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(1) Vitamin D deficiency and changes in the endocrine system may stimulate systemic inflammation. VDR expression and the vitamin D concentration decrease with age, which is important in postmenopausal women for whom estrogen deficiency causes rapid bone loss. This group is, moreover, particularly at risk of developing atherosclerosis and its adverse consequences, such as chronic inflammation. The aim of this study was to assess the differentiation by the VDR genotype of the risk factors for so-called chronic low-grade inflammation and metabolic disorders. (2) We studied the differences between the anthropometric, metabolic, and inflammation parameters of VDR genotypes for Apa-I, Bsm-I, Fok-I, and Taq-I in a sample of 321 women aged 50–60 from an ethnically homogeneous urban population in Poland. (3) The TT Taq-I genotype presented a significantly higher rate of insulin resistance (HOMA) and lower serum levels of adiponectin than the other two genotypes. The AA genotype of the Bsm-I polymorphism was associated with a more atherogenic serum profile and significantly higher LDL and LDL/HDL values and Castelli Index. (4) Chronic low-grade inflammation was associated with the TT Taq-I genotype and presented a higher rate of insulin resistance. The AA genotype of the Bsm-I polymorphism presented a more atherogenic serum lipid profile and, therefore, a higher risk of developing cardiovascular disease.

Background: The side effects of antipsychotics (APs), related to weight gain and metabolic disturbances, can contribute to the health burden of psychotic people. Objective: To explore a) the level of adherence to the Mediterranean Diet (MedDiet) and consumption of fermented foods by first episode of psychosis (FEPs) patients taking APs, in comparison to matched -for age and BMI- healthy controls (HCs), and b) the effect of this dietary pattern on the biochemical and metabolic profile of FEPs. Method: The study population consisted of 33 FEPs treated with APs for less than 5 years, with no history of other chronic diseases, and an equal number of HCs. The FEPs were classified into two subgroups, according to their AP medication, depending on the documented risk of weight gain. A validated questionnaire for the adherence to Mediterranean diet and a food frequency questionnaire for selected fermented foods were completed by FEPs and HC. Anthropometric data and blood measurements were recorded for all participants. Results and conclusions: The FEPs showed a relevant lower overall adherence to the MedDiet, but no differences in consumption of fermented foods. Type of antipsychotic therapy uncovered differences in platelet count, vitamin B12, HDL and glucose (p < 0.05) between the subgroups of FEPs and HCs, although no values were abnormal. The MedDiet score was found to act as a prognostic factor for abnormal glucose levels in FEPs treated with APs associated with weight gain (p = 0.04). These results need to be confirmed by observations after long term adherence to MedDiet.

Metabolic disturbances and obesity are major cardiovascular risk factors in patients with schizophrenia, resulting in a higher mortality rate and shorter life expectancy compared with those in the general population. Although schizophrenia and metabolic disturbances may share certain genetic or pathobiological risks, antipsychotics, particularly those of second generation, may further increase the risk of weight gain and metabolic disturbances in patients with schizophrenia. This review included articles on weight gain and metabolic disturbances related to antipsychotics and their mechanisms, monitoring guidelines, and interventions. Nearly all antipsychotics are associated with weight gain, but the degree of the weight gain varies considerably. Although certain neurotransmitter receptor-binding affinities and hormones are correlated with weight gain and specific metabolic abnormalities, the precise mechanisms underlying antipsychotic-induced weight gain and metabolic disturbances remain unclear. Emerging evidence indicates the role of genetic polymorphisms associated with antipsychotic-induced weight gain and antipsychotic-induced metabolic disturbances. Although many guidelines for screening and monitoring antipsychotic-induced metabolic disturbances have been developed, they are not routinely implemented in clinical care. Numerous studies have also investigated strategies for managing antipsychotic-induced metabolic disturbances. Thus, patients and their caregivers must be educated and motivated to pursue a healthier life through smoking cessation and dietary and physical activity programs. If lifestyle intervention fails, switching to another antipsychotic drug with a lower metabolic risk or adding adjunctive medication to mitigate weight gain should be considered. Antipsychotic medications are essential for schizophrenia treatment, hence clinicians should monitor and manage the resulting weight gain and metabolic disturbances.

Uvod: Sindrom ponovnega hranjenja predstavlja hude elektrolitske in presnovne motnje pri podhranjenih bolnikih v začetku ponovnega hranjenja po obdobju stradanja. Pogosto ostane nediagnosticiran, kar je nevarno, saj je sindrom ponovnega hranjenja lahko življenjsko ogrožajoče stanje. Namen: Namen diplomskega dela je predstaviti najnovejše smernice za ocenjevanje, zdravljenje in preprečevanje sindroma ponovnega hranjenja. Metode dela: Uporabljena je bila deskriptivna metoda dela s pregledom literature. Iskanje literature je potekalo preko spletnega portala Digitalne knjižnice Univerze v Ljubljani v mednarodnih spletnih bazah Medline/PubMed, Cinahl, Cochrane Library ter s pomočjo kataloške baze podatkov COBIS.SI. V končno analizo je bilo vključenih pet člankov. Rezultati: Prikazani rezultati petih člankov visoke kakovosti po hierarhiji dokazov se osredotočajo predvsem na bolnike z motnjami hranjenja ter odrasle starejše, zaradi kroničnih stanj v bolnišničnem okolju. Dva članka se navezujeta na ocenjevanje sindroma ponovnega hranjenja s pomočjo označevalca – inzulinu podobnega rastnega faktorja in računalniškega strojnega modela za napovedovanje hipofosfatemije. Ugotovili so, da sta oba načina učinkovita za napovedovanje tveganja pred začetkom ponovnega parenteralnega hranjenja bolnika. Trije članki pa opisujejo načine ustrezne prehranske terapije podhranjenih bolnikov pri ponovnem peroralnem in enteralnem hranjenju. Visok energijski vnos hrane ne poveča pojavnosti sindroma ponovnega hranjenja ali umrljivosti pri teh bolnikih. Na incidenco sindroma ponovnega hranjenja in pojav hipofosfatemije ne vpliva visok ali nizek kalorični vnos hrane. Ugotovili so, da je lahko visok kalorični vnos hrane varen z dodajanjem tiamina, spremljanjem potreb bolnika po kaliju, fosfatu in tekočini v serumu. Parenteralen vnos hrane je potrebno izračunati glede na bolnikove potrebe in priporočene dnevne energijske vnose. Razprava in zaključek: Presejalni testi za prepoznavanje znakov in simptomov sindroma ponovnega hranjenja so nenatančni, zato je diagnosticiranje bolnikov oteženo. Za prepoznavanje ogroženih bolnikov za sindrom ponovnega hranjenja je potrebno ozaveščanje zdravstvenih delavcev o resnosti zdravstvenega problema pri bolnikih s tveganjem za sindrom ponovnega hranjenja. Protokoli namenjeni preprečevanju in učinkovitemu obvladovanju sindroma ponovnega hranjenja so še vedno velik izziv za kakovostno zdravstveno oskrbo podhranjenih bolnikov. Introduction: Refeeding syndrome represents a severe electrolyte disturbance and metabolic abnormalities in malnourished patients after the start of refeeding, after a period of starvation. It is often left undiagnosed which is dangerous, as the refeeding syndrome can be a life-threatening condition. Purpose: The purpose of this work is to present the latest guidelines for the assessment, treatment and prevention of SPH. Methods: A descriptive method of working with a review of the literature was used. The search for literature took place via the web portal of the Digital Library of the University of Ljubljana in the international online databases Medline / PubMed, Cinahl, Cochrane Library and with the help of the catalog database COBIS.SI. Five articles were included in the final analysis. Results: The presented results of five high-quality articles by hierarchy of evidence focus mainly on patients with eating disorders and older adults due to chronic medical conditions in a hospital setting. Two articles relate the assessment of refeeding syndrome using the marker insulin-like growth factor and a machine learning model for predicting hypophosphatemia. They concluded that both methods are effective for predicting risk before restarting parenteral nutrition. Three articles, however, describe the methods of adequate nutritional therapy of malnourished patients with repeated oral and enteral feeding. High energy food intake does not increase the incidence of refeeding syndrome or mortality in these patients. The incidence of refeeding syndrome and the occurrence of hypophosphatemia are not influenced by high or low caloric food intake. They concluded that high caloric food intake can be made safe by supplementing thiamine, monitoring the patient's serum potassium, phosphate, and fluid requirements. Parenteral food intake should be calculated according to the patient's needs and recommended daily energy intake. Discussion and conclusion: Screening tests for signs and symptoms of refeeding syndrome are imprecise, making diagnosing patients difficult. In order to identify patients at risk for refeeding syndrome, it is necessary to raise awareness among healthcare professionals about the severity of the medical problem in patients at risk for refeeding syndrome. Protocols aimed at preventing and effectively managing refeeding syndrome are still a major challenge for quality medical care of malnourished patients.

Long-chain polyunsaturated fatty acids n-3 series (n-3 LC-PUFAs), especially eicosapentaenoic and docosahexaenoic acids, are known to exert preventive effects on obesity and metabolic syndrome. Mainly consumed in the form of fish oil, LC-PUFAs n-3 are also found in significant quantities in other sources such as certain microalgae. The aim of this study was to evaluate the effects of Diacronema lutheri (Dia), a microalga rich in n-3 LC-PUFAs, on metabolic disorders associated with obesity. Three groups of male Wistar rats (n = 6 per group) were submitted for eight weeks to a standard diet or high-fat and high-fructose diet (HF), supplemented or not with 12% of Dia (HF-Dia). Compared to HF rats, HF-Dia rats showed a 41% decrease in plasma triacylglycerol (TAG) and an increase in plasma cholesterol (+35%) as well as in high-density lipoprotein cholesterol (+51%) without change to low-density lipoprotein cholesterol levels. Although fasting glycemia did not change, glucose and insulin tolerance tests highlighted an improvement in glucose and insulin homeostasis. Dia supplementation restored body weight and fat mass, and decreased levels of liver TAG (−75%) and cholesterol (−84%). In HF-Dia rats, leptin was decreased (−30%) below the control level corresponding to a reduction of 68% compared to HF rats. Similarly, the anti-inflammatory cytokines interleukin-4 (IL-4) and IL-10 were restored up to control levels, corresponding to a 74% and 58% increase in HF rats, respectively. In contrast, the level of IL-6 remained similar in the HF and HF-Dia groups and about twice that of the control. In conclusion, these results indicated that the D. lutheri microalga may be beneficial for the prevention of weight gain and improvement in lipid and glucose homeostasis.

