The independent association between parathyroid hormone levels and hyperuricemia: a national population study

Introduction

Increased frequencies of hyperuricemia and gout have been associated with primary hyperparathyroidism, and recent clinical trials of parathyroid hormone (PTH) have reported hyperuricemic adverse events. We evaluated the potential population impact of PTH on serum uric acid (SUA) levels by using a nationally representative sample of United States adults.

Methods

By using data from 8,316 participants aged 18 years and older in the National Health and Nutrition Examination Survey 2003 to 2006, we examined the relation between serum PTH and SUA levels with weighted linear regression. Additionally, we examined the relation with hyperuricemia by using weighted logistic regression.

Results

SUA levels increased with increasing serum PTH concentration. After adjusting for age, sex, dietary factors, glomerular filtration rate (GFR), and other potentially related biomarkers (calcium, phosphorus, alkaline-phosphatase, 25-hydroxyvitamin D), the SUA level differences from the bottom (referent) to top quintiles of serum PTH levels were 0, 8, 13, 14, and 19 μM (95% CI, 12 to 26; P for trend, < 0.001). These estimates were larger among renally impaired individuals (multivariate SUA difference between the extreme quintiles of PTH, 26 versus 15 μM among those with GFR ≥ 60 versus < 60 ml/min per 1.73 m², respectively) (P for interaction = 0.004). The odds of hyperuricemia by various definitions increased with increasing PTH levels as well (multivariate P values for trend, < 0.05).

Conclusions

These nationally representative data indicate that serum PTH levels are independently associated with serum uric acid levels and the frequency of hyperuricemia at the population level.     

Association between the prevalence of hyperuricemia and reproductive hormones in polycystic ovary syndrome

Background

The prevalecne of hyperuricemia in polycystic ovary syndrome (PCOS) is still uncertain. We aimed to investigate the prevalence of hyperuricemia in PCOS and to determine the influence of reproductive hormones on uric acid concentration.

Methods

This retrospective cross-sectional study was performed at a large reproductive medicine center. Between March 2007 and October 2016, a total of 1,183 women with PCOS and 10,772 women without PCOS were included. PCOS was diagnosed according to the Rotterdam criteria. Anthropometric parameters, blood pressure, uric acid, reproductive hormones, glucose and lipids were measured in all subjects.

Results

The serum uric acid (SUA) level was higher in women with PCOS than in women without PCOS. The prevalence of hyperuricemia in women with PCOS (25.48%) was significantly higher than that in women without PCOS (8.74%). Analysis stratified for age and body mass index (BMI) showed that both the SUA level and the prevalence of hyperuricemia were higher in women with PCOS of different age and BMI groups than in women without PCOS. After adjusting for age, BMI and estimated glomerular filtration rate (eGFR), logistic regression analysis revealed that the luteinizing/follicle-stimulating hormone (LH/FSH) ratio (odds ratio (OR)?=?1.20, 95% CI?=?1.01–1.43) and testosterone level (OR?=?1.56, 95% CI?=?1.27–1.90) were positively associated with the prevalence of hyperuricemia in females with PCOS.

Conclusions

The serum uric acid (SUA) level and the prevalence of hyperuricemia markedly increased in women with PCOS. The testosterone level was positively associated with the SUA level and the prevalence of hyperuricemia in females with PCOS.

     

The baseline levels and risk factors for high-sensitive C-reactive protein in Chinese healthy population

Background

Recent studies show that C-reactive protein (CRP) is not only a biomarker but also a pathogenic mediator contributing to the development of inflammation and ageing-related diseases. However, serum levels of CRP in the healthy ageing population remained unclear, which was investigated in the present study.

Methods

Serum levels of high sensitive C-reactive protein (hs-CRP), glucose (Glu), triglyceride (TG), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), superoxide dismutase (SOD), serum creatinine (SCr), serum uric acid (SUA) were measured in 6060healthy subjects (3672 male and 2388 female, mean age:45.9 years) who received routine physical examination at Sun Yat-sen Memorial Hospital, Guangzhou, China.

Results

In total of 6060 healthy people, serum levels of hs-CRP were significantly increased with ageing (P?<?0.05), particularly in those with age over 45-year-old (1.31[0.69–2.75] vs 1.05[0.53–2.16]mg/L, P?<?0.001). Interestingly, levels of serum hs-CRP were significantly higher in male than female population (1.24[0.65–2.57] vs 1.07[0.53–2.29]mg/L, P?<?0.001). Correlation analysis also revealed that serum levels of hs-CRP positively correlated with age and SUA, but inversely correlated with serum levels of HDL-c and SOD (all P?<?0.05).

