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OBJECTIVE: Obesity represents a significant global health challenge characterized by chronic low-grade inflammation and metabolic dysregulation. The hypothalamus, a key regulator of energy homeostasis, is particularly susceptible to obesity's deleterious effects. This study investigated the role of the immunoproteasome, a specialized proteasomal complex implicated in inflammation and cellular homeostasis, during metabolic diseases. METHODS: The levels of the immunoproteasome ß5i subunit were analyzed by immunostaining, western blotting, and proteasome activity assay in mice fed with either a high-fat diet (HFD) or a regular diet (CHOW). We also characterized the impact of autophagy inhibition on the levels of the immunoproteasome ß5i subunit and the activation of the AKT pathway. Finally, through confocal microscopy, we analyzed the contribution of ß5i subunit inhibition on mitochondrial function by flow cytometry and mitophagy assay. RESULTS: Using an HFD-fed obese mouse model, we found increased immunoproteasome levels in hypothalamic POMC neurons. Furthermore, we observed that palmitic acid (PA), a major component of saturated fats found in HFD, increased the levels of the ß5i subunit of the immunoproteasome in hypothalamic neuronal cells. Notably, the increase in immunoproteasome expression was associated with decreased autophagy, a critical cellular process in maintaining homeostasis and suppressing inflammation. Functionally, PA disrupted the insulin-glucose axis, leading to reduced AKT phosphorylation and increased intracellular glucose levels in response to insulin due to the upregulation of the immunoproteasome. Mechanistically, we identified that the protein PTEN, a key regulator of insulin signaling, was reduced in an immunoproteasome-dependent manner. To further investigate the potential therapeutic implications of these findings, we used ONX-0914, a specific immunoproteasome inhibitor. We demonstrated that this inhibitor prevents PA-induced insulin-glucose axis imbalance. Given the interplay between mitochondrial dysfunction and metabolic disturbances, we explored the impact of ONX-0914 on mitochondrial function. Notably, ONX-0914 preserved mitochondrial membrane potential and attenuated mitochondrial ROS production in the presence of PA. Moreover, we found that ONX-0914 reduced mitophagy in the presence of PA. CONCLUSIONS: Our findings strongly support the pathogenic involvement of the immunoproteasome in hypothalamic neurons in the context of HFD-induced obesity and metabolic disturbances. Targeting the immunoproteasome highlights a promising therapeutic strategy to mitigate the detrimental effects of obesity on the insulin-glucose axis and cellular homeostasis. This study provides valuable insights into the mechanisms driving obesity-related metabolic diseases and offers potential avenues for developing novel therapeutic interventions.
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Dieta Hiperlipídica , Hipotálamo , Camundongos Endogâmicos C57BL , Neurônios , Obesidade , Complexo de Endopeptidases do Proteassoma , Animais , Dieta Hiperlipídica/efeitos adversos , Camundongos , Hipotálamo/metabolismo , Obesidade/metabolismo , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Masculino , Doenças Metabólicas/metabolismo , Doenças Metabólicas/etiologia , OligopeptídeosRESUMO
AIMS: The aim of this study was to characterize the metabolites associated with small- and large-gestational-age newborns in maternal and cord blood, and to investigate potential mechanisms underlying the association between birthweight and metabolic disturbances. RESEARCH DESIGN AND METHODS: We recorded detailed anthropometric data of mother-offspring dyads. Untargeted metabolomic assays were performed on 67 pairs of cord blood and maternal fasting plasma samples including 16 pairs of small-for-gestational (SGA, < 10th percentile) dyads, 28 pairs of appropriate-for-gestational (AGA, approximate 50 percentile) dyads, and 23 pairs of large-for-gestational (LGA, > 90th percentile) dyads. The association of metabolites with newborn birthweight was conducted to screen for metabolites with U-shaped and line-shaped distributions. The association of metabolites with maternal and fetal phenotypes was also performed. RESULTS: We found 2 types of metabolites that changed in different patterns according to newborn birthweight. One type of metabolite exhibited a "U-shaped" trend of abundance fluctuation in the SGA-AGA-LGA groups. The results demonstrated that cuminaldehyde level was lower in the SGA and LGA groups, and its abundance in cord blood was negatively correlated with maternal BMI (r = -0.352 p = 0.009) and weight gain (r = -0.267 p = 0.043). 2-Methoxy-estradiol-17b 3-glucuronide, which showed enrichment in the SGA and LGA groups, was positively correlated with homocysteine (r = 0.44, p < 0.001) and free fatty acid (r = 0.42, p < 0.001) in maternal blood. Serotonin and 13(S)-HODE were the second type of metabolites, denoted as "line-shaped", which both showed increasing trends in the SGA-AGA-LGA groups in both maternal and cord blood and were both significantly positively correlated with maternal BMI before pregnancy. Moreover, cuminaldehyde, serotonin, 13(S)-HODE and some lipid metabolites showed a strong correlation between maternal and cord blood. CONCLUSIONS: These investigations demonstrate broad-scale metabolomic differences associated with newborn birthweight in both pregnant women and their newborns. The U-shaped metabolites associated with both the SGA and LGA groups might explain the U-shaped association between birthweight and metabolic dysregulation. The line-shaped metabolites might participate in intrauterine growth regulation. These observations might help to provide new insights into the insulin resistance and the risk of metabolic disturbance of SGA and LGA babies in adulthood and might identify potential new markers for adverse newborn outcomes in pregnant women.