Obesity and overnutrition induce inflammation, leptin-, and insulin resistance in the hypothalamus. The mediobasal hypothalamus responds to exercise enabling critical adaptions at molecular and cellular level that positively impact local inflammation. This review discusses the positive effect of exercise on obesity-induced hypothalamic dysfunction, highlighting the mechanistic aspects related to the anti-inflammatory effects of exercise. In HFD-fed animals, both acute and chronic moderate-intensity exercise mitigate microgliosis and lower inflammation in the arcuate nucleus (ARC). Notably, this associates with restored leptin sensitivity and lower food intake. Exercise-induced cytokines IL-6 and IL-10 mediate part of these positive effect on the ARC in obese animals. The reduction of obesity-associated pro-inflammatory mediators (e.g., FFAs, TNFα, resistin, and AGEs), and the improvement in the gut–brain axis represent alternative paths through which regular exercise can mitigate hypothalamic inflammation. These findings suggest that the regular practice of exercise can restore a proper functionality in the hypothalamus in obesity. Further analysis investigating the crosstalk muscle–hypothalamus would help toward a deeper comprehension of the subject.

Tertiary hyperparathyroidism (HPT III) occurs when an excess of parathyroid hormone (PTH) is secreted by parathyroid glands, usually after longstanding secondary hyperparathyroidism. Some authorities reserve the term for secondary hyperparathyroidism that persists after successful renal transplantation. Long-standing chronic kidney disease (CKD) is associated with several metabolic disturbances that lead to increased secretion of PTH, including hyperphosphatemia, calcit-riol deficiency, and hypocalcaemia. Hyperphosphatemia has a direct stimulatory effect on the parathyroid gland cell resulting in nodular hyperplasia and increased PTH secretion. Prolonged hypocalcaemia also causes parathyroid chief cell hyperplasia and excess PTH. Af-ter correction of the primary disorder CKD by renal transplant, the hypertrophied parathyroid tissue fails to resolute, enlarge over and continues to oversecrete PTH, despite serum calcium levels that are within the reference range or even elevated. They also may become resistant to calcimimetic treatment. The main indication for treatment is persistent hypercalcemia and/or an increased PTH, and the primary treatment is surgery. Three procedures are commonly performed: total parathyroidectomy with or without autotransplantation, subtotal parathyroidectomy, and limited parathyroidectomy. It is important to remove superior parts of thymus as well. The most appropriate surgical procedure, whether it be total, subtotal, or anything less than subtotal including "limited" or "focused" parathyroidectomies, continues to be unclear and controversial. Surgical complications are rare, and para-thyroidectomy appears to be a safe and feasible treatment option for HPT III.

Purpose Fatty acids (FA), particularly polyunsaturated (PUFA) ones, are involved in the regulation of glycemic control, lipid metabolism, and inflammation. The aim of the study was to assess patient FA profile in relation to obesity, lipid and carbohydrate metabolism disturbances, and weight loss. Materials and Methods The studied group consisted of 51 patients with extreme obesity, 23 of whom achieved radical weight reduction within 1 year after a laparoscopic sleeve gastrectomy (LSG). FA levels were determined using gas chromatography with flame ionization detection. Results Patients with extreme obesity and higher serum PUFA content have lower serum levels of SFA and MUFA (especially myristic, palmitic, lignoceric acids and palmitoleic, oleic acids), as well as lower triglyceride and higher HDL-cholesterol concentrations and it was not influenced by CEPT Taq1B variant. At baseline, the fatty acid profile of patients with type II diabetes differ from patients with dyslipidemia. In patients who had lost weight, significantly lower levels of selected saturated FA and major trans-fatty acid, elaidic, were found. Moreover, the proportion of PUFA was increased. Conclusion In extreme obesity, higher PUFA exert their favorable effects on serum lipids. Significant weight reduction after the bariatric surgery is associated with beneficial changes in the fatty acid profile. Graphical Abstract

Scopoletin, a typical example of a coumarin compound, exists in several Artemisia species and other plant genera. However, the systemic metabolic effects induced by scopoletin remain unclear. In the present study, we evaluated the metabolic profiles in scopoletin-exposed zebrafish embryos using UHPLC-Q-Obitrap-HRMS combined with multivariate analysis. Compared with the control group, 33 metabolites in scopoletin group were significantly upregulated, while 27 metabolites were significantly downregulated. Importantly, scopoletin exposure affected metabolites mainly involved in phosphonate and phosphinate metabolism, vitamin B6 metabolism, histidine metabolism, sphingolipid metabolism, and folate biosynthesis. These results suggested that scopoletin exposure to zebrafish embryos exhibited marked metabolic disturbance. This study provides a perspective of metabolic impacts and the underlying mechanism associated with scopoletin exposure.

Successful pregnancy requires adaptation in maternal physiology. During intrauterine life the mother's circadian timing system supports successful birth and postnatal development. Maternal melatonin is important to transmit circadian timing and day length to the fetus. This study aims to describe the third trimester of pregnancy among day (n = 5) and night (n = 3) workers by assessing their melatonin levels in a natural environment. Additionally, we describe the worker's metabolic profiles and compare the health status of the newborns between groups of day and night working mothers. Our results indicate an occurrence of assisted delivery (cesarean and forceps) among night workers. Moreover, the newborns of night workers showed lower Apgar index and breastfeeding difficulty indicating a worse condition to deal with the immediate outside the womb environment. Additionally, there was lower night-time melatonin production among pregnant night workers compared to day workers. These findings may be related to light-induced suppression of melatonin that occurs during night work. We conclude that night work and consequent exposure to light at unconventional times might compromise the success of pregnancy and the health of the newborn. Further studies need to be carried out to monitor pregnancy and newborn health in pregnant night workers., Graphical abstract Image 1, Highlights • There was lower night-time melatonin production among pregnant night workers compared to day workers. • Night work might compromise the success of pregnancy. • Night work during pregnancy might compromise the health of the newborn.

In recent decades a worldwide increase has been reported in the consumption of unhealthy high calorie diets associated with marked changes in meal nutrient composition, such as a higher intake of refined carbohydrates, which leads to the speculatation that changes in food habits have contributed to the current epidemic of obesity and type 2 diabetes. Among these refined carbohydrates, fructose has been deeply investigated and murine models of high fructose diet have emerged as useful tools to study dietary-induced insulin resistance, impaired glucose tolerance, dyslipidemia and alterations in glucose metabolism. Since oxidative stress has been demonstrated to play a key pathogenic role in the alterations described above, several lines of research have focused on the possible preventive effects of antioxidant/ redox state regulation therapy, among which alpha-lipoic acid has been extensively investigated. The following references discussed support the fact that co-administration of alpha-lipoic acid normalized the changes generated by fructose rich diets, thereby making this compound a good therapeutic tool, also administered as a food supplement, to prevent endocrine–metabolic disturbances triggered by high fructose associated with obesity and type 2 diabetes at an early stage of development (prediabetes). Fil: Castro, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Villagarcía, Hernán Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Massa, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina Fil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Endocrinología Experimental y Aplicada; Argentina

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine and metabolic disorder, affecting 5–10% of women of reproductive age. It results from complex environmental factors, genetic predisposition, hyperinsulinemia, hormonal imbalance, neuroendocrine abnormalities, chronic inflammation, and autoimmune disorders. PCOS impacts menstrual regularities, fertility, and dermatological complications, and may induce metabolic disturbances, diabetes, and coronary heart disease. Comprehensive metabolic profiling of patients with PCOS may be a big step in understanding and treating the disease. The study aimed to search for potential differences in metabolites concentrations among women with PCOS according to different body mass index (BMI) in comparison to healthy controls. We used broad-spectrum targeted metabolomics to evaluate metabolites’ serum concentrations in PCOS patients and compared them with healthy controls. The measurements were performed using high-performance liquid chromatography coupled with the triple quadrupole tandem mass spectrometry technique, which has highly selective multiple reaction monitoring modes. The main differences were found in glycerophospholipid concentrations, with no specific tendency to up-or down-regulation. Insulin resistance and elevated body weight influence acylcarnitine C2 levels more than PCOS itself. Sphingomyelin (SM) C18:1 should be more intensively observed and examined in future studies and maybe serve as one of the PCOS biomarkers. No significant correlations were observed between anthropometric and hormonal parameters and metabolome results.

Background Parkinson’s disease (PD) is a prevalent neurological disease in the elderly with increasing morbidity and mortality. Despite enormous efforts, rapid and accurate diagnosis of PD is still compromised. Metabolomics defines the final readout of genome-environment interactions through the analysis of the entire metabolic profile in biological matrices. Recently, unbiased metabolic profiling of human sample has been initiated to identify novel PD metabolic biomarkers and dysfunctional metabolic pathways, however, it remains a challenge to define reliable biomarker(s) for clinical use. Methods We presented a comprehensive metabolic evaluation for identifying crucial metabolic disturbances in PD using liquid chromatography-high resolution mass spectrometry-based metabolomics approach. Plasma samples from 3 independent cohorts (n = 460, 223 PD, 169 healthy controls (HCs) and 68 PD-unrelated neurological disease controls) were collected for the characterization of metabolic changes resulted from PD, antiparkinsonian treatment and potential interferences of other diseases. Unbiased multivariate and univariate analyses were performed to determine the most promising metabolic signatures from all metabolomic datasets. Multiple linear regressions were applied to investigate the associations of metabolites with age, duration time and stage of PD. The combinational biomarker model established by binary logistic regression analysis was validated by 3 cohorts. Results A list of metabolites including amino acids, acylcarnitines, organic acids, steroids, amides, and lipids from human plasma of 3 cohorts were identified. Compared with HC, we observed significant reductions of fatty acids (FFAs) and caffeine metabolites, elevations of bile acids and microbiota-derived deleterious metabolites, and alterations in steroid hormones in drug-naïve PD. Additionally, we found that L-dopa treatment could affect plasma metabolome involved in phenylalanine and tyrosine metabolism and alleviate the elevations of bile acids in PD. Finally, a metabolite panel of 4 biomarker candidates, including FFA 10:0, FFA 12:0, indolelactic acid and phenylacetyl-glutamine was identified based on comprehensive discovery and validation workflow. This panel showed favorable discriminating power for PD. Conclusions This study may help improve our understanding of PD etiopathogenesis and facilitate target screening for therapeutic intervention. The metabolite panel identified in this study may provide novel approach for the clinical diagnosis of PD in the future.

