immune-enzyme analysis; the level of the system inflammation was assessed by the level of C-reactive protein (CRP) by the method of immunoturbidimetry. The clinical efficacy was assessed by the dynamics of intensity levels of pain syndromes at physical load and at rest by the visual-analogue scale (VAS). The measuring of РІСР, osteocalcin and CRP levels and also the assessment of clinical efficacy as to the decrease of pain syndrome were carried out twice – at the beginning and at the end of observation. The period of observation is 2 months.Results. The presence of direct correlation between РІСР and BMI (r=0,62; р=0,008) among patients with OA in combination with the normal body weight was established at the research, whereas among patients with OA in combination with obesity the analogous correlation was demonstrated between SRP and BMI (r=0,43; р=0,04) on the background of correlation of PICP and OC levels (r=0,46; р=0,03).Obesity in patients with OA was associated with the reliably higher levels of pain at both rest and physical load from the side of knee joints, with maximal intensity of the pain syndrome among patients with OA and 1 degree of obesity.Statistical analysis did not reveal the reliable dependence of РІСР and OC in patients with OA from the initial CRP level on the background of tendency to the higher РІСР level and lower OC level among patients with initially increased CRP level comparing with ones with normal CRP level. The therapy with basic preparations at OA during 2 months among patients with OA with increased CRP level led to the reliable decrease of РІСР level (р=0,0076) and the tendency to increase of OC level (р˃0,05), without the reliably significant difference between the initial and final РІСР and OC levels among patients with OA and normal CRP level.At the end of observation period the maximal analgesic effect was demonstrated as to the articulate pain at rest from the side of knee joints (р˂0,001) among patients with OA, who received diacerein, with clinically comparable effect from the side of other aticulate zones (р˂0,05), that was associated with reliable decrease of CRP level (р=0,013).Discussion. The received results testify that the control of the system inflammation level at OA is a target not only relative to the decrease of pain syndrome but also conditions the stable state of subchondral bone (SCB), providing the compensation of processes of destruction and synthesis in bone tissue. The significance of procollagen IC-terminal propeptide (РІСР) and osteocalcin (OC) as the markers of bone synthesis that are able to reflect metabolic processes in SCB at OA, and also the discordant influence of CRP level on PICP level at the relative stability of OC level were demonstrated at the research.The received results allow consider the inflammatory process at OA as a target for preservance of the bone tissue, conditioning the expedience of taking into account the ability of OA basic preparations to realize the control influence on the level of system inflammation. Diacerein that in ESCEO recommendations (2014) is related to the preparations of the 1 step of treatment of patients with OA provides the control on inflammation and stability of osteocalcin level that testifies to the balance of catabolic processes in SCB.Conclusions. At OA the levels of procollagen IC-terminal propeptide (РІСР) and osteocalcin (OC) were not associated with obesity and did not depend on the initial CRP level at the presence of correlation between РІСР level and BMI among patients with OA with the normal body weight and BMI and CRP level among patients with OA in combination with obesity.The absence of reliable dynamics from РІСР side and maintenance of the stable OC level on the background of the reliable anti-inflammatory effect at using diacerein in patients with OA can testify to the compensatory adequacy of reparation processes in SCB

Greater Efficacy and Improved Endothelial Dysfunction in Untreated Type 2 Diabetes with Liraglutide versus Sitagliptin

Objective:The incretin hormone glucagon-like peptide 1 (GLP-1) and its analogs, including the glucagonlike peptide 1 receptor agonist liraglutide, use a simple once-daily regimen and can be easily introduced in the outpatient setting. We compared treatment with liraglutide monotherapy and dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy in patients with untreated type 2 diabetes( T2DM).Methods:This study included 40 outpatients with untreated T2DM who were randomized to receive liraglutide (0.9 mg/day, n=24) or DPP-4 inhibitors (n=16:sitagliptin, 50 mg/day) as initial treatment for 6 months. Glycemic control, urinalysis, blood pressure, body weight, lipid levels, vascular endothelial function, and inflammatory factors were assessed before and after treatment.Results:Significant improvement was observed in HbA1c and fasting blood glucose levels after treatment in both groups;improvements in the liraglutide group were significantly better than in the sitagliptin group. Only the liraglutide group demonstrated significant improvements in blood pressure, low-density lipoprotein cholesterol levels, urinary albumin excretion, flow-mediated dilatation, and high-sensitivity C-reactive protein levels. Linear regression analysis demonstrated a significant negative relation between change in flow-mediated dilatation and high-sensitivity C-reactive protein levels.Conclusion:Liraglutide provided significant glycemic control and improved blood pressure, lipid levels, endothelial function, and inflammatory factors in untreated T2DM. In addition to its impact on blood glucose levels, liraglutide may have beneficial effects on the cardiovascular system in patients with T2DM