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Recém-Nascido Pequeno para a Idade Gestacional , Serotonina , Gravidez , Humanos , Feminino , Recém-Nascido , Peso ao Nascer/fisiologia , Idade GestacionalRESUMO
BACKGROUND: To distinguish the metabolic profile between women with diminished ovarian reserve (DOR) and those with normal ovarian reserve (NOR). METHODS: In this retrospective study, we enrolled 524 women under the age of 40 who were experiencing infertility: 261 in the DOR group and 263 in the NOR group. Physical characteristics and metabolic parameters were compared between these two groups. RESULTS: Women with DOR exhibited a higher propensity for elevated parameters including body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), as well as heightened serum levels of homocysteine (Hcy), triglycerides (TG), low-density lipoprotein (LDL), and triglyceride-glucose (TyG) index, while concurrently experiencing reduced serum levels of high-density lipoprotein (HDL) (P < 0.05). Furthermore, the incidence rates of TG ≥ 1.7 mmol/L, hyperhomocysteinemia (HHcy), BMI ≥ 25 kg/m2, SBP/DBP ≥ 130/85 mmHg, and metabolic syndrome (MS) were significantly elevated within the DOR group as compared to the NOR group (P < 0.05). CONCLUSION: The prevalence of metabolic disturbances and HHcy were notably elevated in women with infertility and DOR compared to those with NOR.
This study focused on the metabolic condition of women who had difficulty getting pregnant and had a decreased ovarian reserve. The findings indicated that these women had a higher likelihood of glucose and lipid metabolic disorders and elevated serum homocysteine levels compared to those with a normal ovarian reserve. These metabolic issues and elevated serum homocysteine levels were associated with an increased risk of cardiovascular disease.
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Hiper-Homocisteinemia , Infertilidade , Síndrome Metabólica , Doenças Ovarianas , Reserva Ovariana , Humanos , Feminino , Estudos Retrospectivos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/epidemiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , TriglicerídeosRESUMO
BACKGROUND: The metabolic defect in glycogen storage disease type I (GSDI) results in fasting hypoglycemia and typical secondary metabolic abnormalities (eg, hypertriglyceridemia, hyperlactatemia, hyperuricemia). The aim of this study was to assess further perturbations of the metabolic network in GSDI patients under ongoing treatment. METHODS: In this prospective observational study, plasma samples of 14 adult patients (11 GSDIa, 3 GSDIb. Mean age 26.4 years, range 16-46 years) on standard treatment were compared to a cohort of 31 healthy controls utilizing ultra-high performance liquid chromatography (UHPLC) in combination with high resolution tandem mass spectrometry (HR-MS/MS) and subsequent statistical multivariate analysis. In addition, plasma fatty acid profiling was performed by GC/EI-MS. RESULTS: The metabolomic profile showed alterations of metabolites in different areas of the metabolic network in both GSD subtypes, including pathways of fuel metabolism and energy generation, lipids and fatty acids, amino acid and methyl-group metabolism, the urea cycle, and purine/pyrimidine metabolism. These alterations were present despite adequate dietary treatment, did not correlate with plasma triglycerides or lactate, both parameters typically used to assess the quality of metabolic control in clinical practice, and were not related to the presence or absence of complications (ie, nephropathy or liver adenomas). CONCLUSION: The metabolic defect of GSDI has profound effects on a variety of metabolic pathways in addition to the known typical abnormalities. These alterations are present despite optimized dietary treatment, which may contribute to the risk of developing long-term complications, an inherent problem of GSDI which appears to be only partly modified by current therapy.