Background: Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, anovulation, infertility, obesity, and insulin resistance, which results in increased concentrations of testosterone (T), which disturbs follicular growth and ovulation. This study aimed to assess PCOS women&rsquo, s clinical, endocrinological, and metabolic parameters concerning hyperandrogenism severity. Results: 314 women (mean age 27.3 &plusmn, 4.6, mean body mass index (BMI) 25.7 &plusmn, 5.6) with PCOS, were divided into terciles according to T concentrations: &lt, 0.64 ng/mL (group 1), 0.64 to 0.84 ng/mL (Group 2) and &gt, 0.84 ng/mL (group 3). The mean concentration of T in all women was 0.59 ng/mL and correlated negatively with the number of menstrual cycles per year (MPY) (r = &minus, 0.36, p &lt, 0.0001) and positively with Ferriman-Gallway score (FG) (r = 0.33, 0.0001), luteinizing hormone (LH) (r = 0.19, 0.0001) and dehydroepiandrosterone sulfate (DHEAS) (r = 0.52, 0.0001). Positive correlation between BMI and hirsutism (r = 0.16, 0.0001), total cholesterol (TC) (r = 0.18, 0.0001), low-density lipoprotein (LDL) (r = 0.29, 0.0001), and triglycerides (TG) (r = 0.40, 0.0001) was demonstrated. The division into subgroups confirmed the lowest MPY, highest LH, and hirsutism in group 3. BMI, insulin sensitivity indices, and lipid profile parameters were not different between the three T subgroups. Conclusions: We found no correlation between testosterone levels and insulin sensitivity or dyslipidemia in women with PCOS. Metabolic abnormalities may contribute more significantly than hyperandrogenemia to PCOS development.

We investigated whether an Information and Communication Technology (ICT) application (app) motivated to increase adherence to lifestyle changes, and to improve indicators of metabolic disturbances among Japanese civil servants. A non-randomized, open-label, parallel-group study was conducted with 102 participants aged 20&ndash, 65 years undergoing a health check during 2016&ndash, 2017, having overweight and/or elevated glucose concentration. Among them, 63 participants chose Specific Health Guidance (SHG) and ongoing support incorporating the use of an app (ICT group) and 39 individuals chose only SHG (control group). Fifty from the ICT group and 38 from the control group completed the study. After completing the 6-month program, the control group showed a significant decrease in body mass index (p = 0.008), male waist circumference (p &lt, 0.001), systolic blood pressure (BP) (p = 0.005), diastolic BP (p &lt, 0.001), and glycated hemoglobin (HbA1c) (p &lt, 0.001), and increase in high-density lipoprotein (HDL) cholesterol (p = 0.008). However, the ICT group showed a significant decrease in male waist circumference (p &lt, 0.001), diastolic BP (p = 0.003), and HbA1c (p &lt, 0.001), and increase in HDL cholesterol (p = 0.032). The magnitude of change for most indicators tended to be highest for ICT participants (used the app &ge, 5 times/month). Both groups reported raised awareness on BP and weight. The app use program did not have a major impact after the observation period. Proper action requires frequent use of the app to enhance best results.

ObjectiveImpaired diabetic wound healing is one of the serious complications associated with diabetes. In patients with diabetes, this impairment is characterized by several physiological abnormalities such as metabolic changes, reduced collagen production, and diminished angiogenesis. We designed and developed a multimodal optical imaging system that can longitudinally monitor formation of new blood vessels, metabolic changes, and collagen deposition in a non-invasive, label-free manner.Research design and methodsThe closure of a skin wound in (db/db) mice, which presents delayed wound healing pathologically similar to conditions in human type 2 diabetes mellitus, was non-invasively followed using the custom-built multimodal microscope. In this microscope, optical coherence tomography angiography was used for studying neovascularization, fluorescence lifetime imaging microscopy for nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) assessment, fluorescence intensity changes of NAD(P)H and flavin adenine dinucleotide (FAD) cofactors for evaluating metabolic changes, and second harmonic generation microscopy for analyzing collagen deposition and organization. The animals were separated into four groups: control, placebo, low concentration (LC), and high concentration (HC) treatment. Images of the wound and surrounding areas were acquired at different time points during a 28-day period.ResultsVarious physiological changes measured using the optical imaging modalities at different phases of wound healing were compared. A statistically significant improvement in the functional relationship between angiogenesis, metabolism, and structural integrity was observed in the HC group.ConclusionsThis study demonstrated the capability of multimodal optical imaging to non-invasively monitor various physiological aspects of the wound healing process, and thus become a promising tool in the development of better diagnostic, treatment, and monitoring strategies for diabetic wound care.

Background: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women at reproductive age, which is characterized by obesity, hyperandrogenemia, and insulin resistance (IR). This study aimed to investigate the vitamin D status, and analyze the relationship between vitamin D deficiency and metabolic risk factors in PCOS women in Shaanxi China.Methods: A cross-sectional study included 169 women diagnosed with PCOS and 114 control women without PCOS. The serum 25(OH)D and metabolic markers were measured. Vitamin D deficiency was defined as serum 25(OH)D concentration less than 20 ng/mL. The primary outcome was the difference in vitamin D status between the PCOS and control groups, the secondary outcomes were correlations between serum 25(OH)D concentration and metabolic risk factors in women with PCOS.Results: The serum 25(OH)D concentration was significantly lower in women with PCOS than in controls (P < 0.05), and the prevalence rates of 25(OH)D deficiency and insufficiency were significantly higher in women with PCOS than in controls (P < 0.05). The serum 25(OH)D concentration was significantly lower in PCOS women with obesity or IR than in women without obesity or IR (P < 0.05), and the prevalence of 25(OH)D deficiency in PCOS women with obesity or IR was significantly higher than in women without obesity or IR (P < 0.05). Serum 25(OH)D concentration was significantly negatively correlated with body mass index (BMI), waist-to-hip ratio (WHR), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP) (P < 0.05). In comparison, serum 25(OH)D concentration was significantly positively correlated with high-density lipoprotein cholesterol (HDL-C) (P < 0.05). Increased BMI and WHR, high levels of fasting insulin, HOMA-IR, total cholesterol, LDL-C and hs-CRP were regarded as risk factors, but high level of HDL-C was considered to be protective factor of vitamin D deficiency in PCOS women.Conclusions: Vitamin D deficiency is prevalent in PCOS women in Shaanxi China, especially in those with obesity and IR. The serum 25(OH)D level was correlated with metabolic risk factors in PCOS women. Multi-center randomized controlled trials with large sample sizes are needed to probe the metabolic effect of vitamin D supplementation in PCOS women.

In recent decades, the prevalence of hyperuricemia (HU) is increasing worldwide; the role of uric acid (UA) in the genesis of various metabolic disorders, cardiovascular diseases, and kidney disease is being discussed. There are very few investigations of the rate of HU and its role in the development of diseases in certain social groups, including in professional athletes.Objective:to estimate the prevalence of HU and its role in the genesis of various pathological conditions and metabolic disturbances in professional athletes.Patients and methods.A retrospective comparative one-stage study was conducted, for which 2148 athletes who met inclusion criteria were selected and examined in the Federal Research and Clinical Center for Sports Medicine and Rehabilitation, Federal Biomedical Agency, in 2015. A control group consisted of 99 ageand sex-matched healthy volunteers examined at the V.A. Nasonova Research Institute of Rheumatology in 2017. The analysis included a comparison of the rate of HU and other examined parameters in professional athletes and healthy volunteers. The examined parameters were separately compared in athletes with/without HU, followed by statistical processing of results.Results.HU was detected in 306 (14.2%) of the 2148 athletes, more often in men (n=253 (20%) than in women (n=53 (6%); (pConclusion.HU is detected quite often in professional athletes (14.2%), which is comparable with the indicators seen in healthy volunteers (12.1%). The high prevalence of HU and its association with indicators reflecting kidney function, lipid metabolic disturbances, and BMI necessitate further investigations aimed at searching the causes of HU and methods of its prevention and treatment in professional athletes.

Mentally disordered offenders provided with forensic psychiatric care are often treated with second generation antipsychotic (SGA) medication and experience metabolic and inflammatory side effects. Aim: In this paper, we monitored the three-year fluctuation of selected anthropometric, biochemical, and inflammatory indices in forensic psychiatric patients receiving antipsychotic (AP) medication for more than five years, according to the type of AP. Methods: Thirty-five patients with psychotic disorders were classified into two groups based on the type of AP. Specifically: AP1, related to a lower risk, and AP2, related to an increased risk of weight gain (WG) and metabolic complications. Biochemical, hematological, anthropometric, blood pressure (BP), and medication data were retrieved from the individual medical files. Statistical analysis was performed with SPSS 23. Results: No significant differences in weight and glucose and cholesterol levels were observed, but patients taking AP2 more often needed drugs to control diabetes mellitus (DM), lipidemia, and cardiovascular disease (CVD). In those taking AP1, the mean HDL level decreased significantly over time (p &lt, 0.05) and a higher proportion developed higher BP (52.9% of AP1 vs. 16.7% AP2). In the AP2 group the median level of C-reactive protein (CRP) (p &lt, 0.001) and the white blood cell count (WBC) increased over the three years (p &lt, 0.001). Conclusions: The proposed sub-classification of SGAs into AP1 and AP2, depending on their potential for metabolic and inflammatory effects, might facilitate study of their long-term side-effects but also help in personalized prevention or treatment measures to counteract these side-effects.

