State of the Art in the Current Management and Future Directions of Targeted Therapy for Differentiated Thyroid Cancer.

Two-thirds of differentiated thyroid cancer (DTC) patients with distant metastases would be classified as radioactive iodine-refractory (RAIR-DTC), evolving into a poor outcome. Recent advances underlying DTC molecular mechanisms have shifted the therapy focus from the standard approach to targeting specific genetic dysregulations. Lenvatinib and sorafenib are first-line, multitargeted tyrosine kinase inhibitors (TKIs) approved to treat advanced, progressive RAIR-DTC. However, other anti-angiogenic drugs, including single targeted TKIs, are currently being evaluated as alternative or salvage therapy after the failure of first-line TKIs. Combinatorial therapy of mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signalling cascade inhibitors has become a highly advocated strategy to improve the low efficiency of the single agent treatment. Recent studies pointed out targetable alternative pathways to overcome the resistance to MAPK and PI3K pathways' inhibitors. Because radioiodine resistance originates in DTC loss of differentiation, redifferentiation therapies are currently being explored for efficacy. The present review will summarize the conventional management of DTC, the first-line and alternative TKIs in RAIR-DTC, and the approaches that seek to overcome the resistance to MAPK and PI3K pathways' inhibitors. We also aim to emphasize the latest achievements in the research of redifferentiation therapy, immunotherapy, and agents targeting gene rearrangements in advanced DTC.

Weight Loss and Late Complications after Silastic Ring Vertical Gastroplasty. A 10 Year Follow-up.

BACKGROUND AND AIM: Severe obesity is a public health care system challenge that requires bariatric surgery. Among the plethora of bariatric surgery techniques silastic ring vertical gastroplasty (SRVG) is a safe and efficient restrictive method that has been successfully used previously. However, it's performance by open approach has been abandoned and replaced by other methods using the laparoscopic method. The aim of the present study was to investigate patients with severe obesity submitted to open SRVG and to report our results over a period of 10 years in terms of weight loss, late complications and surgical re-interventions. MATERIAL AND METHODS: 112 severely obese patients submitted to open SRVG between years 2008- 2009 were investigated retrospectively for body mass index (BMI), percent excess BMI loss (%EBMIL), late surgical complications and reoperations. 41.96% of the patients were followed up 10 years after SRVG. Results: The initial mean BMI was 47.38 +- 7.59 kg/m2 and dropped statistically significant (p 0.001) to 31.05 +- 6.54 kg/m2 by the first year after SRVG. The mean BMI was rather stable along the first 5 years after SRVG when it started to increase gradually, reaching 35.93 +- 7.20 kg/m2 by the 10th year of follow-up when it remained still significantly lower (p 0.001) as compared to the mean baseline value. The %EBMIL was 79% at one year after surgery and reached 51% by the 10th year of follow-up. The most frequent late complications after SRVG were stoma stenosis (8.92%), enlargement of the stoma (8.03%) and incisional hernia (3.36%). As a consequence of stoma stenosis the ring has been removed in all cases. In 2 cases, after the ring removal, the patients underwent gastric bypass. CONCLUSION: SRVG is a safe and efficient restrictive technique of bariatric surgery open to many options to be revised, leading to a successful sustained long term weight loss and maintenance. Stoma stenosis, enlargement of the stoma and incisional hernia are the most frequent late complications after SRVG requesting reoperations.

Bioactive Compounds Extracted from Tomato Processing by-Products as a Source of Valuable Nutrients.

Alongside paper, plastic, metal and glass, an important segment in the recycling area is represented by the wastes of different vegetal processing industries. These by-products gained interest lately, in the context of food waste prevention and growing population number. In the tomato processing industry approximately, 8.5 million tons of wastes are generated globally, each year. The present study highlights the valuable bioactive constituents as lycopene, beta-carotene, glutamic acid or aspartic acid from the by-products of tomato processing industries, which can be revalorized as incorporated nutrients in functional foods. Tomato consumption is directly associated with the prevention of different chronic diseases and carcinogenesis, however the carotenoids bioavailability is a key factor in this process. Further, fiber content together with protein content of tomato seeds and benefits of their consumption are emphasized. Value-added food products obtained by tomato peels or seeds addition are exemplified in this review (bakery, meat products, pasta and noodles, dairy and oil products as well as jams and functional ice cream), in order to embrace next prototypes that can transform vegetal by-products in functional nutrients.