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Doença de Depósito de Glicogênio Tipo I , Hipoglicemia , Adolescente , Adulto , Cromatografia Líquida de Alta Pressão , Doença de Depósito de Glicogênio Tipo I/complicações , Humanos , Hipoglicemia/complicações , Metabolômica , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem , Adulto JovemRESUMO
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.
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Ácidos Graxos Ômega-3 , Síndrome Metabólica , Microalgas , Animais , Dieta Hiperlipídica/efeitos adversos , Ácidos Graxos , Ácidos Graxos Ômega-3/farmacologia , Frutose , Glucose , Insulina , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/prevenção & controle , Obesidade/metabolismo , Ratos , Ratos Wistar , TriglicerídeosRESUMO
Osteoarthritis (OA) and Obstructive Sleep Apnea (OSA) are two highly prevalent chronic diseases for which effective therapies are urgently needed. Recent epidemiologic studies, although scarce, suggest that the concomitant occurrence of OA and OSA is associated with more severe manifestations of both diseases. Moreover, OA and OSA share risk factors, such as aging and metabolic disturbances, and co-morbidities, including cardiovascular and metabolic diseases, sleep deprivation and depression. Whether this coincidental occurrence is fortuitous or involves cause-effect relationships is unknown. This review aims at collating and integrating present knowledge on both diseases by providing a brief overview of their epidemiology and pathophysiology, analyzing current evidences relating OA and OSA and discussing potential common mechanisms by which they can aggravate each other. Such mechanisms constitute potential therapeutic targets whose pharmacological modulation may provide more efficient ways of reducing the consequences of OA and OSA and, thus, lessen the huge individual and social burden that they impose.
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Osteoartrite/epidemiologia , Apneia Obstrutiva do Sono/epidemiologia , Envelhecimento , Animais , Comorbidade , Humanos , Osteoartrite/tratamento farmacológico , Fatores de Risco , Apneia Obstrutiva do Sono/tratamento farmacológicoRESUMO
Introduction: Alzheimer's disease is primarily a dementia-related disorder from progressive cognitive deterioration and memory impairment, while Parkinson's disease is primarily a movement disorder illness having movement disorder symptoms, bradykinesia (slowness of movements), hypokinesia (reduction of movement amplitude), and akinesia (absence of normal unconscious movements) along with muscle rigidity and tremor at rest. While aging is the main risk factor, epidemiological evidence suggests that the exposure to environmental toxicants, mainly pesticides, metals and solvents could increase the risk of developing neurodegenerative conditions.Oxidative stress in neurodegenerative diseases: Mitochondria function impacts cell respiratory processes, metabolism, energy production, intracellular signaling, free radical production, and apoptosis. In neurodegenerative diseases, mitochondrial dysfunction is associated with a compromised energy production, impaired calcium buffering, activation of proteases and phospholipases, and increased oxidative stress. Oxidative stress induced microglial cells activation, protein aggregation, neuroinflammation and mitochondrial dysfunction lead to neuronal deaths in these disorders.Role of nutrition: Neurodegenerative disease is not curable, but treatment is available to manage the symptoms and slow down the disease progression. The drugs for treating these diseases only reduce the cognitive impairment and behavioral problems, but do not stop the progression of neurodegeneration. Healthy diet, lifestyle improvement and nutraceuticals targeting of oxidative stress, inflammation, abnormal mitochondrial dynamics and the mitochondrial interaction with abnormal disease-related proteins and assessment of impact of environmental contaminants including occupational exposures to pesticides, can be a promising approach in the treatment of neurodegenerative diseases.Conclusion: These innovations can be benchmarked on firm understanding of nutrigenomics and the personalized management of individuals at risk.