Purpose The purpose of the study was to identify serum microRNAs providing a link between male subfertility and metabolic syndrome (MetS) and validate their diagnostic potential. Methods Sera were analyzed for fertility and MetS-related parameters in subfertile men (n = 79) and controls (n = 38). Literature review identified miR-155-5p, miR-122-5p, miR-200a-3p, and miR-200c-3p which previously were associated with parameters of fertility as well as metabolic disorders. They were measured in the sera using an absolute quantitation method (qPCR). In order to investigate the value of miRNAs in predicting subfertility, receiver operating characteristic analysis was done. Results Subfertile men had higher concentrations of miR-155-5p than controls (p = 0.003) and for miR-200c-3p, the difference was borderline statistically significant (p = 0.05). miR-155-5p and miR-200c-3p were also associated with subfertility in men with no metabolic disturbances (p = 0.008, p = 0.004, respectively). This association was abrogated if any component of MetS was present. The combination of miR-155-5p and miR-200c-3p with follicle-stimulating hormone, being a well-established subfertility parameter, resulted in an overall diagnostic power of AUC = 0.87, which was even higher when men without MetS components were analyzed (AUC = 0.93). Regarding MetS components, statistically significant correlations were found between miR-122-5p and fasting triglycerides, and waist circumference, but no association with subfertility was identified. Conclusions Among the four miRNAs analyzed, none of them was associated both with male subfertility and MetS components. The ability of miR-155-5p and miR-200c-3p to identify subfertile men was partly overruled by the presence of metabolic disturbances. Electronic supplementary material The online version of this article (doi:10.1007/s10815-017-0989-0) contains supplementary material, which is available to authorized users.

Objective To evaluate the anti-obesity activity of bixin (BIX) on C57BL/6J mice which were fed a high-fat diet (HFD) and to determine the mechanism of this effect. Methods C57BL/6J mice were separately fed a high-calorie diet or a normal diet for 8 weeks, then they were treated with BIX for another 13 weeks. After administration for 13 weeks, the animals were sacrificed. Body adiposity, serum lipid level, and insulin resistance were evaluated. In addition, a histological assay of pancreas and liver, an evaluation of the inhibitory properties on pancreatic lipase, and α-amylase were conducted. Results Administration of BIX significantly decreased the body weight gain, adipocyte size, fat pad weights, hepatic lipid levels in HFD-induced obese mice. In addition, reduced liver weight exhibited decreased serum leptin levels, malic enzyme, glucose-6-phosphate dehydrogenase, hepatic fatty acid synthase, aspartate aminotransferase, alanine aminotransferase and hepatic phosphatidate phosphohydrolase activity. However, superoxide dismutase, catalase, glutathione peroxidase, and glutathione levels were increased in hepatic tissue. BIX also decreased lipid and carbohydrates absorption due to inhibition of pancreatic lipase and α-amylase. Long term supplementation of BIX significantly decreased hyperlipidemia, insulin resistance and glucose level. Decreased levels of hepatic steatosis and the islets of Langerhans appeared less shrunken in HFD-fed mice. Conclusions The antiobesity effect of BIX appears to be associated at least in part, to its inhibitory effect on lipids and carbohydrate digestion enzymes such as pancreatic lipase, α-glucosidase, and α-amylase. The results suggested that BIX also act as an antioxidant and may treat visceral obesity normalizing glucose levels, improving insulin resistance and increasing energy expenditure. Therefore, achiote which has a main component, the carotenoid BIX, could be a viable food for the treatment of obesity and diabetes.

Objective: Nonalcoholic fatty liver disease is the commonest diffuse liver disease, of which women with polycystic ovary syndrome are at an increased risk. The aim of the present study was to assess the diagnostic value of the semiquantitative strain parameters of real-time ultrasound elastography for nonalcoholic fatty liver disease in patients with polycystic ovary syndrome. Subjects and methods: Thirty-five polycystic ovary syndrome patients with nonalcoholic fatty liver disease, 70 polycystic ovary syndrome patients without nonalcoholic fatty liver disease, and 70 healthy female controls of reproductive age were included. All participants underwent ultrasonic examination and semiquantitative analysis of real-time ultrasound elastography of the liver. Results: Main semi quantitative strain parameters, such as average strain value, differed significantly among groups polycystic ovary syndrome with nonalcoholic fatty liver disease, polycystic ovary syndrome without nonalcoholic fatty liver disease, and control (87.02 ± 10.16 vs. 96.31 ± 11.44 vs. 104.49 ± 7.28, p < 0.001). Clinical and laboratory parameters differed significantly between the two subgroups with low or high average strain value. For diagnostic value of average strain value for elevated aminotransferase, the area under the curve was 0.808 (range 0.721-0.895). In multiple linear regression analysis, polycystic ovary syndrome, waist circumference, and metabolic syndrome were stand-alone independent factors associated with average strain value among subjects without nonalcoholic fatty liver disease. Conclusion: Semiquantitative real-time ultrasound elastography analysis could distinguish liver parenchyma alterations in patients with polycystic ovary syndrome more sensitively. The diagnostic value of the proposed method for nonalcoholic fatty liver disease need further research.

Isocitrate dehydrogenases (IDH) 1 and 2 are key metabolic enzymes that generate reduced nicotinamide adenine dinucleotide phosphate (NADPH) to maintain a pool of reduced glutathione and peroxiredoxin, and produce α-ketoglutarate, a co-factor of numerous enzymes. IDH1/2 is mutated in ~70–80% of lower-grade gliomas and the majority of secondary glioblastomas. The mutant IDH1 (R132H), in addition to losing its normal catalytic activity, gains the function of producing the d-(R)-2-hydroxyglutarate (2-HG). Overproduction of 2-HG in cancer cells interferes with cellular metabolism and inhibits histone and DNA demethylases, which results in histone and DNA hypermethylation and the blockade of cellular differentiation. We summarize recent findings characterizing molecular mechanisms underlying oncogenic alterations associated with mutated IDH1/2, and their impact on tumor microenvironment and antitumor immunity. Isoform-selective IDH inhibitors which suppress 2-HG production and induce antitumor responses in cells with IDH1 and IDH2 mutations were developed and validated in preclinical settings. Inhibitors of mutated IDH1/2 enzymes entered clinical trials and represent a novel drug class for targeted therapy of gliomas. We describe the development of small-molecule compounds and peptide vaccines targeting IDH-mutant gliomas and the results of their testing in preclinical and clinical studies. All those results support the translational potential of strategies targeting gliomas carrying IDH1 mutations.

Isocitrate dehydrogenases (IDH) 1 and 2 are key metabolic enzymes that generate reduced nicotinamide adenine dinucleotide phosphate (NADPH) to maintain a pool of reduced glutathione and peroxiredoxin, and produce α-ketoglutarate, a co-factor of numerous enzymes. IDH1/2 is mutated in ~70–80% of lower-grade gliomas and the majority of secondary glioblastomas. The mutant IDH1 (R132H), in addition to losing its normal catalytic activity, gains the function of producing the d-(R)-2-hydroxyglutarate (2-HG). Overproduction of 2-HG in cancer cells interferes with cellular metabolism and inhibits histone and DNA demethylases, which results in histone and DNA hypermethylation and the blockade of cellular differentiation. We summarize recent findings characterizing molecular mechanisms underlying oncogenic alterations associated with mutated IDH1/2, and their impact on tumor microenvironment and antitumor immunity. Isoform-selective IDH inhibitors which suppress 2-HG production and induce antitumor responses in cells with IDH1 and IDH2 mutations were developed and validated in preclinical settings. Inhibitors of mutated IDH1/2 enzymes entered clinical trials and represent a novel drug class for targeted therapy of gliomas. We describe the development of small-molecule compounds and peptide vaccines targeting IDH-mutant gliomas and the results of their testing in preclinical and clinical studies. All those results support the translational potential of strategies targeting gliomas carrying IDH1 mutations.

Objective: To explore changes in eating behaviours, inherent weight gain and the metabolic consequences in severely mentally ill patients treated with antipsychotic medications. Method: We conducted a comprehensive review of studies that investigated eating behaviours in mentally ill patients taking antipsychotic treatments. We included records that considered weight change and/or varying degrees of adverse metabolic effects and related metabolic disturbances, such as obesity, dyslipidaemia, type 2 diabetes mellitus, hypertension, metabolic syndrome and cardiovascular diseases. We adopted a systematic approache (PRISMA) and considered 4 electronic databases: PubMed, Medline, Embase, and Psychinfo. Moreover, we conducted a manual synthesis of the bibliographies of the identified articles. Results: We identified 29 full-text human studies that investigated the relationship between antipsychotic drugs and changes in eating behaviours resulting in weight gain and other metabolic complications. Twenty-one of the 29 studies demonstrated the emergence of at least one mechanism of disturbed eating behaviour underlying the weight-promoting effects of antipsychotic medication, whereas six studies reported no impact. Conclusion: Despite the limitations of this review, we can conclude that second-generation antipsychotic (SGA) treatment plays a significant role in the weight gain of patients affected by serious mental disorders because these drugs can lead to abnormal appetite, excessive food intake, and cognitive disinhibition, resulting in high morbidity and mortality. The interest in evaluating eating and feeding behaviours in severely mentally ill patients taking psychotropic drugs is still nascent, and studies in the field are scarce and heterogeneous. Future studies should include long-term, double-blind randomized controlled trials with a large sample size and comparable data for several antipsychotics as well as standardized and validated tools to measure eating behaviours.