Utilization of biodiesel derived-glycerol for 1,3-PD and citric acid production.

Today, biofuels represent a hot topic in the context of petroleum and adjacent products decrease. As biofuels production increase, so does the production of their major byproduct, namely crude glycerol. The efficient usage of raw glycerol will concur to the biodiesel viability. As an inevitable waste of biodiesel manufacturing, glycerol is potentially an attractive substrate for the production of value-added products by fermentation processes, due to its large amounts, low cost and high degree of reduction. One of the most important usages of glycerol is its bioconversion through microbial fermentation to value-added materials like 1,3-propanediol and citric acid. There is a considerable industrial interest in 1,3-propanediol and citric acid production based on microbial fermentations, as it seems to be in competition with traditional technologies utilized for these products. In the present work, yields and concentrations of 1,3-propanediol and citric acid registered for different isolated strains are also described. Microbial bioconversion of glycerol represents a remarkable choice to add value to the biofuel production chain, allowing the biofuel industry to be more competitive. The current review presents certain ways for the bioconversion of crude glycerol into citric acid and 1,3-propanediol with high yields and concentrations achieved by using isolated microorganisms.

Occurrence of Types A and B Trichothecenes in Cereal Products Sold in Romanian Markets.

In view of the frequent occurrences of mycotoxins in cereals, this study assessed the presence of trichothecenes in 121 samples from Romanian markets. These samples were divided into five groups based on product type: (1) bread and bakery products containing white flour, (2) half-brown bread with whole wheat flour, (3) brown bread containing rye flour, (4) pasta, and (5) raw wheat. Gas Chromatography-Mass Spectrometry was used to detect 13 different mycotoxins, which included the Type A compounds HT-2 toxin and T-2 toxin, as well as the Type B compounds deoxynivalenol and nivalenol. Results indicated trichothecene contamination in 90.08% of our samples, with deoxynivalenol predominating by at least 78% in each examined group. Co-occurrence of three or four trichothecenes were found in 23.85% of our samples. Our study underscores the necessity of consistent monitoring of staple foods to prevent the intake of harmful trichothecenes by consumers.

Bovine delta papillomavirus E5 oncoprotein negatively regulates the cGAS-STING signaling pathway in cattle in a spontaneous model of viral disease.

Persistent infection and tumorigenesis by papillomaviruses (PVs) require viral manipulation of various cellular processes, including those involved in innate immune responses. The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes (cGAS-STING) pathway has emerged as an essential innate immune sensing system, that recognizes DNA and trigger potent antiviral effector responses. In this study, we found that bovine PV (BPV) E5 protein, the major oncoprotein of bovine delta PVs, interacts with STING but not with cGAS in a spontaneous BPV infection of neoplastic urothelial cells of cattle. Real-time RT-PCR revealed a significant reduction in both cGAS and STING transcripts in E5-expressing cells. Furthermore, western blot (WB) analysis failed to detect any variation in the expression of interferon-inducible protein 16 (IFI16), an upstream effector of the STING pathway. A ternary complex composed of E5/STING/IFI16 was also observed. Co-immunoprecipitation studies showed that STING interacts with a protein network composed of total and phosphorylated TANK-binding kinase 1 (TBK1), total and phosphorylated interferon regulatory factor 3 (IRF3), IRF7, IKKα, IKKß, IKKϵ, ELKS, MEKK3, and TAK1. RT-qPCR revealed a significant reduction in TBK1 mRNA levels in BPV-infected cells. WB analysis revealed significantly reduced expression levels of pTBK1, which is essential for the activation and phosphorylation of IRF3, a prerequisite for the latter to enter the nucleus to activate type 1 IFN genes. WB also revealed significantly down-expression of IKKα, IKKß, IKKϵ, and overexpression of IRF7, ELKS, MEKK3, and TAK1in BPV-positive urothelial cells compared with that in uninfected healthy cells. Phosphorylated p65 (p-p65) was significantly reduced in both the nuclear and cytosolic compartments of BPV-infected cells compared with that in uninfected urothelial cells. Our results suggest that the innate immune signaling pathway mediated by cGAS-STING is impaired in cells infected with BPV. Therefore, effective immune responses are not elicited against these viruses, which facilitates persistent viral infection and subsequent tumorigenesis.