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Doença de Alzheimer/terapia , Exposição Ambiental/efeitos adversos , Nutrigenômica/métodos , Terapia Nutricional/métodos , Doença de Parkinson Secundária/terapia , Doença de Alzheimer/induzido quimicamente , Dieta Saudável/métodos , Humanos , Metais/toxicidade , Mitocôndrias/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson Secundária/induzido quimicamente , Praguicidas/toxicidade , Medicina de Precisão/métodos , Solventes/toxicidadeRESUMO
AIM: This study examined the use and adverse reactions of second-generation antipsychotics (SGAs), alone or combined with other psychotropic medication, to identify areas for standardising prescribing and monitoring practices. METHODS: We conducted a retrospective study at Tampere University Hospital, Finland, involving 128 patients (81% boys) who were under 13 years old at SGA initiation and had SGA treatment between October 2013 and October 2014. RESULTS: The median age at baseline was 9.4 years. Weight gain was reported as an adverse reaction in 33%, but an increase in standardised body mass index, adjusted for age and sex (BMI z-score), was detected in 75% of patients with sufficient data. The statistically significant median changes during the study were an increase of 0.46 in BMI z-score, a reduction of 0.25 mmol/L in fasting plasma high-density lipoprotein and an increase of 0.28 mmol/L in triglyceride values. The weight gain was most apparent in patients treated with just an SGA or SGA plus melatonin. Patients treated with an SGA plus medication for attention deficit hyperactivity disorder were less likely to gain weight. CONCLUSION: SGA-induced metabolic disturbances remained partly unrecognised in children under 13 years of age and more systematic monitoring is needed.
Assuntos
Antipsicóticos , Adolescente , Antipsicóticos/efeitos adversos , Criança , Finlândia/epidemiologia , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Aumento de PesoRESUMO
NEW FINDINGS: What is the central question of this study? Does glucocorticoid excess disrupt brown adipose tissue (BAT) phenotype and function? What is the main finding and its importance? Glucocorticoid excess induced an extensive remodelling of interscapular BAT, resulting in a white-like phenotype in association with metabolic disturbances. Glucocorticoids might be an important modulator of BAT physiology and BAT may have a role in pathophysiology of metabolic disturbances induced by glucocorticoid excess. ABSTRACT: In mammals, brown adipose tissue (BAT) is centrally involved in energy metabolism. To test the hypothesis that glucocorticoid excess disrupts BAT phenotype and function, male Wistar rats were treated with corticosterone in drinking water for 21 days. To confirm induction of glucocorticoid excess and metabolic disturbances, adrenal weight, corticotrophin releasing hormone mRNA levels and corticosterone serum levels were measured and a glucose tolerance test and serum triacylglycerol analyses were performed. Adipose tissue deposits were excised, weighed and evaluated by a set of biochemical, histological and molecular procedures, including thin-layer chromatography, histochemistry, immunohistochemistry, quantitative real-time polymerase chain reaction, high-resolution oxygraphy, ATP synthesis and enzymatic activity measurements. The approach was successful in induction of glucocorticoid excess and metabolic disturbances. Lower body weight and increased adiposity were observed in corticosterone-treated rats. Interscapular brown adipose tissue (iBAT) showed higher sensitivity to glucocorticoids than other fat deposits. The treatment induced lipid accumulation, unilocular rearrangement, increased collagen content and decreased innervation in iBAT. Furthermore, expression of Prdm16 (P < 0.05), Ucp1 (P <0.05) and Slc7a10 (P <0.05) mRNA decreased, while expression of Fasn (P <0.05) and Lep (P <0.05) mRNA increased in brown adipose tissue. Also, the levels of UCP1 diminished (P <0.001, 2.5-fold). Finally, lower oxygen consumption (P <0.05), ATP synthesis (P <0.05) and mitochondrial content (P <0.05) were observed in iBAT of glucocorticoid-treated rats. Glucocorticoid excess induced an extensive remodelling of interscapular brown adipose tissue, resulting in a white-like phenotype in association with metabolic disturbances.
Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Corticosterona/farmacologia , Tecido Adiposo Marrom/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Metabolismo Energético/efeitos dos fármacos , Glucocorticoides/metabolismo , Teste de Tolerância a Glucose/métodos , Masculino , Proteínas de Membrana/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Fatores de Transcrição/metabolismo , Proteína Desacopladora 1/metabolismoRESUMO
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 ~70â»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.
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Glioma/genética , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Epigenômica , Humanos , Isocitrato Desidrogenase/genética , Mutação/genéticaRESUMO
The stages of postoperative metaphylaxis, drugs used for correction of metabolic disturbances are reviewed. In addition, the basic principles of drug metaphylaxis in various types of stone formation are described.
Assuntos
Cálculos Urinários , Humanos , Período Pós-Operatório , Cálculos Urinários/tratamento farmacológicoRESUMO
All theories of stone formation are based on the common condition, which is the supersaturation of stone-forming elements. The microelements involved in the stone formation, the most common metabolic disorders and their role in stone formation are discussed.
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Doenças Metabólicas , Cálculos Urinários , Urolitíase , Oxalato de Cálcio , Humanos , Incidência , Fatores de Risco , Cálculos Urinários/epidemiologia , Urolitíase/epidemiologiaRESUMO
The place and indications for recurrence prevention of urinary stone disease, general principles of recurrence prevention, role of mineral water and changes of dietary habits during recurrence prevention are reviewed in the article.
Assuntos
Águas Minerais/uso terapêutico , Cálculos Urinários/prevenção & controle , Humanos , Recidiva , Fatores de Risco , Prevenção SecundáriaRESUMO
The role of dairy foods and related nutrients in cardiometabolic health aetiology is poorly understood. We investigated longitudinal associations between the metabolic syndrome (MetS) and its components with key dairy product exposures. We used prospective data from a bi-racial cohort of urban adults (30-64 years at baseline (n 1371)), the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS), in Baltimore City, MD (2004-2013). The average of two 24-h dietary recalls measured 4-10 d apart was computed at baseline (V1) and follow-up (V2) waves. Annual rates of change (Δ) in dairy foods and key nutrients were estimated. Incident obesity, central obesity and the MetS were determined. Among key findings, in the overall urban adult population, both cheese and yogurt (V1 and Δ) were associated with an increased risk of central obesity (hazard ratio (HR) 1·13; 95 % CI 1·05, 1·23 per oz equivalent of cheese (V1); HR 1·21; 95 % CI 1·01, 1·44 per fl oz equivalent of yogurt (V1)]. Baseline fluid milk intake (V1 in cup equivalents) was inversely related to the MetS (HR 0·86; 95 % CI 0·78, 0·94), specifically to dyslipidaemia-TAG (HR 0·89; 95 % CI 0·81, 0·99), although it was directly associated with dyslipidaemia-HDL-cholesterol (HR 1·10; 95 % CI 1·01, 1·21). Furthermore, ΔCa and ΔP were inversely related to dyslipidaemia-HDL and MetS incidence, respectively, whereas Δdairy product fat was positively associated with incident TAG-dyslipidaemia and HDL-cholesterol-dyslipidaemia and the MetS. A few of those associations were sex and race specific. In sum, various dairy product exposures had differential associations with metabolic disturbances. Future intervention studies should uncover how changes in dairy product components over time may affect metabolic disorders.
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Laticínios , Dieta , Síndrome Metabólica/epidemiologia , Obesidade/epidemiologia , Adulto , Índice de Massa Corporal , Colesterol/sangue , Feminino , Seguimentos , Humanos , Incidência , Masculino , Rememoração Mental , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , População Urbana , Circunferência da CinturaRESUMO
Urinary stone disease is one of the most actively progressing diseases, which are associated with metabolic disturbances and are influenced by the genetic, environmental factors and lifestyle \. In the article the current views on initiation factors of stone formation and theories of stone formation are reviewed. The factors that play an important role in the activation and inhibition of nucleation and aggregation of stone-forming substances are discussed. All theories of stone formation are based on the common condition, which is the supersaturation of stone-forming elements. The microelements involved in the stone formation, the most common metabolic disorders and their role in stone formation are discussed.