Conclusions

Baseline levels of serum hs-CRP are increased with ageing and are significantly higher in male than female healthy population. In addition, elevated serum levels of hs-CRP are also associated with increased SUA but decreased HDL-c and SOD. Thus, serum levels of hs-CRP may be an indicator associated with ageing in healthy Chinese population.

     

Association of Serum Uric Acid and Coronary Artery Disease in Premenopausal Women

Objective

To date, no study in the published literature has investigated the role of various serum uric acid (SUA) concentrations in the development of angiographically-proven coronary artery disease (CAD) in premenopausal women. Therefore, the aim of this study was to investigate the role SUA levels may play in the prevalence, severity, and prognosis of CAD in premenopausal women.

Methods

This cross-sectional retrospective study included 607 premenopausal women who had undergone coronary angiography. The CAD diagnosis was based upon stenosis affecting ≥50% of the luminal diameter. Association of the SUA levels with CAD prevalence, severity, and clinical outcomes were assessed by statistical analysis.

Results

In total, 369 (60.8%) of the patients were diagnosed with CAD. The CAD patients had significantly higher SUA levels than those without CAD (5.3±1.9 vs. 4.8±1.7 mg/dL, P = 0.001). The SUA levels were found to be significantly associated with CAD prevalence (P = 0.013). Patients with higher levels of SUA also showed increased rates of multivessel disease and composite end-points, such as major adverse cardiac events. Furthermore, multivariate analysis identified abnormally high levels of uric acid (hyperuricemia) as an independent risk factor for CAD (OR 1.51 (1.11–2.53), P<0.05).

Conclusions

The SUA levels are significantly associated with the prevalence of CAD. The SUA levels may be a predictor for incidence of major cardiovascular events in premenopausal women.     

Association of Maximum Weight with Hyperuricemia Risk: A Retrospective Study of 21,414 Chinese People

Background

Obesity has been demonstrated to be associated with increased serum uric acid (SUA); however, little is known regarding the relationship between maximum weight, or maximum weight fluctuation, and uric acid concentration. Through retrospective means, we determined the association of maximum weight with SUA risk.

Methods

Data of 21,414 participants (8,630 males and 12,784 females) from the 2007-8 China National Diabetes and Metabolic Disorders Study were analyzed for parameters including lifestyle habits, biochemical blood analysis and self-reported maximum weight.

Results

Elevated SUA subjects shared a cluster of demographic features. After adjustment for age, gender, education, smoking, drinking, physical activity, WHR, height, eGFR(evaluate glomerular filtration rate), and diuretic usage, multivariate logistic regression models demonstrated maximum weight was associated with increased risk of elevated SUA level (P<0.001). Duration of maximum weight was related with decreased risk of elevated SUA level (P<0.001). There was a significant correlation between time of weight loss and risk of increased SUA level reduction (P<0.001). Furthermore, our data indicated that the degree of weight loss from maximum weight was another important factor for the risk of increased SUA level reduction (P<0.001). Finally, ROC curve analysis revealed area under the curve was 0.661 (95% CI, 0.647-0.674), statistically significant for maximum weight association with hyperuricemia (P<0.001).

Conclusions

Maximum weight is a strong risk factor for increased uric acid level in the Chinese population, which might serve as a novel clinical indicator suggesting hyperuricemia. Controlling maximum weight, keeping weight to the appropriate range, and maintaining the stable weight may be conducive for decreasing risk of hyperuricemia.     

Liver Fat Content Is Associated with Elevated Serum Uric Acid in the Chinese Middle-Aged and Elderly Populations: Shanghai Changfeng Study

Background and Aims

Although many studies have indicated a relationship between nonalcoholic fatty liver disease (NAFLD) and hyperuricemia, a few studies specifically examining the effects of the severity of liver fat content (LFC) on serum uric acid (SUA) and the presence of hyperuricemia because of the limitation of the examination methods for NAFLD. In this study, we investigate the relationship between the NAFLD and SUA levels in the Chinese population using standardized quantitative ultrasound.

Methods

A community-based study was conducted from May 2010 to December 2012. A total of 4,305 people aged 45 years and above without excessive drinking were enrolled. A standard interview and anthropometric and laboratory blood parameters were collected for each person. The standardized ultrasound hepatic/renal ratio and hepatic attenuation rate was used to quantify LFC.