Nutritional status prior to bariatric surgery for severe obesity: a review.

Obesity pandemic represents a threat to public health of paramount importance. Bariatric surgery represents the most effective and long-lasting treatment for severe obesity so far. The nutritional status of obese patients seeking bariatric surgery is impaired prior to surgery because of prevalent nutritional deficiencies. In addition, excess micronutrient levels may also occur, although this finding is not common. The onset of nutritional anomalies encountered in bariatric surgery candidates might stem from the following: obesity itself, poor quality food choices, preoperative weight loss or insufficient/excessive preoperative oral supplementation with vitamins and minerals. Nutritional management should begin preoperatively and should include a comprehensive assessment in order to identify those patients with clinical or subclinical deficiencies and hypervitaminoses. This paper provides background information on the nutritional status of bariatric surgery candidates, as well as on the prevalence and clinical significance of the most common micronutrient deficiencies and excess levels reported preoperatively among these patients.

Bovine Delta Papillomavirus E5 Oncoprotein Interacts With TRIM25 and Hampers Antiviral Innate Immune Response Mediated by RIG-I-Like Receptors.

Persistent infection and tumourigenesis by papillomaviruses (PVs) require viral manipulation of various of cellular processes, including those involved in innate immune responses. Herein, we showed that bovine PV (BPV) E5 oncoprotein interacts with a tripartite motif-containing 25 (TRIM25) but not with Riplet in spontaneous BPV infection of urothelial cells of cattle. Statistically significant reduced protein levels of TRIM25, retinoic acid-inducible gene I (RIG-I), and melanoma differentiation-associated gene 5 (MDA5) were detected by Western blot analysis. Real-time quantitative PCR revealed marked transcriptional downregulation of RIG-I and MDA5 in E5-expressing cells compared with healthy urothelial cells. Mitochondrial antiviral signalling (MAVS) protein expression did not vary significantly between diseased and healthy cells. Co-immunoprecipitation studies showed that MAVS interacted with a protein network composed of Sec13, which is a positive regulator of MAVS-mediated RLR antiviral signalling, phosphorylated TANK binding kinase 1 (TBK1), and phosphorylated interferon regulatory factor 3 (IRF3). Immunoblotting revealed significantly low expression levels of Sec13 in BPV-infected cells. Low levels of Sec13 resulted in a weaker host antiviral immune response, as it attenuates MAVS-mediated IRF3 activation. Furthermore, western blot analysis revealed significantly reduced expression levels of pTBK1, which plays an essential role in the activation and phosphorylation of IRF3, a prerequisite for the latter to enter the nucleus to activate type 1 IFN genes. Our results suggested that the innate immune signalling pathway mediated by RIG-I-like receptors (RLRs) was impaired in cells infected with BPVs. Therefore, an effective immune response is not elicited against these viruses, which facilitates persistent viral infection.

Relationship between 25 Hydroxyvitamin D, Overweight/Obesity Status, Pro-Inflammatory and Oxidative Stress Markers in Patients with Type 2 Diabetes: A Simplified Empirical Path Model.

Vitamin D deficiency is highly prevalent in patients with overweight/obesity and type 2 diabetes (T2DM). Herein, we investigated the relationship between vitamin D status and overweight/obesity status, insulin resistance (IR), systemic inflammation as well as oxidative stress (OS). Anthropometric and laboratory assessments of 25-hydroxyvitamin D (25(OH)D) and glycemic, pro-inflammatory and OS biomarkers were performed in a sample of 47 patients with T2DM who were divided into categories based on overweight and degree of obesity. The main findings were: the overweight/obesity status correlated negatively with the degree of serum 25(OH)D deficiency (ρ = -0.27) with a trend towards statistical significance (p = 0.069); the homeostasis model assessment of insulin resistance (HOMA-IR) was significantly different (p = 0.024) in patients with 25(OH)D deficiency, as was total oxidant status (TOS) and oxidative stress index (OSI) in patients with severe serum 25(OH)D deficiency as compared to those with 25(OH)D over 20 ng/mL (TOS: p = 0.007, OSI: p = 0.008); and 25(OH)D had a negative indirect effect on TOS by body mass index (BMI), but BMI was not a significant mediator of the studied relationship. In a setting of overweight and increasing degree of obesity, patients with T2DM did not display decreasing values of 25(OH)D. Subjects with the lowest values of 25(OH)D presented the highest values of BMI. Patients with 25(OH)D deficiency were more insulin resistant and showed increased OS but no elevated systemic inflammation. The negative effect of 25(OH)D on TOS did not seem to involve BMI as a mediator.