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Doenças Metabólicas , Cálculos Urinários , Humanos , Incidência , Recidiva , Fatores de RiscoRESUMO
In the study, comparative analysis before and after the air cryotherapy for the following parameters: total cholesterol (using a set of reagents CHOL_2, automatic biochemical analyzer ADVIA 2400( Siemens), glucose (using a set of reagents Glucose Hexokinase II, automatic biochemical analyzer ADVIA 2400 (Siemens), cholesterol of low-density lipoproteins (using the set of reagents of L-HDL, automatic biochemical analyzer ADVIA 2400 (Siemens). The number of oxidized lipoproteins (LP) was determined by the method of the Muzya G. I., the amount of LP resistant to oxidation was determined by the Ragino Yu.I. The clinical group consisted of 30 people with a verified diagnosis of metabolic syndrome, the average age of which was 45.3±3.7 years. Patients of the clinical group received a course of cryotherapy by the method, including the presence in the pre -chamber at t0 -600C for 30 seconds, then in the main chamber at t 0-110-1200C for 180 seconds. Procedures were released again with an interval of 20 minutes, daily within 10 days. Statistical processing of the obtained data was carried out according to conventional methods with the determination of the arithmetic mean, the mean error using the program STADIA version 6.0. The significance of differences in the clinical group before and after the correction was judged by the Student's t-test value after checking the distribution for normality. Differences corresponding to the probability error p<0.05 were considered statistically significant. In patients of the clinical group with metabolic syndrome before treatment, elevated levels of total serum cholesterol by 24.3% and glucose by 12.8% relative to normal values were found. After the course of General air cryotherapy, the total number of low-density lipoproteins decreased by 15.47%, total serum cholesterol by 32.30%, while the serum glucose level decreased by 11.8% compared to the indicators registered in the clinical group before cryotherapy.
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Crioterapia , Síndrome Metabólica/terapia , Adulto , Glicemia/análise , Colesterol/sangue , Humanos , Pessoa de Meia-Idade , Triglicerídeos/sangueRESUMO
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.
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Biomarcadores/sangue , Infertilidade Masculina/genética , Síndrome Metabólica/genética , MicroRNAs/sangue , Adulto , Estudos de Casos e Controles , Hormônio Foliculoestimulante/sangue , Humanos , Infertilidade Masculina/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Triglicerídeos/sangue , Triglicerídeos/genéticaRESUMO
The properties of spermatogonial stem cells, endothelial progenitor cells, and the epithelial progenitors of C57Bl/6 mice under conditions of metabolic disorders were studied using the model of busulfan-induced suppression of spermatogenesis and in vitro culture technique. Spermatogonial stem cells CD117-CD90+ and epithelial progenitors CD45-CD31-Sca-1+CD49f+ derived from the testes of mice with metabolic disturbances demonstrated 17- and 28-fold increase in the respective cell mass and generated cell colonies in vitro. In contrast, spermatogonial stem cells with immune phenotype CD51-CD24+CD52+ had reduced selfrenewal capacity. Spermatogonial stem cells CD117-CD90+ and CD117+CD90+ as well as endothelial progenitors CD45-CD31+ derived from the testes of donor mice with metabolic disorders demonstrated high transplantation capacity in C57Bl/6 mouse testes damaged by cytostatic busulfan.
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Células Progenitoras Endoteliais/citologia , Células-Tronco/citologia , Animais , Bussulfano/farmacologia , Antígeno CD24/metabolismo , Antígeno CD52/metabolismo , Células Progenitoras Endoteliais/efeitos dos fármacos , Inflamação/metabolismo , Integrina alfaV/metabolismo , Masculino , Doenças Metabólicas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Proto-Oncogênicas c-kit/metabolismo , Espermatogênese/efeitos dos fármacos , Espermatogônias/citologia , Espermatogônias/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos , Testículo/efeitos dos fármacos , Testículo/metabolismo , Antígenos Thy-1/metabolismoRESUMO
OBJECTIVE: The purpose of this review is to provide an overview of possible medical complications of binge-eating disorder (BED). METHOD: Literature on BED, both in obese and nonobese patients, was reviewed. RESULTS: A growing literature suggests that BED independently may increase the likelihood of developing components of the metabolic syndrome, and that LOC eating in children may contribute to weight gain and metabolic disturbances. Limited evidence suggests that other organ systems may be affected by BED as well. DISCUSSION: Additional prospective studies are needed. Although the results of the available studies are not definitive and provide somewhat mixed results, there does appear to be a clear suggestion of an increased risk for the development of components of the metabolic syndrome in adults and children.