International audience; Excessive consumption of industrialized food and beverages is a major etiologic factor in the epidemics of obesity and associated metabolic diseases because these products are rich in fat and sugar. In addition, they contain food contact materials and environmental pollutants identified as metabolism disrupting chemicals. To evaluate the metabolic impact of these dietary threats (individually or combined), we used a male mouse model of chronic exposure to a mixture of low-dose archetypal food-contaminating chemicals that was added in standard or high-fat, high-sucrose (HFHS) diet. Specifically, the mixture contained bisphenol A, diethylhexylphthalate, 2,3,7,8-tetrachlorodibenzo-p-dioxine and polychlorinated biphenyl 153. Exposure lasted from 5 to 20 weeks of age. Metabolic exploration was conducted setting the basis of candidate gene expression mRNA analyses in liver, jejunum and adipose tissue depots from 20 week-old mice. Strong metabolic deleterious effects of the HFHS diet were demonstrated in line with obesity-associated metabolic features and insulin resistance. Pollutant exposure resulted in significant changes on plasma triglyceride levels and on the expression levels of genes mainly encoding xenobiotic processing in jejunum; estrogen receptors, regulators of lipoprotein lipase and inflammatory markers in jejunum and adipose tissues as well as adipogenesis markers. Importantly, the impact of pollutants was principally evidenced under standard diet. In addition, depending on nutritional conditions and on the metabolic tissue considered, the impact of pollutants could mimic or oppose the HFHS effects. Collectively, the present study extends the cocktail effect concept of a low-dosed pollutant mixture and originally points to tissue-specificity responsiveness especially in jejunum and adipose tissues.

International audience; Excessive consumption of industrialized food and beverages is a major etiologic factor in the epidemics of obesity and associated metabolic diseases because these products are rich in fat and sugar. In addition, they contain food contact materials and environmental pollutants identified as metabolism disrupting chemicals. To evaluate the metabolic impact of these dietary threats (individually or combined), we used a male mouse model of chronic exposure to a mixture of low-dose archetypal food-contaminating chemicals that was added in standard or high-fat, high-sucrose (HFHS) diet. Specifically, the mixture contained bisphenol A, diethylhexylphthalate, 2,3,7,8-tetrachlorodibenzo-p-dioxine and polychlorinated biphenyl 153. Exposure lasted from 5 to 20 weeks of age. Metabolic exploration was conducted setting the basis of candidate gene expression mRNA analyses in liver, jejunum and adipose tissue depots from 20 week-old mice. Strong metabolic deleterious effects of the HFHS diet were demonstrated in line with obesity-associated metabolic features and insulin resistance. Pollutant exposure resulted in significant changes on plasma triglyceride levels and on the expression levels of genes mainly encoding xenobiotic processing in jejunum; estrogen receptors, regulators of lipoprotein lipase and inflammatory markers in jejunum and adipose tissues as well as adipogenesis markers. Importantly, the impact of pollutants was principally evidenced under standard diet. In addition, depending on nutritional conditions and on the metabolic tissue considered, the impact of pollutants could mimic or oppose the HFHS effects. Collectively, the present study extends the cocktail effect concept of a low-dosed pollutant mixture and originally points to tissue-specificity responsiveness especially in jejunum and adipose tissues.

Background Neonatal seizures or fits are signs of central nervous system (CNS) diseases, metabolic disorders, or other diseases disrupting the CNS. Neonatal seizures are poorly classified, under-recognized and often difficult to treat. It is important to recognize the type of neonatal seizures that might be the only sign of a CNS disorder. Objective To recognize the type and etiology of neonatal seizures in several hospitals in Jakarta. Methods This was an observational case series study on full-term and preterm infants who had seizures during hospitalization in Cipto Mangunkusumo, Harapan Kita, and Fatmawati Hospitals between January-June 2005. Neonatal seizures were defined as seizures occurring in the first 28 days of life of a term infant or 44 completed weeks of the infant’s conception age of preterm infant. Results There were 40 neonates who born within the study period and had seizures. Girls were outnumbered boys. Most neonates were full-term with birth weight of more than 2500 grams. Analyses were done on 38 neonates with epileptic and non-epileptic seizures, while the other two who had mixed clinical manifestation were not included. Most seizures occurred in the first 3 days of life (23/38). The most common type was focal clonic (12/14) followed by general tonic (11/24) and motor automatism or subtle (10/24). The most common etiology was hypoxic ischemic encephalopathy (HIE) (19/38) followed by metabolic disturbances, mainly hypocalcaemia (11/38). Conclusion Common types of seizures in neonates were focal clonic, general tonic, and motor automatism (subtle). The most common etiology was HIE followed by metabolic disturbances, mainly hypocalcaemia [Paediatr Indones 2006;46:266-270].

Metabolic disturbances are among the most common disorders diagnosed in pediatric patients after anti-cancer therapy (ACT). The aim of our study was to evaluate the prevalence of metabolic disturbances among patients after ACT. The study group comprised 44 patients (31 boys) treated for solid tumors and 31 patients in the control group. Body weight, height, body mass index (BMI) values, lipid parameters are expressed in Standard Deviation Score (SDS), based on centile charts. Indicators of risk to atherosclerosis were calculated. Obesity/overweight was observed in one third of the patients. Hypercholesterolemia occurred in half of them, elevated tryglicerides (TG) SDS in 11, and elevated low-density lipoprotein cholesterol (LDL-C) SDS in nine of the patients. Increased levels of both cholesterol SDS and LDL SDS were found in nine patients and four of them also showed elevated levels of TG SDS. There were significant differences in lipid parameters between the sexes. Risk indicators of lipid disorders defined by statistical distances (&tau, ) were determined for the study group and the control group. The sum of the risk ratios of lipid disorders in the study group was 150 times higher than in the control group. Patients after ACT require special monitoring of lipids profiles and thyroid function as they are at higher risk for dyslipidemia and atherosclerosis than healthy people.

Objective Patients with Turner syndrome (TS) are at increased risk for metabolic disorders. We aimed to delineate the occurrence and evolution of metabolic comorbidities in TS patients and to determine whether these differ in 45,X monosomy and other karyotypes. Methods A longitudinal and cross-sectional retrospective cohort study was conducted in a tertiary pediatric endocrine unit during 1980–2016. Ninety-eight TS patients, 30 with 45,X monosomy were followed from childhood to early adulthood. Outcome measures included weight status, blood pressure (BP), glucose metabolism, and lipid profile. Results Longitudinal analysis showed a significant change in body mass index (BMI) percentiles over time [F(3,115) = 4.8, P = 0.003]. Age was associated with evolution of elevated BP [systolic BP: odds ratio (OR) = 0.91, P = 0.003; diastolic BP: OR = 0.93, P = 0.023], impaired glucose metabolism (HbA1c: OR = 1.08, P = 0.029; impaired glucose tolerance: OR = 1.12, P = 0.029), and abnormal lipid profile (cholesterol: OR = 1.06, P = 0.01; low-density lipoprotein cholesterol: OR = 1.07, P = 0.041; high-density lipoprotein cholesterol: OR = 1.07, P = 0.033). The occurrence of metabolic comorbidities was similar in 45,X monosomy and other karyotypes. Coexistence of multiple metabolic comorbidities was significantly higher in 45,X monosomy [F(1,72) = 4.81, P = 0.032]. BMI percentiles were positively correlated with metabolic comorbidities (occurrence and number) in each patient (r = 0.35, P = 0.002 and r = 0.383, P = 0.001, respectively). Conclusion Our longitudinal study provides unique insights into the evolution of weight gain and metabolic disorders from childhood to early adulthood in TS patients. Since overweight and increasing age aggravate the risk for metabolic comorbidities, careful surveillance is warranted to prevent and control obesity already from childhood. The more prominent clustering of metabolic comorbidities in 45,X monosomy underscores the importance of a more vigorous intervention in this group.

Background Obesity is a debilitating growing condition and represents a challenge for every surgeon. It is associated with the activation of the inflammatory pathway and this may have a negative impact on the natural history of some rheumatic diseases. Bariatric surgery, reducing obesity, could bring to a minor activation of the well-known inflammatory pathway with improvement of these diseases. The aim of this review is to investigate the role of weight loss, achieved through bariatric surgery, in rheumatic diseases. Materials and methods A systematic review of literature was undertaken to evaluate weight loss subsequent to bariatric surgery in obese patients suffering from some rheumatic diseases (Rheumatoid Arthritis, Psoriasis, Psoriatic Arthritis, Fibromyalgia, Osteoarthritis, Systemic Lupus Erythematous). Three major databases (PUBMED, EMBASE and WEB OF SCIENCE) were searched. Results Three-hundred studies were identified. After screening of titles, abstracts and inclusion criteria sixteen articles were included. Of the selected articles, seven were reviews, five were case reports, one was a clinical report, one was a retrospective study, one was a cohort study and one was an author manuscript. Conclusion Weight loss, obtained through bariatric surgery, seems to reduce serum inflammatory markers as a consequence of the inflammatory pathway reduction and this is connected with both the improvement of some rheumatic diseases as well as with the reduction in the use of medicaments (steroids and immunosuppressors).

To investigate the effects of adiponectin and leptin on the development of metabolic disturbances in women with android and gynoid fat distribution.A total of 101 women aged 40 to 65 years were examined. Anthropometric measurements were made; overweight and obese women with a waist/hip (W/H) ratio of less than 0.83 were referred to as a gynoid fat distribution (GFD) group; and those with a W/H ratio of 0.83 or more were to an android fat distribution (AFD) group. The serum concentrations of triglycerides, high-density lipoprotein cholesterol, and glucose were measured; the levels of insulin, leptin, and adiponectin were determined by enzyme immunoassay. Insulin resistance (IR), HOMA IR, and visceral obesity index (VOI) were calculated.With the same excess adipose tissue accumulation, the women with GFD had a less magnitude of hormonal and metabolic disturbances than those with AFD, whose HOMA-IR also pointed to the presence of IR. VOI was insignificantly higher in the women with GFD and 2.4-fold greater than that in normal weight (NW) women. In the women with GFD and AFD, the concentration of leptin was higher than that in the NW women, which was characteristic of obesity, but the concentration of adiponectin proved to be significantly lower in the patients with AFD and to be unchanged in those with GFD as compared with that in the NW women.The women with AFD are typified by a high VOI, hypoadiponectinemia, IR, and metabolic disturbances, which determine a high risk for cardiovascular events and type 2 diabetes mellitus. In the women with GFD, obesity is associated with normal adiponectinemia and a low VOI and, in terms of hormonal and metabolic characteristics, may be characterized as metabolically healthy obesity.Цель исследования. Изучить влияние адипонектина и лептина на развитие метаболических нарушений у женщин с андроидным и гиноидным типами распределения жира. Материалы и методы. Обследовали 101 женщину в возрасте от 40 до 65 лет. Проводили антропометрическое обследование, при отношении окружность талии к окружности бедер (ОТ/ОБ) менее 0,85 женщин с избыточной массой тела и ожирением относили к группе с гиноидным типом распределения жира (ГТРЖ), а при ОТ/ОБ 0,85 и выше - к группе с андроидным типом распределения жира (АТРЖ). В сыворотке крови измеряли концентрации триглицеридов, холестерина липопротеидов высокой плотности, глюкозы; содержание инсулина, лептина и адипонектина определяли методом иммуноферментного анализа. Рассчитывали индексы инсулинорезистентности (ИР) НОМА-IR и висцерального ожирения (ИВО). Результаты. При одинаковой степени накопления избыточной жировой ткани у женщин с ГТРЖ выраженность гормонально-метаболических нарушений меньше, чем у женщин с АТРЖ, у которых индекс НОМА-IR указывал также на наличие ИР. ИВО у женщин с ГТРЖ недостоверно выше, а у женщин с АТРЖ в 2,4 раза выше, чем у женщин с нормальной массой тела (НМТ). Концентрация лептина у женщин с ГТРЖ и АТРЖ выше, чем у женщин с НМТ, что характерно для ожирения, но концентрация адипонектина оказалась достоверно ниже при АТРЖ и не изменилась при ГТРЖ по сравнению с НМТ. Заключение. Для женщин с АТРЖ характерны высокий ИВО, гипоадипонектинемия, ИР и метаболические нарушения, определяющие высокий риск развития сердечно-сосудистых заболеваний и сахарного диабета 2-го типа. У женщин с ГТРЖ ожирение ассоциировано с нормоадипонектинемией и низким ИВО, и по гормонально-метаболическим характеристикам оно может быть охарактеризовано как 'метаболически здоровое' ожирение.

Age-linked metabolic disturbances, such as liver steatosis and insulin resistance, show greater prevalence in men than in women. Thus, our aim was to analyze these sex-related differences in male and female Wistar rats (aged 26 days and 3, 7, and 14 months), and to assess their potential relationship with alterations in the capacity of adipose tissue expansion and the dysregulation of the main adipokines produced by the adipose tissue, leptin and adiponectin. Adiposity related parameters, blood parameters, the expression of genes related to expandability and inflammation (WAT), lipid metabolism (liver), and leptin and insulin signaling (both tissues) were measured. In females, adiposity index and WAT DNA content gradually increased with age, whereas males peaked at 7 months. A similar sex-dependent pattern was observed for leptin expression in WAT, while Mest expression levels decreased with age in males but not in females. Females also showed increased expression of the proliferation marker PCNA in the inguinal WAT compared to males. In males, leptin/adiponectin ratio greatly increased from 7 to 14 months in a more acute manner than in females, along with an increase in HOMA-IR index and hepatic triacylglyceride content, while no changes were observed in females. In liver, 14-month-old males displayed decreased mRNA levels of lnsr, Ampkor2, and Cptla compared with levels at 7 months. Males also showed decreased mRNA levels of Obrb (both tissues), and increased expression levels of Cd68 and Emrl (WAT) with age. In conclusion, females are more protected from age-related metabolic disturbances, such as insulin resistance, hepatic lipid deposition, and WAT inflammation compared to males. This may be related to their greater capacity for WAT expansion reflected by a greater Mest/leptin mRNA ratio and to their ability to maintain adiponectin levels and preserve leptin sensitivity with aging., This work was supported by the EU's 7th Framework Programme FP7 2007-2013, no. 244995 (BIOCLAIMS Project) and the Institute de Salud Carlos III, Centro de Investigacion Biomedica en Red Fisiopatologla de la Obesidad y Nutrition, CIBERohn. Authors belong to the Nutrigenomics-group at UIB, awarded as Group of Excellence of the Autonomous Community of the Balearic Islands (CAIB) and supported by Direccio General d'Universitats, Recerca i Transferencia del Coneixement of Regional Government (CAIB) and FEDER funds (EU). The Laboratory is a member of the European Research Network of Excellence NuGO (The European Nutrigenomics Organization, EU Contract: no. FP6-506360). NS is granted with a Ph.D. fellowship entitled beta para la formacion de personal investigador, co-funded by the Regional Government (Conselleria d'Educacio, Cultura i Universitats, CAIB) and the European Social Fund (FSE).

Aim. To assess the effectiveness of Mildronate in the prevention of arrhythmias during the perioperative period of open cholecystectomy under intravenous multicomponent anesthesia.Material and methods. In total, 69 patients were divided into 3 groups: with concomitant coronary heart disease (CHD), with essential arterial hypertension (EAH), or without concomitant cardiovascular disease (CVD). Each group was divided into a control subgroup (total n=36) receiving conventional treatment and a main subgroup (total n=33) additionally receiving Mildronate (500 mg twice a day intravenously: 24 hour before the operation, during premedication, during early postanesthetic period, and for 2 days after the operation). Arrhythmic episodes were registered at Holter ECG monitoring for 4 days: 24 hours before the operation; 24 hours of the operation; and 48 hours after the operation. The monitoring period was divided into 6 intervals: 1 — preoperation; 2–6 hours before the operation; 3 — anesthesia start; 4 — anesthesia maintenance; 5 — anesthesia finish; and 6 — second day after the operation.Results. Cardiac arrhythmias were registered not only among patients with EAH and CHD, but also with patients without concomitant CVD.Conclusion. Mildronate therapy reduced the number of arrhythmic episodes at different stages of perioperative period, particularly in the anesthesia start, finish, and maintenance periods among patients with CHD and EAH, as well as among CVD-free patients.

This literature preview presents modern evidence on the mechanisms of prothrombotic status development in diabetes mellitus, taking into consideration the association between metabolic disturbances, increased functional platelet activity, and hemocoagulation.

Researches of the last years showed that changes of local immunity at inflammatory diseases of appendages at women, to be exact a condition of a secondary immunodeficiency at the local level, arising against the main pathological process, are a consequence of an immune inflammation, violation of structure and function of cellular membranes because of lipid peroxidation. Research objective was establishment of changes of the metabolic status at an aggravation chronic salpingoophoritis and detection of efficiency of use in «Gepon's» complex pharmacotherapy and «Longidaza's» various medicinal forms. For this purpose under continuous supervision was the 70th women aged from 20 till 35 years with the established diagnosis chronic salpingoophoritis in an aggravation stage. All patients were divided into four groups according to age, minimum satellite, severity of illness and providing treatment. The first experimental group was included 18 patients with chronic adnexitis in the exacerbation phase, where the standard therapy. The second group was included patients (17 women), which put on «Longidaza» in the form of suppositories (1 suppository 3000 per recti 1 times a day for 5 days). In the third group (18 patients), patients received, in addition to a standard treatment regimen «Gepon» (10 mg per 1 times a day for 5 days). The fourth group was included patients (17 women), which put on «Longidaza» injections (1 suppository 3000 intramuscularly 1 time per day for 5 days). As a result of a research efficiency of use of immunocorrective preparations («Gepon» and «Longidaza») at patients chronic salpingoofority in an aggravation stage in correction of metabolic frustration is established. «Longidaza's» use in the form of candles has corrective and normalizing impact on the broken indicators of the metabolic status at patients chronic salpingoophoritis at local level whereas purpose of an injection form of this preparation normalizes parameters of the oxidatic status at system level. Results of a research allow to draw a conclusion that application in complex pharmacotherapy of patients with chronic salpingoophoritis longidaza and gepon in comparison with standard treatment makes more expressed impact on clinical picture of disease and laboratory indicators at system and local levels, thus maximum efficiency possesses a preparation of longidaza in the form of injections.

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and anti-inflammatory properties and is suggested to be a biomarker of metabolic disturbances. The aim of this study was to investigate the effects of alpha-lipoic acid (ALA) on plasma adiponectin and some metabolic risk factors in patients with schizophrenia. The plasma adipokine levels (adiponectin and leptin), routine biochemical and anthropometric parameters, markers of oxidative stress, and the serum phospholipid fatty acid profile in eighteen schizophrenic patients at baseline, in the middle, and at the end of a 3-month long supplementation period with ALA (500 mg daily) were determined. A significant increase in the plasma adiponectin concentrations, as well as a decrease in fasting glucose and aspartate aminotransferase activity (AST), was found. Baseline AST activity was independently correlated with the adiponectin concentrations. Our data show that ALA can improve plasma adiponectin levels and may play a potential role in the treatment of metabolic risk factor in patients with schizophrenia. Future randomized controlled trials are needed to confirm these preliminary investigations.

The paper is focused on hypoxia and cell ischemia as universal pathogenetic mechanisms of disease development, which can be addressed by both etiotropic and pathogenetic therapy. The latter is represented by the so-called metabolic correctors. At present, one of the most widely used metabolic correctors is mildronate. The authors discuss the effectiveness of mildronate in various clinical situations and also present the relevant original findings.

Obesity is recognised as a condition of low-grade chronic inflammation resulting from macrophage infiltration of adipose tissue and activation of inflammatory pathways by oxidative stress mechanisms that lead to the development of insulin resistance. Various natural bioactive compounds (NBCs) with anti-inflammatory and anti-oxidant effects may im- prove adipocyte dysfunction associated with metabolic syndrome. The present review focuses on the effects of phenolic compounds, n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and lipoic acid (LA) on the pathophysiological mechanisms of obesity. In this review, a total of 120 studies were included, and data thus obtained reflect beneficial physiological effects of n-3 LC-PUFA, LA and different phenolic compounds, including kaempferol, luteolin, apigenin, quercetin, resveratrol, curcumin, catechins, phenolic acids, in the prevention and/or attenuation of metabolic disturbances associated with obesity. Additionally, information from clinical studies provides new insights for defining the dose- response relationship of dietary compounds, necessary time of exposure and potential side effects of these NBCs in the treatment of obesity and indicates further study is needed to verify these relationships.

Recently, more and more attention has been paid to metabolic risk factors (RFs), due to their prognostic importance in the development of cardiovascular disease (CVD) and Type 2 diabetes mellitus. The metabolic effects of antihypertensive medications are actively discussed in the literature. It has been demonstrated that ACE inhibitors, calcium antagonists, and I1-imidasoline receptor agonists (IRA) do not affect metabolic RFs, while diuretics (D) and beta-adrenoblockers could worsen the prognosis. In the new European guidelines, alpha-adrenoblockers and IRA are not regarded as first-choice medications, due to the lacking evidence of their effects on end-points. The paper analyses in detail the results of large-scale international trials on D. In particular, the authors discuss the potential of low-dose thiazide D, as a part of combined therapy, in patients with metabolic disturbances and high cardiovascular risk.

CONTEXTO: Após cinco décadas de síntese e disseminação de uso de drogas para o tratamento da esquizofrenia, foi possível observar a disponibilidade de drogas com diferentes perfis farmacológicos e um largo perfil de efeitos adversos que se estendem além dos originalmente descritos em área endocrinológica e neurológica, se expandindo para aumento de peso, transtornos metabólicos, transtornos cardiovasculares e morte prematura associada a doenças comuns. Estas evidências, agravadas com a relativa ausência de diretrizes e orientações para o clínico, apontam para a necessidade de se produzir orientações claras e sintéticas para uso pelo clínico, orientando para a seleção de drogas e medidas de prevenção e tratamento de transtornos de peso e metabolismo. OBJETIVO: Identificar a freqüência e o tipo de alterações de peso e metabolismo em pessoas diagnosticadas com esquizofrenia, antes e depois do uso de diferentes antipsicóticos, e sintetizar as medidas preventivas e paliativas adequadas para a redução desses desfechos desfavoráveis. MÉTODOS: Efetuada breve revisão em PubMed e Scielo nos últimos cinco anos com os descritores weight, metabolic syndrome AND schizophrenia, e a partir dos artigos encontrados, selecionados artigos com dados clínicos. RESULTADO: Foram identificados aumento de peso, dislipidemia e síndrome metabólica em pacientes portadores do diagnóstico de esquizofrenia, antes, durante e após o uso de antipsicóticos, especialmente em drogas de nova geração, com taxas perto de duas vezes maiores do que na população geral, que resultam de redução de cerca de 20% na expectativa de vida desses pacientes. CONCLUSÃO: Devido a estes riscos elevados e à inexistência de critérios claros de definição de risco de ganho de peso antes da exposição a antipsicóticos (apesar do maior risco associado a uso de clozapina e olanzapina), recomenda-se seguimento ativo de pacientes em regime de drogas antipsicóticas, com troca logo que observado aumento em 5% ou mais no peso corporal, com manutenção do cuidado ativo, com orientação nutricional e de estilo de vida e nível de atividade. Adicionalmente, existe a necessidade de revisões sistemáticas para controlar possíveis vieses de seleção com o tipo de metodologia empregada.BACKGROUND: Five decades after use and dissemination of use of drugs for the treatment of schizophrenia, with different pharmacologic profiles, it has been evidenced that these drugs display a large profile of adverse events other than endocrinological and neurological, including weight gain, metabolic disorders, increased frequency of cardiovascular disorders and premature death associated to common disorders. These evidences, aggravated by the lack of synthetic and clear description of guidelines for the clinical practitioner, points to the need of comprehensive studies about weight gain and metabolic disturbances followed by clear and simple guidelines orienting drug selection and measures for prevention and treatment of weight and metabolic disturbances. OBJECTIVE: Identification of frequency and type of weight and metabolic disturbances in people diagnosed with schizophrenia, before and after the use of different antipsychotics. METHODS: A PubMed and Scielo review of the last 5 years using descriptors such as weight, metabolic syndrome AND schizophrenia, and after that, the authors selected articles with clinical data. RESULT: Increased weight, dislipidemia and metabolic syndrome in subjects with schizophrenia, before, was evidenced during and after drug use, especially new-generation drugs, with overall rates around 2 times the general population, resulting in a 20% reduction of life expectancy in these patients. CONCLUSION: The evidence of elevated risk for overweight and metabolic syndrome and the lack of defined criteria for risk assessment for weight gain before drug use (despite of increased pre-drug use risk with clozapine and olanzapine) it is recommended active follow-up of patients under antipsychotic drug use, with drug change when observed 5% or more weight gain, with maintenance of active care of nutritional, lifestyle and activity level. There is also a need of systematic reviews for controlling selection biases associated to the type of methodology of the present review.

Aim. To assess efficacy of various pharmacotherapy schemes in arterial hypertension (AH) with metabolic disturbances (MD). Material and methods. Open, randomized, comparative study in 3 parallel groups, including 90 patients with Stage I-II AH and MD, was performed. Group 1 was administered moxonidine and eprosartan; Groups 2 and 3 – standard monotherapy (diuretic, beta blocker, calcium antagonist, plus ACE inhibitor in case of low effectiveness); Group 3 additionally received a lipase inhibitor orlistat. Results. Eight weeks later, target BP level was achieved in 86% patients from Group 1, 73% – from Group 2, and 57% - from Group 3. In Group 3, body mass index decreased by 5.3%, and waist circumference – by 3.5%. Total cholesterol level reduced in Groups 1 (by 7.3%) and 3 (by 9.6%). In Group 1, basal immunoactive insulin level declined by 25.2%. Fasting glycemia reduced in Groups 1 and 3 – by 6.3% and 8.6%, respectively. In Group 1, basal cortisol level decreased by 26.3%. All medications were well tolerated. Conclusion. Imidazoline receptor antagonist was more effective than standard therapy: despite compatible antihypertensive effects, moxonidine improved metabolic parameters. Adding orlistat to antihypertensive treatment improved metabolic parameters and 24-hour BP profile in patients with AH and MS.

OBJETIVO: Este trabalho visou estimar as prevalências de excesso de peso e descrever algumas variáveis antropométricas relativas à distribuição da gordura corporal de uma população migrante de origem japonesa residente no Brasil. MÉTODO: A amostra foi constituída por 647 nipo-brasileiros de 1ª (n = 237) e 2ª geração (n = 410), de ambos os sexos, com idade > 35 anos, submetidos a medidas antropométricas, de pressão arterial, perfil lipídico e teste oral de tolerância à glicose. Sobrepeso e obesidade foram diagnosticados por meio de índice de massa corporal (IMC) entre 25-29,9 e > 30 kg/m², respectivamente. O diagnóstico de adiposidade abdominal foi baseado nos valores de circunferência de cintura > 94 cm para homens e > 80 cm para mulheres. Para a análise dos dados foram usados a estatística qui-quadrado e o teste t de Student. RESULTADOS: Dos indivíduos estudados, 40% apresentavam algum grau de excesso de peso (IMC > 25 kg/m²), sendo a prevalência de obesidade abdominal de 21,5% entre os homens e de 66,7% entre as mulheres. Homens nipo-brasileiros < 60 anos de 2ª geração enquadraram-se no perfil andróide de distribuição da gordura corporal; as mulheres mostraram-se mais obesas que os homens, apresentando tanto o padrão andróide como ginóide, avaliado por meio das dobras cutâneas. CONCLUSÃO: Os imigrantes japoneses que originalmente não apresentavam o fenótipo de obesidade acompanharam a tendência mundial atual de ganho progressivo de peso até a obesidade. Em particular, essa situação foi acompanhada de aumento de adiposidade abdominal, possivelmente indicativa de acúmulo de gordura visceral e desencadeante de alterações metabólicas. Estes achados sugerem que indivíduos de origem japonesa devem apresentar uma predisposição à obesidade abdominal, que se manifesta quando expostos a ambiente desfavorável.OBJECTIVE: This study aimed to estimate the prevalence of overweight and to describe some indicative anthropometric variables of body fat distribution in a population of Japanese migrants living in Brazil. METHODS: The sample consisted of 647 first- (n= 237) and second-generation (n= 410) Japanese-Brazilians of both genders, aged > 35 years, who had their anthropometric measures, blood pressure, lipid profile, and oral glucose tolerance test defined. Overweight and obesity were defined as a body mass index (BMI) of 25.0-29.9 and > 30.0 kg/m², respectively; the diagnosis of abdominal adiposity was based on waist circumference values > 94 cm in men and > 80 cm in women. Chi-square statistics and Student t test were used for data analysis. RESULTS: Forty percent of the participants showed some degree of overweight (BMI > 25 kg/m²) and the prevalence rates of abdominal adiposity were 21.5% in men and 66.7% in women. Second-generation Japanese-Brazilian men, younger than 60 years, had an android profile of fat distribution; women were more obese than men and had both android and gynaecoid patterns, which were assessed by skin fold thickness. CONCLUSION: Japanese immigrants in Brazil - who originally did not present the obese phenotype - have followed the worldwide trend of progressive weight gain toward the development of obesity. In particular, such situation has been accompanied by an increase in abdominal adiposity, possibly indicating visceral fat accumulation, triggering metabolic disorders. Our findings suggest that Japanese descendants may present predisposition to abdominal obesity, which is triggered when they are exposed to an unfavorable environment.