Obesity-Related Metabolic Dysfunction in Dairy Cows and Horses: Comparison to Human Metabolic Syndrome.

Obesity has become a serious health problem with frequent occurrence both in human and animal populations. It is estimated that it may affect over 85% of the human population and 70-80% of horses and cows by 2030. Fat cow syndrome (FCS) is a combination of metabolic, digestive, infectious, and reproductive disorders that affects obese periparturient dairy cows, and occurs most frequently in loose-housing systems, where periparturient and dry cows are fed and managed in one group disregarding the lactation stages. Equine metabolic syndrome (EMS) was named after human metabolic syndrome (MetS) and has insulin dysregulation as a central and consistent feature. It is often associated with obesity, although EMS may occur in a lean phenotype as well. Other inconsistent features of EMS are cardiovascular changes and adipose dysregulation. Laminitis is the main clinical consequence of EMS. MetS holds a 30-years old lead in research and represents a clustering of risk factors that comprise abdominal obesity, dyslipidemia, hypertension, and hyperglycemia (impaired fasting glucose or type 2 diabetes mellitus-T2DM), which are associated with doubled atherosclerotic cardiovascular disease risk, and a 5-fold increased risk for T2DM. The main aim of this review is to provide critical information for better understanding of the underlying mechanisms of obesity-related metabolic dysfunction in animals, especially in cows and horses, in comparison with MetS. Human medicine studies can offer suitable candidate mechanisms to fill the existing gap in the literature, which might be indispensable for owners to tackle FCS, EMS, and their consequences.

Bariatric Surgery in Obesity: Effects on Gut Microbiota and Micronutrient Status.

Obesity is associated with reduced gut microbial diversity and a high rate of micronutrient deficiency. Bariatric surgery, the therapy of choice for severe obesity, produces sustained weight loss and improvements in obesity-related comorbidities. Also, it significantly alters the gut microbiota (GM) composition and function, which might have an important impact on the micronutrient status as GM is able to synthesize certain vitamins, such as riboflavin, folate, B12, or vitamin K2. However, recent data have reported that GM is not fully restored after bariatric surgery; therefore, manipulation of GM through probiotics represents a promising therapeutic approach in bariatric patients. In this review, we discuss the latest evidence concerning the relationship between obesity, GM and micronutrients, the impact of bariatric surgery on GM in relation with micronutrients equilibrium, and the importance of the probiotics' supplementation in obese patients submitted to surgical treatment.

Quercetin and curcumin effects in experimental pleural inflammation.

BACKGROUND: The inflammatory mechanisms occur with the highest prevalence in pulmonary pathology in addition to oxidative stress and activation of intracellular signaling pathways. The oxidative stress represents the imbalance between pro-oxidants and antioxidants which can lead to the activation of the oxidative mechanisms with noxious potential to the body. Therefore, finding a therapy that would counteract the injurious effects of free radicals and inflammation is highly attractive. Quercetin is the most active flavonoid, with important anti-inflammatory and antioxidant effects, while curcumin has antioxidant effects that are similar to the standard antioxidants and exerts direct anti-inflammatory activity. AIMS: The aim of this study is to evaluate the antioxidant effects of quercetin and curcumin on an experimental model, pleural inflammation induced by carrageenan. METHODS: Eight groups of adult male rats were used: Ia and Ib - control groups, IIa and IIb - with carrageenan administration, IIIa and IIIb - received curcumin and carrageenan, IVa and IVb - quercetin and carrageenan administration. Blood and lung samples were taken at 4 hours (Ia, IIa, IIIa, IVa groups) and at 24 hours (Ib, IIb, IIIb, IVb groups) after carrageenan injection. RESULTS: At 4 and at 24 hours, curcumin and quercetin have shown protective systemic effects, decreasing significantly the oxidative stress (malondialdehyde level) and stimulating significantly the antioxidant protection (ceruloplasmin and glutathione levels) compared to the group that received only carrageenan. In the lungs, at 4 hours, the redox misbalance was significantly reduced only in animals that were treated with quercetin, modifications that were not observed at 24 hours. CONCLUSIONS: In serum, curcumin presented higher antioxidant effects, compared to quercetin. In lungs, quercetin administration showed superior beneficial effects, but only temporarily.

Metabolically Healthy Obesity and Bariatric Surgery.

A peculiar category of persons with obesity lacking common metabolic disturbances has been depicted and termed as metabolically healthy obesity (MHO). Yet, although MHO patients are free of obesity-associated complications, they might not be entirely precluded from developing cardio-metabolic disorders. Among patients with morbid obesity (MO) who are referred to bariatric surgery, a subset of metabolically healthy MO (MHMO) has been identified and the question arises if these patients would benefit from surgery in terms of mitigating the peril of cardio-metabolic complications. We revisited the pathophysiological mechanisms that define MHO, the currently available data on the cardio-metabolic risk of these patients and finally we reviewed the benefits of bariatric surgery and the urge to better characterize MHMO before submission to surgery.

Solid-State Yeast Fermented Wheat and Oat Bran as A Route for Delivery of Antioxidants.

The purpose of our study was to evaluate the potential of solid-state yeast fermentation (SSYF) in improving the phenolic acid content and composition, and the antioxidant activity of commercial wheat bran (WB) and oat bran (OB). The ultrasound-assisted methanolic extracts were compared for their total phenolic content (TPC), phenolics composition, and in vitro antioxidant activity in order to study the effect of fermentation time on the chemical profile and activity of bioactive compounds. The comparative analysis revealed significant differences (p < 0.05) between days of fermentation (0 through 6). The highest TPCs were obtained on day 3 for WB (0.84 ± 0.05 mg of gallic acid equivalents [GAE]/g dry weight [DW]), and on day 4 for OB (0.45 ± 0.02 mg GAE/g DW). The highest relative percentage increase in the phenolics concentration of WB was also registered on day 3 (ferulic acid +56.6%, vanillic acid +259.3%, dihydroxybenzoic acids +161.2%, apigenin-glucoside +15.3%); for OB, this was observed on day 4 (avenanthramide 2f +48.5%, ferulic acid +21.2%). Enhanced antioxidant activities were significantly correlated with the highest TPCs. Our results suggest that SSYF may be a useful procedure for enrichment of antioxidants in cereal bran, considering the design of different functional foods and nutraceuticals.

Screening of Ten Tomato Varieties Processing Waste for Bioactive Components and Their Related Antioxidant and Antimicrobial Activities.

Global tomato production is currently around 180 million tons, of which more than a quarter undergoes processing. The removed peels, seeds, and vascular tissues usually end up in landfills, creating environmental pollution. In order to highlight the alternative use of these vegetal wastes, our study investigated 10 tomato varieties in terms of carotenoids content, phenolic composition, and their related antioxidant and antimicrobial activities. Tomato peels extracts were screened by high performance liquid chromatography with diode-array detection (HPLC/DAD) for qualitative and quantitative analyses. The extracts were tested against six bacterial strains to determine their antimicrobial effect; the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay was applied to estimate their antioxidant capacity. Total carotenoids content was significantly higher in Taranești roz, a local variety (5.31 ± 0.12 mg/100 g DW), while Mirsini, a commercial hybrid, presented significantly higher total phenolic content (155 ± 2 mg/100 g DW) compared to the mean value of all analyzed samples. The methanolic extracts of tomato peels presented acceptable antimicrobial activity against Staphilococcus aureus and Bacillus subtilis, and the mean antioxidant activity was 201 ± 44 µmol Trolox/100 g DW tomato peels. Considering that tomato peels have lycopene, ß-carotene, lutein, and different phenolic compounds in their composition, tomato industrial by-products could represent a source of natural bioactive molecules with applicability in nutraceuticals and food industry.

Regeneration of Denervated Skeletal Muscles - Brunelli's CNS-PNS Paradigm.