Lipid Metabolism

Perilipin 2, also known as Adipose differentiation-relation protein or PLIN2, is a lipid droplet-binding protein present in almost every tissue. The absence of PLIN2 upregulates hepatic very low-density lipoprotein secretion, relieves hepatosteatosis, and improves whole body insulin resistance in mice. Despite of the importance in mediating lipid metabolism, the regulation of PLIN2 itself remains largely unknown. Previous reports have shown that X-box binding protein 1 (XBP1) is an important regulator of lipogenesis. XBP1 is a transcription factor that recognizes and binds to a consensus sequence, 5’-TGACGTGG-3’. Interestingly, when we looked through the promoter region of mouse Plin2 gene, we found that the consensus sequence is present in the Plin2 promoter. Therefore, we hypothesize that XBP1 might directly bind to Plin2 promoter and regulate the Plin2 expression. To test our hypothesis, we will perform the luciferase assay to examine whether the Plin2 promoter activity is regulated by XBP1. We first designed forward and reverse PCR primers, which include BglII and BamHI restriction enzyme sites respectively, to amplify the Plin2 promoter region (from -1100 to +40). We performed PCR and cloned the Plin2 promoter to a TA vector. The TA vector was then sequenced to exclude any point mutations. After sequencing, we sub cloned the Plin2 promoter into a vector containing a luciferase reporter. In the future, we will transfect 293T, a human embryonic kidney cell line, with the Plin2 promoter-luciferase vector we generated. We will compare the Plin2 promoter activity by measuring the luminescence in the presence or absence of XBP1

Intermediary metabolism

Caenorhabditis elegans has orthologs for most of the key enzymes involved in eukaryotic intermediary metabolism, suggesting that the major metabolic pathways are probably present in this species. We discuss how metabolic patterns and activity change as the worm traverses development and ages, or responds to unfavorable external factors, such as temperature extremes or shortages in food or oxygen. Dauer diapause is marked by an enhanced resistance to oxidative stress and a shift toward microaerobic and anaplerotic metabolic pathways and hypometabolism, as indicated by the increased importance of the malate dismutation and glyoxylate pathways and the repression of citric acid cycle activity. These alterations promote prolonged survival of the dauer larva; some of these changes also accompany the extended lifespan of insulin/IGF-1 and several mitochondrial mutants. We also present a brief overview of the nutritional requirements, energy storage and waste products generated by C. elegans

Embryo metabolism : what does it really mean?

The study of early embryo metabolism has fascinated researchers in the field for nearly a century. Herein, we give a brief account of the general features of embryo metabolism and some consideration of the research performed to reach such conclusions. It is becoming increasingly obvious that metabolism informs many fate decisions and outcomes beyond ATP generation, such as DNA methylation, Reactive Oxygen Species generation and cell signaling. We discuss the reasons for studying metabolism in the face of our current knowledge of the effect that the culture environment on the developing embryo and the downstream effects that can cause. The study of in vitro embryo metabolism can also give us insight into developmental perturbations in vivo. The strengths and limitations of the methods we use to study metabolism are reviewed with reference to species-specific fundamental biology and plasticity and we discuss what the future holds for metabolic studies and the unanswered questions that remain

Circadian regulation of glucose, lipid, and energy metabolism in humans.

The circadian system orchestrates metabolism in daily 24-hour cycles. Such rhythms organize metabolism by temporally separating opposing metabolic processes and by anticipating recurring feeding-fasting cycles to increase metabolic efficiency. Although animal studies demonstrate that the circadian system plays a pervasive role in regulating metabolism, it is unclear how, and to what degree, circadian research in rodents translates into humans. Here, we review evidence that the circadian system regulates glucose, lipid, and energy metabolism in humans. Using a range of experimental protocols, studies in humans report circadian rhythms in glucose, insulin, glucose tolerance, lipid levels, energy expenditure, and appetite. Several of these rhythms peak in the biological morning or around noon, implicating earlier in the daytime is optimal for food intake. Importantly, disruptions in these rhythms impair metabolism and influence the pathogenesis of metabolic diseases. We therefore also review evidence that circadian misalignment induced by mistimed light exposure, sleep, or food intake adversely affects metabolic health in humans. These interconnections among the circadian system, metabolism, and behavior underscore the importance of chronobiology for preventing and treating type 2 diabetes, obesity, and hyperlipidemia

One-carbon metabolism in cancer

Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism