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Abstract: 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.

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's clinical, endocrinological, and metabolic parameters concerning hyperandrogenism severity., Results: 314 women (mean age 27.3 ± 4.6; mean body mass index (BMI) 25.7 ± 5.6) with PCOS, were divided into terciles according to T concentrations: <0.64 ng/mL (group 1), 0.64 to 0.84 ng/mL (Group 2) and >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 = -0.36; p < 0.0001) and positively with Ferriman-Gallway score (FG) (r = 0.33; p < 0.0001), luteinizing hormone (LH) (r = 0.19; p < 0.0001) and dehydroepiandrosterone sulfate (DHEAS) (r = 0.52; p < 0.0001). Positive correlation between BMI and hirsutism (r = 0.16; p < 0.0001), total cholesterol (TC) (r = 0.18; p < 0.0001), low-density lipoprotein (LDL) (r = 0.29; p < 0.0001), and triglycerides (TG) (r = 0.40; p < 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., Competing Interests: The authors declare no conflict of interest.

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 20-65 years undergoing a health check during 2016-2017, 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 < 0.001), systolic blood pressure (BP) ( p = 0.005), diastolic BP ( p < 0.001), and glycated hemoglobin (HbA1c) ( p < 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 < 0.001), diastolic BP ( p = 0.003), and HbA1c ( p < 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 ≥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.

Objective: Impaired 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 Methods: The 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., Results: Various 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., Conclusions: This 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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. [ABSTRACT FROM AUTHOR]

Fpidemiology studies have confirmed a hypothesis on pre-natal risk determination for metabolic syndrome (MS), arterial hypertension (AH), and coronary heart disease (CHD). Gestational diabetes (GD) and obesity are typical metabolic disturbances in pregnancy. Insulin resistance (IR) development at early gestation stages results in fat tissue proliferation and increased feto-placental nutritious value by late pregnancy stages, when fetus weight increases by 70%. Increased IR in mother provides reproductive benefit in case of under-nutrition and over-working, at the same time being able to result in GD, when combined with calorie-rich diet and sedentary lifestyle. Increased IR and pre-conception obesity increase macrosomia and fetus overweight risk. Overweight children of GD mothers have increased risk of juvenile obesity and type 2 diabetes mellitus (DM-2). Decreased fetal height and body size in pregnancy and early post-natal period could also result in DM and MS later in life. In spite of low cardiovascular morbidity in young women, gestational hyperglycemia combined with pre-pregnancy obesity, as well as gestational hypertensive syndrome, significantly increase cardiovascular risk. Women with pregnancy-diagnosed metabolic disturbances and AH, as well as their children, need to be actively followed-up and treated, if necessary.

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.

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.

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.

Introduction: The prognosis for severe burns has improved significantly over the past 50 years. Meanwhile, burns have become an affliction mainly affecting the less well-developed regions of the world. Early excision and skin grafting has led to major improvements in therapeutic outcomes., Areas Covered: The purpose of this article is to survey the use of pharmacotherapy to treat different pathophysiological complications of burn injury. The author, herein, discusses the use of drug treatments for a number of systemic metabolic disturbances including hyperglycemia, elevated catabolism, and gluconeogenesis., Expert Opinion: Advancements in personalized and molecular medicine will make an impact on burn therapy. Similarities between severe burns and other critically ill patients will lead to cross-fertilization between different medical specialties. Furthermore, advances in stem cells and tissue regeneration will lead to improved healing and less lifelong disability. Indeed, research in new drug therapy for burns is actively progressing for many different complications.

Background: Schizophrenia is a complex medical entity with a reduced life expectancy, mostly due to an increased prevalence of cardiovascular diseases compared to the general population. An unbalanced immune response and a pro-inflammatory state might underlie this process. In treated patients, abnormal white blood cell (WBC), lymphocyte and neutrophil count suggests atypical immune response related to clinical variables. We aimed to test the hypothesis that newly diagnosed naïve patients with non-affective psychosis would show abnormal blood cell count values after controlling for potential confounding factors compared to matched controls., Methods: Seventy-five patients were compared with 80 controls matched for age, gender, body mass index and smoking. Analyses were conducted before and after controlling for smoking., Results: Patients and controls displayed similar mean values (×10 3 /μL [SD]) for WBC count 7.02 [2.2] vs 6.50 [1.7] (P = .159), neutrophil count 4.25 [1.8] vs 3.84 [1.3] (P = .110) and monocyte count 0.43 [0.2] vs 0.40 [0.1] (P = .326). After controlling for smoking, 38 non-smoking patients showed a higher WBC and neutrophil count compared with 49 matched controls. Respective means of 7.01 [2.2] vs 5.97 [1.4] (P = .011) for WBC and 4.24 [1.9] vs 3.51 [1.2] (P = .028) for neutrophil count. Monocyte count showed an increased mean value 0.43 [0.2] vs 0.36 [0.1] with a trend towards signification (P = .063)., Conclusions: These results suggest that abnormal immune response is present before the effects of medication and other confounders had taken place. Increased immune parameters might underlie the high ratio of medical co-morbidities described in schizophrenia., (© 2017 John Wiley & Sons Australia, Ltd.)