The restoration of voluntary muscle activity in posttraumatic paraplegia in both animal experiments and other clinical applications requires reproducibility of a technically-demanding microsurgical procedure, limited by physicians' understanding of Brunelli's spinal cord grafting paradigm. The insufficient clinical investigation of the long-term benefits of the CNS-PNS graft application warrants additional inquiry. The objective of this study is to explore the potential benefits of the first replicated, graft-induced neuroregeneration of denervated skeletal muscle regarding long-term clinical outcomes and to investigate the effect of Cerebrolysin on neuromodulation. A randomized study evaluating 30 rats, approved by the National Animal Ethics Advisory Committee was performed. The medication was administered postoperatively. For 14 days, 12 rats received Cerebrolysin (serum), 11 received NaCl 0.9% (shams), and 7 were controls. For microsurgery, the lateral corticospinal tract T10 was grafted to the denervated internal obliquus abdominal muscle. On day 90, intraoperative proof of reinnervation was observed. On day 100, 15 rats were euthanized for fixation, organ removal, and extensive histology-morphology examination, and the Wei-Lachin statistical procedure was employed. After an open revision of 16 rats, 8 were CMAP positive. After intravenous Vecuronium application, two (Cerebrolysin, NaCl) out of two rats showed an incomplete compound muscle action potential (CMAP) loss due to glutamatergic and cholinergic co-transmission, while two others showed a complete loss of amplitude. Cerebrolysin medication initiated larger restored muscle fiber diameters and less scarring. FB+ neurons were not observed in the brain but were observed in the Rexed laminae. Brunelli's concept was successfully replicated, demonstrating the first graft induced existence of cholinergic and glutamatergic neurotransmission in denervated grafted muscles. Statistics of the histometric count of muscle fibers revealed larger fiber diameters after Cerebrolysin. Brunelli's CNS-PNS experimental concept is suitable to analyze graft-neuroplasticity focused on the voluntary restoration of denervated skeletal muscles in spinal cord injury. Neuroprotection by Cerebrolysin is demonstrated.

Phytochemical Analysis of Anti-Inflammatory and Antioxidant Effects of Mahonia aquifolium Flower and Fruit Extracts.

Oxidative stress and inflammation are interlinked processes. The aim of the study was to perform a phytochemical analysis and to evaluate the antioxidant and anti-inflammatory activities of ethanolic Mahonia aquifolium flower (MF), green fruit (MGF), and ripe fruit (MRF) extracts. Plant extract chemical composition was evaluated by HLPC. A DPPH test was used for the in vitro antioxidant activity. The in vivo antioxidant effects and the anti-inflammatory potential were tested on a rat turpentine oil-induced inflammation, by measuring serum nitric oxide (NOx) and TNF-alpha, total oxidative status (TOS), total antioxidant reactivity (TAR), oxidative stress index (OSI), 3-nitrothyrosine (3NT), malondialdehyde (MDA), and total thiols (SH). Extracts were administrated orally in three dilutions (100%, 50%, and 25%) for seven days prior to inflammation. The effects were compared to diclofenac. The HPLC polyphenol and alkaloid analysis revealed chlorogenic acid as the most abundant compound. All extracts had a good in vitro antioxidant activity, decreased NOx, TOS, and 3NT, and increased SH. TNF-alpha was reduced, and TAR increased only by MF and MGF. MDA was not influenced. Our findings suggest that M. aquifolium has anti-inflammatory and antioxidant effects that support the use in primary prevention of the inflammatory processes.

Effects of sleeve gastrectomy on insulin resistance.

BACKGROUND AND AIM: Obesity is a major risk factor for the onset of insulin resistance (IR), hyperinsulinemia and type 2 diabetes mellitus (T2DM) Evidence data has proven that beyond important weight loss bariatric surgery especially Roux-en-Y gastric bypass (RYGB) and bilio-pancreatic diversion (BPD) leads to significant early reduction of insulinemia and of IR calculated through the homeostatic model assessment (HOMA-IR), independently of fat mass decrease. Sleeve gastrectomy (SG) is now used as a sole weight loss operation with good results. Therefore, the aim of the present study was to investigate the early changes of fasting blood glucose, insulin and HOMA-IR in a group of morbidly obese (MO) patients i.e. at 7, 30 and 90 days after SG. METHODS: The study included 20 MO patients (7 male and 13 female) submitted to SG. Anthropometrical (weight, body mass index -BMI, percent excess BMI loss -%EBMIL) and biochemical (plasma glucose, insulin and calculated HOMA-IR ) evaluation were performed before and at 7, 30 and 90 days after SG. In addition, a second group of 10 normal weight healthy subjects with a BMI ranging form 19 kg/m(2) to 23.14 kg/m(2), matched for age and gender was investigated. RESULTS: Plasma glucose (p=0.018), insulin (p=0.004) and HOMA-IR (p=0.006) values were statistically different between the studied groups. After surgery, at every follow-up point, there were statistically different weight and BMI mean values relative to the operation day (p<0.003). BMI, decreased at 7 days (estimated reduction=2.79; 95% CI:[2.12;3.45]), at 30 days (estimated reduction=5.65; 95% CI:[3.57;7.73]) and at 90 days (estimated reduction=10.88; 95% CI:[7.35;14.41]) respectively after SG. We noted a tendency toward statistical significant change of mean insulin values at 7 days after surgery (corrected p=0.075), no statistical change at 30 days (corrected p=0.327) and a significant change at 90 days (corrected p=0.027) after SG as compared to baseline. There was a significant change in mean values of HOMA-IR at 30 days (corrected p=0.009) and at 90 days (corrected p=0.021) after the operation day. CONCLUSIONS: The present study showed important early changes consisting in reductions of mean values of plasma insulin and HOMA-IR after SG.

Metabolic Mechanisms in Obesity and Type 2 Diabetes: Insights from Bariatric/Metabolic Surgery.

Obesity and the related diabetes epidemics represent a real concern worldwide. Bariatric/metabolic surgery emerged in last years as a valuable therapeutic option for obesity and related diseases, including type 2 diabetes mellitus (T2DM). The complicated network of mechanisms involved in obesity and T2DM have not completely defined yet. There is still a debate on which would be the first metabolic defect leading to metabolic deterioration: insulin resistance or hyperinsulinemia? Insight into the metabolic effects of bariatric/metabolic surgery has revealed that, beyond weight loss and food restriction, other mechanisms can be activated by the rearrangements of the gastrointestinal tract, such as the incretinic/anti-incretinic system, changes in bile acid composition and flow, and modifications of gut microbiota; all of them possibly involved in the remission of T2DM. The complete elucidation of these mechanisms will lead to a better understanding of the pathogenesis of this disease. Our aim was to review some of the metabolic mechanisms involved in the development of T2DM in obese patients as well as in the remission of this condition in patients submitted to bariatric/metabolic surgery.

Increased chemerin and decreased omentin-1 levels in morbidly obese patients are correlated with insulin resistance, oxidative stress and chronic inflammation.

BACKGROUND AND AIM: Morbid obesity represents a proinflammatory and pro-oxidative state associated with dysregulation of adipokines. We aimed to evaluate the circulating levels of chemerin and omentin-1 in morbidly obese (MO) patients and to investigate the relationship between these two adipokines and between each of them and anthropometric, metabolic, oxidative stress and chronic inflammatory parameters. MATERIAL AND METHODS: 32 MO patients and 20 controls were investigated in this study. Anthropometric, metabolism parameters, inflammatory markers, oxidative stress indicators as well as chemerin and omentin-1 were measured. RESULTS: Serum levels of chemerin were increased while omentin-1 levels were decreased in MO patients when compared with controls. Chemerin correlated positively with insulin, HOMA-IR, LDL cholesterol and negatively with total antioxidant response. Omentin-1 correlated negatively with tumor necrosis factor alpha and total cholesterol. In a multiple linear stepwise regression analysis we learnt that only HOMA-IR (ß=0.70, p<0.001), total cholesterol (ß=0.42, p<0.001) and triglycerides (ß=0.31, p<0.05) remained significantly associated with chemerin changes. Using the same analysis we noticed that total cholesterol (ß=-0.71, p<0.001), fasting glucose (ß= -0.40, p<0.05) and body mass index (BMI) (ß= -0.38, p<0.05) were considered to be significant predictors for omentin-1 changes. CONCLUSIONS: Chemerin and omentin-1 synthesis was dysregulated in MO patients. Chemerin might play a role in insulin resistance and oxidative stress. Chemerin changes seemed to be predicted mainly by insulin resistance. Omentin-1 levels were inversely associated with chronic inflammation and dyslipidemia while the main modulating factors seemed to be dyslipidemia, hyperglycemia and BMI.