Results

The prevalence of NAFLD and hyperuricemia was 33.1% and 17.1%, respectively. A total of 23.5% of the NAFLD subjects had hyperuricemia, and their SUA was higher than that of non-NAFLD subjects (327.2±76.8 vs 301.9±77.4 μmol/L, P<0.001). The LFC was positively correlated with SUA (r = 0.130, P<0.001) and an independent factor for SUA (standardized β = 0.054, P<0.001). The OR for the presence of hypreuricemia was 1.175 (95% CI 1.048–1.318; P<0.001) with a 1 SD increase in the log LFC. LFC greater than 10% was related to elevated SUA and an increased presence of hyperuricemia.

Conclusions

LFC accumulation was associated with an increase in the prevalence of hyperuricemia and elevated SUA in our community-based population. LFC greater than 10% is related to the risk for hyperuricemia.     

A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome

Background

Several studies suggest an increase of oxidative stress and a reduction of endothelial function in obstructive sleep apnoea syndrome (OSAS). We assessed the association between OSAS, endothelial dysfunction and oxidative stress. Further aim was to evaluate the effect of nasal continuous positive airway pressure (nCPAP) on oxidative stress and arterial dysfunction.

Methods

We studied 138 consecutive patients with heavy snoring and possible OSAS. Patients underwent unattended overnight home polysomnography. Ten patients with severe OSAS were revaluated after 6?months of nCPAP therapy. To assess oxidative stress in vivo, we measured urinary 8-iso-PGF2?? and serum levels of soluble NOX2-derived peptide (sNOX2-dp). Serum levels of nitrite/nitrate (NOx) were also determined. Flow-mediated brachial artery dilation (FMD) was measured to asses endothelial function.

Results

Patients with severe OSAS had higher urinary 8-iso-PGF2?? (p<0.001) and serum NOX2 and lower NOx. A negative association was observed between FMD and OSA severity. Apnea/hypopnea index was significantly correlated with the indices of central obesity and with urinary 8-isoprostanes (r=0.298, p<0.001). The metabolic syndrome (t=-4.63, p<0.001) and urinary 8-isoprostanes (t=-2.02, p<0.05) were the only independent predictors of FMD. After 6-months nCPAP treatment, a significant decrease of serum NOX2, (p<0.005) and urinary 8-iso-PGF2?? (p<0.01) was observed, while serum NOx showed only a minor increase. A statistically significant increase of FMD was observed (from 3.6% to 7.0%).

Conclusions

The results of our study indicate that patients with OSAS and cardiometabolic comorbidities have increased oxidative stress and arterial dysfunction that are partially reversed by nCPAP treatment.     

Uric acid levels are associated with endothelial dysfunction and severity of coronary atherosclerosis during a first episode of acute coronary syndrome

The role of serum uric acid in coronary artery disease has been extensively investigated. It was suggested that serum uric acid level (SUA) is an independent predictor of endothelial dysfunction and related to coronary artery lesions. However, the relationship between SUA and severity of coronary atherosclerosis evaluated via endothelial dysfunction using peripheral arterial tone (PAT) and the reactive hyperhemia index (RHI) has not been investigated during a first episode of acute coronary syndrome (ACS). The aim of our study was to address this point. We prospectively enrolled 80 patients with a first episode of ACS in a single-center observational study. All patients underwent coronary angiography, evaluation of endothelial function via the RHI, and SUA measurement. The severity of the coronary artery lesion was assessed angiographically, and patients were classified in three groups based on the extent of disease and Gensini and SYNTAX scores. Endothelial function was considered abnormal if RHI?<?1.67. We identified a linear correlation between SUA and RHI (R² =?0.66 P <?0.001). In multivariable analyses, SUA remained associated with RHI, even after adjustment for traditional cardiovascular risk factors and renal function. SUA was associated with severity of coronary artery disease. SUA is associated with severity of coronary atherosclerosis in patients with asymptomatic hyperuricemia. This inexpensive, readily measured biological parameter may be useful to monitor ACS patients.     

Early myocardial dysfunction in streptozotocin-induced diabetic mice: a study using in vivo magnetic resonance imaging (MRI)

Background

Low income individuals with diabetes are at particularly high risk for poor health outcomes. While specialized diabetes care may help reduce this risk, it is not currently known whether there are significant clinical differences across income groups at the time of referral. The objective of this study is to determine if the clinical profiles and medication use of patients referred for diabetes care differ across income quintiles.

Methods

This cross-sectional study was conducted using a Canadian, urban, Diabetes Education Centre (DEC) database. Clinical information on the 4687 patients referred to the DEC from May 2000 – January 2002 was examined. These data were merged with 2001 Canadian census data on income. Potential differences in continuous clinical parameters across income quintiles were examined using regression models. Differences in medication use were examined using Chi square analyses.