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.

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)., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background and Aim: The aim of this study was to examine the relationship between new obesity-related indexes, anthropometric and biochemical parameters, and body composition in individuals with obesity., Methods: The study group consisted of 72 women and 34 men, aged 39.0 ± 5.9 years, with a mean body mass index (BMI) of 32.6 ± 2.4 kg/m², admitted for body weight reduction. In all participants body weight (BW), height, waist circumference (WC), hip circumference (HC), BMI, waist-to-hip-ratio (WHR), visceral adiposity index (VAI), body adiposity index (BAI), and waist-to-height ratio (WHtR) were assessed. Using bioelectrical impedance (BIA, TANITA MC 180M) the following parameters were obtained: the level of visceral adipose tissue (VAT) and body fat percentage (FM%). Serum concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides (TG), glucose, insulin, and insulin resistance (HOMA-IR) were determined., Results: It was observed that almost all the studied indicators: WC, WHtR, BAI, VAI, and BMI, positively correlated with VAT estimated by bioimpedance, but only VAI, WC, and WHtR were strongly associated with glucose and lipid disturbances in the obese. BAI and BMI correlated with total FM%, while WC, WHtR, and VAI correlated with total body weight., Conclusions: The results indicate that VAI, WC, and WHtR can be useful in the assessment of increased VAT accumulation associated with disturbances in glucose and lipid metabolism. BAI should be calculated separately for each sex, then it could be also useful for the prediction of disturbances in glucose metabolism. However, further studies are needed to recognise cut-off values for BAI, as a marker of body fatness, associated with adverse health effects.

Curcumae Radix (CR) and Glycyrrhizae Radix et Rhizoma (GR) extracts have been used as health supplements in traditional medicine. This study was performed to evaluate the effects of combined CR and GR extracts (CR+GR) on metabolic complications related menopausal symptoms. We found a significant results that CR+GR extracted using ethanol stimulated the growth of MCF-7 cells in estrogen activity and was attenuated in lipid deposition of HepG2 cells treated with MβCD compared to CR and GR treatments each. To investigate the situation, an experimental menopause rat model with dyslipidemia was induced by surgical bilateral ovariectomy (OVX) and high fat high cholesterol (HFHC) diet in female rats. OVX rats fed HFHC (OVX-HFHC) showed a shift in weight gain, elevated serum cholesterol, altered liver enzymatic parameters and enhanced liver injury compared to the NC and HFHC groups. However, administration of CR+GR, in particular 200 or 450 mg/kg/day, inhibited the increase in body weight gain and lipid metabolic disturbances, lowering total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) compared to the OVX-HFHC group. Furthermore, CR+GR (200 or 450 mg/kg/day) ameliorated the serum levels of the liver enzymes aspartate aminotransferase (AST) and alanine transaminase (ALT) compared to the OVX-HFHC group. Moreover, CR+GR (200 or 450 mg/kg/day) attenuated not only hepatic steatosis but also larger adipocytes. Our study demonstrated that combined treatment with CR and GR attenuated metabolic complications induced by OVX and HFHC diet, suggesting that this effect may regulate and prevent the acceleration of cardiovascular disease (CVD) after menopause.

Objective: To study the association of adrenal and ovarian androgen levels with metabolic parameters in a large cohort of women with polycystic ovary syndrome (PCOS). Design: Cross-sectional study. Setting: Outpatient clinic of an academic hospital. Patient(s): Six hundred twenty-two women with PCOS. Intervention(s): None. Main Outcome Measure(s): Analysis of the association of endocrine dehydroepiandrosterone sulfate (DHEAS) and free testosterone (FT) parameters with metabolic measurements. Result(s): In multivariate adjusted logistic regression analyses, the odds ratio (OR) for insulin resistance was statistically significantly higher (4.42, range: 2.26–8.67) for women with PCOS who had elevated FT levels compared with the women with normal DHEAS and FT levels (reference group). We found no statistically significant differences when women with PCOS with elevated DHEAS or a combined elevation of DHEAS and FT levels were compared with the reference group. Women with PCOS and a high DHEAS/FT ratio had a more beneficial metabolic profile compared with the women with a low DHEAS/FT ratio. In multivariate adjusted binary logistic regression analyses, we found a statistically significantly lower risk for insulin resistance in the women with PCOS in the highest DHEAS/FT-ratio quartile compared with women with PCOS in the lowest quartile (OR 0.35, range: 0.14–0.89). Conclusion(s): Our results suggest that the distinction between adrenal and ovarian hyperandrogenism is important when evaluating metabolic risk in PCOS. [ABSTRACT FROM AUTHOR]

Erythrocyte transketolase activity and guanidino compounds in hemodialysis patients Background The toxic effects of guanidino compounds on enzymatic activity in uremic patients are known. Thus, we determined the hemodialysis (HD) impact on this toxicity. Methods The 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. Results At 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. Conclusion There 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. [ABSTRACT FROM AUTHOR]