Se determinó las variaciones en indicadores sanguíneos y productivos y la presentación de resistencia a insulina y cetosis en vacas lecheras a pastoreo durante los períodos de transición y lactancia temprana que presentaban alta o moderada condición corporal (CC) en el período preparto. El estudio se realizó durante el período de transición (tres semanas [sem] antes y después del parto) y lactancia temprana (cuarta a octava sem posparto). Los grupos se asignaron según CC preparto (escala 1-5): alta ( 3,75; n=20) y moderada (3,00-3,50; n=28). Se evaluaron las variaciones semanales de la CC, peso vivo, producción láctea e indicadores sanguíneos: ácidos grasos no esterificados [NEFA], -hidroxibutirato, glucosa, colesterol, urea, albúmina, aspartato aminotransferasa y glutamato deshidrogenasa. Fue realizada una prueba de tolerancia a glucosa y resistencia a la insulina en nueve vacas posparto de cada grupo. En el preparto se observó una mayor concentración sanguínea de lípidos y glucosa en vacas con alta CC. En las primeras tres sem posparto, las vacas con alta CC produjeron más leche asociado a la mayor glucemia, disminuyendo marcadamente la CC en relación al grupo con moderada CC. En la lactancia temprana se observó mayor glucemia y colesterolemia en las vacas con alta CC. La presentación de resistencia a insulina, balance energético negativo y cetosis fue similar entre los grupos, sin embargo, la excesiva lipomovilización (NEFA>0,40 mmol/L) y la hiperglucemia preparto (>4,1mmol/L) fueron los principales factores de riesgo para la resistencia a insulina en el período de transición. La hiperglucemia preparto también disminuyó el riesgo de balance energético negativo en lactancia temprana. Se concluyó que vacas lecheras a pastoreo con alta CC preparto, presentan mayor movilización de lípidos y glucemia superior durante el período de transición. La presentación de cetosis y resistencia insulínica en vacas lecheras a pastoreo se presenta independiente de la CC preparto, a su vez, dependiente de la cantidad de lípidos movilizados desde el tejido adiposo para soportar la demanda energética de las vacas lecheras. Blood markers for energy balance and milk production values, together with presentation of insulin resistance and ketosis were determined in grazing dairy cows during the periods of transition and early lactation and grouped according with their body condition score (BCS) before calving. The study was done in an experimental dairy herd, during the transitional period (3 weeks before to 3 weeks postcalving and early lactation, 4th to 8th weeks postcalving. Cows were distributed in two groups according to BCS (1 to 5 scale), high ( 3.75; n=20) and moderate (3.00-3.50; n=28). Weekly variations of BCS, live body weight and blood markers for energy (non esterified fatty acids [NEFA], -OH-butyrate, glucose, cholesterol), protein (urea, albumin) and liver damage were determined. A glucose tolerance test and insulin resistance test were carry out during postcalving in nine cows of each group. Cows with high BCS at partum, compared to cows with moderate BCS at partum, had a larger blood lipid and glucose concentrations during precalving, produced more milk during the first three weeks postcalving and their blood glucose and cholesterol values at early lactation were higher, and also had a larger decrease in BCS. Presentation of negative energy balance and ketosis were similar in both groups of cows. However, excessive lipid mobilization (NEFA>0.40 mmol/L) and hyperglycaemia (>4.1 mmol/L) during precalving were the main risk factors for insulin resistance during the transition period. On the other hand hyperglycaemia precalving decreased the risk of a negative energy balance during lactation. It is concluded that dairy cows at pasture with high BCS precalving presents more lipid mobilization and have a higher glycaemia during the transitional period. Ketosis and insulin resistance presentations are independent of the BCS at calving, but are related to the lipid mobilization from the body fat stores to compensate the large demands for energy during lactation. 73 - 82 mirelanoro@gmail.com

Antipsychotics are widely used psychoactive drugs for the treatment of schizophrenia symptoms. The use of second-generation agents has reduced the onset of extrapyramidal disorders, but still causes side effects comprising weight gain, dyslipidemia, and type-2 diabetes. The ensuing deterioration of patients’ conditions is one of the main reasons for the abandonment of this treatment exposing patients to an increased risk of relapse. This PhD had two objectives: (i) to characterize the metabolic disorders generated by a long-term treatment with risperidone, through the use of non-invasive techniques of magnetic resonance (MR); (ii) to prevent these disorders by means of a curcuminoid-supplemented diet. Our murine model enabled us to show that a 24-week treatment including weekly given risperidone induced metabolic disturbances related to the Metabolic Syndrome. Magnetic resonance imaging was sensitive enough to highlight these disturbances and to allow the identification of predictive biomarkers for severity such as the hydrolipidic ratio, fatty acid unsaturation rate, and adipose tissues repartitioning. At the pharmacological level, curcuminoid supplementation prevented the risperidone-induced hepatomegaly and glucose intolerance. These benefits were associated with the modulation of gene expression related to lipogenesis (FAS, ACC1), lipolysis (ACO) or inflammation (NFκB). In a clinical perspective, the herein PhD underlines the diagnostic potential of this MR-based experimental framework for the monitoring of metabolic disturbances., Les antipsychotiques sont des agents psychoactifs utilisés pour traiter les symptômes de la schizophrénie. Si la mise sur le marché de la seconde génération de molécule a permis de diminuer l’apparition des troubles extrapyramidaux, elle reste néanmoins associée à des effets secondaires caractérisés principalement par une prise de poids assortie d’une dyslipidémie et d'un développement du diabète de type 2. Ces effets indésirables entraînent chez les patients une dégradation de leurs conditions de vie et constituent l'une des principales causes d'abandon de ce traitement, les exposant à un risque accru de rechute. L’objectif de ce travail était double : (i) caractériser les troubles métaboliques induits par un traitement à long terme à la rispéridone en utilisant des techniques non-invasives de résonance magnétique ; (ii) prévenir ces troubles par un régime alimentaire supplémenté en curcuminoïdes. Notre modèle a permis de montrer qu'un traitement hebdomadaire de 24 semaines entraînait des perturbations apparentées au syndrome métabolique. L’imagerie par résonance magnétique était suffisamment sensible pour caractériser ces conséquences métaboliques iatrogènes et permettait de définir des biomarqueurs prédictifs de sévérité comme le ratio hydro-lipidique, le degré d’insaturation des acides gras et le remodelage de la répartition des tissus adipeux. Sur le plan pharmacologique, la supplémentation en curcuminoïdes permettait de prévenir l’hépatomégalie et l’intolérance au glucose induite par la rispéridone. Ces bénéfices étaient associés à une modulation de l’expression de gènes hépatiques impliqués dans la lipogenèse (FAS, ACC1), dans la lipolyse (ACO) ou bien dans l’inflammation (NFκB). Le cadre expérimental défini dans ce travail met en avant la possibilité de transférer cette approche prédictive par résonance magnétique en clinique humaine.

Erythrocyte transketolase activity and guanidino compounds in hemodialysis patientsBackgroundThe toxic effects of guanidino compounds on enzymatic activity in uremic patients are known. Thus, we determined the hemodialysis (HD) impact on this toxicity.MethodsThe erythrocyte transketolase activity (ETAK), total guanidino compounds (TGCs), and guanidinosuccnic acid (GSA) levels in plasma were compared before, after 5 hours of HD, and at 12 and 24 hours from the end of HD. Thirty-seven HD patients (28 to 49 years old) with primary glomerulopathies participated in this study. Thirty healthy volunteers (HVs) served as controls.ResultsAt the beginning of this study, ETKA was in uremics (1.94 ± 0.45) than in HVs (2.59 ± 0.26). The TGC and GSA plasma levels were higher (26.07 ± 5.34 and 4.5 ± 1.22) than in HVs (10.41 ± 1.42 and 0.76 ± 0.09,P < 0.001), respectively. After five hours of HD, the ETKA increased to 2.49 ± 2.02 (P < 0.001). The plasma levels TGC decreasd to 12.56 ± 2.02 (P < 0.001) and the GSA to 2.12 ± 0.68 (P < 0.001). After 12 and 24 hours from the end of HD, the ETKA decreased to 2.25 ± 0.56 and 2.09 ± 0.49 (P 0.001), respectively. The plasma levels for TGC and GSA both increased: TGC to 19.39 ± 3.67 and 25.68 ± 4.61 (P < 0.001), respctively; GSA to 3.49 ± 1.11 and 4.53 ± 1.12 (P < 0.001), respectively.ConclusionThere was no significant correlation between ETKA and the plasma levels of the examined toxins. By removing the guanidino compounds, HD temporarily decreases the inhibition of EKTA, diminishing other metabolic disturbances connected with pentose phosphate cycle.

AIM: To test differences in metabolic characteristics among overweight and normally weighted prehypertensives. DESIGN AND METHODS: Out of 2489 subjects enrolled in Croatian rural study, 117 prehypertensives(53 women, 64 men) were included in this analysis. All subjects had blood pressure (BP)and heart rate(HR) measured following the ESH guidelines. BMI and waist circumference(WC) were determined. Fasting blood was analysed for glucose(FBG), insulin, total cholesterol(T-C), HDL, LDL, triglycerides(TG), serum creatinine, haematocrite(Hct), C reactive protein(CRP) and white blood cell count(WBC). HOMA index was used to calculate insulin resistance and MDRD formula to estimate glomerular filtration rate (eGFR). Albumin to creatinine ratio(ACR) and alpha1 microglobin to creatinine ratio(alpha1CR) were determined. Subjects were divided in two groups: group 1: (BMI=25 and WC>=92, N=64). RESULTS: The two groups didn't differ significantly neither in age, in BP nor in HR values (p>0.05). Furthermore, no difference was found in inflammatory markers such as CRP and WBC (p>0.05), but interestingly we found significant difference in hematocrite (0.38 vs 0.40, p=0.0036). Two groups didn't differ in renal function parameters (p>0.05). Finally, we found group 2 to be significantly dislipidemic than group 1, to have higher FBG, insulin and HOMA values (Table 1). CONCLUSION: Significant differences in majority of the cardiovascular risk factors were observed between the overweight and normaly weighted prehypertensives. Drug treatment of prehypertension is still being debated. Higher cardiovascular risk factors in overweight, (but yet not obese) prehypertensive subjects may point out on the target group for potential drug treatment.

Quarenta e cinco RN que apresentaram a síndrome da hiperexcitabilidade, após 72 horas de vida, constituiram o grupo de estudo. Distúrbios metabólicos foram identificados em 53% dos casos, sendo a hipocalcemia o mais freqüente. A anoxia neonatal ocorreu em 21 casos (46%), apesar de todos terem apresentado notas na escala de Apgar acima de 6, no 5º minuto. Apenas 6 casos apresentaram associação de anoxiia neonatal e distúrbios metabólicos. A correção dos distúrbios metabólicos levou ao desaparecimento dos sintomas em apenas 1/3 das crianças. Forty-five newborn infants with hyperexcitability lasting more than 72 hours were studied in the neonatal period. The association with metabolic disturbances, mainly hypocalcemia, was observed in 53% of cases. Neonatal asphyxia was observed in 21 cases (46%), although all infants had 5 minutes Apgar scores above 6. Only 6 cases had association between neonatal asphyxia and metabolic disturbances. The hyperexcitability syndrome faded away in 1/3 of the infants with metabolic abnormalities after their correction.