Results

Multivariate regression analysis indicated that income was negatively associated with BMI (p < 0.0005) and age (p = 0.023) at time of referral. The highest income quintiles were found to have lower serum triglycerides (p = 0.011) and higher HDL-c (p = 0.008) at time of referral. No significant differences were found in HBA1C, LDL-c or duration of diabetes. The Chi square analysis of medication use revealed that despite no significant differences in HBA1C, the lowest income quintiles used more metformin (p = 0.001) and sulfonylureas (p < 0.0005) than the wealthy. Use of other therapies were similar across income groups, including lipid lowering medications. High income patients were more likely to be treated with diet alone (p < 0.0005).

Conclusion

Our findings demonstrate that low income patients present to diabetes clinic older, heavier and with a more atherogenic lipid profile than do high income patients. Overall medication use was higher among the lower income group suggesting that differences in clinical profiles are not the result of under-treatment, thus invoking lifestyle factors as potential contributors to these findings.     

Neuropeptide-inducible upregulation of proteasome activity precedes nuclear factor kappa B activation in androgen-independent prostate cancer cells

Background

Upregulation of nuclear factor kappa B (NF??B) activity and neuroendocrine differentiation are two mechanisms known to be involved in prostate cancer (PC) progression to castration resistance. We have observed that major components of these pathways, including NF??B, proteasome, neutral endopeptidase (NEP) and endothelin 1 (ET-1), exhibit an inverse and mirror image pattern in androgen-dependent (AD) and -independent (AI) states in vitro.

Methods

We have now investigated for evidence of a direct mechanistic connection between these pathways with the use of immunocytochemistry (ICC), western blot analysis, electrophoretic mobility shift assay (EMSA) and proteasome activity assessment.

Results

Neuropeptide (NP) stimulation induced nuclear translocation of NF??B in a dose-dependent manner in AI cells, also evident as reduced total inhibitor ??B (I??B) levels and increased DNA binding in EMSA. These effects were preceded by increased 20?S proteasome activity at lower doses and at earlier times and were at least partially reversed under conditions of NP deprivation induced by specific NP receptor inhibitors, as well as NF??B, I??B kinase (IKK) and proteasome inhibitors. AD cells showed no appreciable nuclear translocation upon NP stimulation, with less intense DNA binding signal on EMSA.

Conclusions

Our results support evidence for a direct mechanistic connection between the NPs and NF??B/proteasome signaling pathways, with a distinct NP-induced profile in the more aggressive AI cancer state.     

Associations of Serum Uric Acid and SLC2A9 Variant with Depressive and Anxiety Disorders: A Population-Based Study

Background

Limited information exists regarding the association between serum uric acid (SUA) and psychiatric disorders. We explored the relationship between SUA and subtypes of major depressive disorder (MDD) and specific anxiety disorders. Additionally, we examined the association of SLC2A9 rs6855911 variant with anxiety disorders.

Methods

We conducted a cross-sectional analysis on 3,716 individuals aged 35–66 years previously selected for the population-based CoLaus survey and who agreed to undergo further psychiatric evaluation. SUA was measured using uricase-PAP method. The French translation of the semi-structured Diagnostic Interview for Genetic Studies was used to establish lifetime and current diagnoses of depression and anxiety disorders according to the DSM-IV criteria.

Results

Men reported significantly higher levels of SUA compared to women (357±74 µmol/L vs. 263±64 µmol/L). The prevalence of lifetime and current MDD was 44% and 18% respectively while the corresponding estimates for any anxiety disorders were 18% and 10% respectively. A quadratic hockey-stick shaped curve explained the relationship between SUA and social phobia better than a linear trend. However, with regards to the other specific anxiety disorders and other subtypes of MDD, there was no consistent pattern of association. Further analyses using SLC2A9 rs6855911 variant, known to be strongly associated with SUA, supported the quadratic relationship observed between SUA phenotype and social phobia.

Conclusions

A quadratic relationship between SUA and social phobia was observed consistent with a protective effect of moderately elevated SUA on social phobia, which disappears at higher concentrations. Further studies are needed to confirm our observations.     

Hyperuricemia and metabolic syndrome in type 2 diabetes mellitus patients at Hawassa university comprehensive specialized hospital,South West Ethiopia

Background

Metabolic syndrome is a cluster of the most dangerous heart attack risk factors such as diabetes and prediabetes, abdominal obesity, high cholesterol and high blood pressure. Hyperuricemia is a condition in which the serum uric acid concentration is greater than 5.5 mg per deciliter for child and greater than 7.2 and 6.0 mg per deciliters for male and female adults respectively.

Methods

A cross-sectional study was conducted to determine the magnitude of hyperuricemia and associated factors among type 2 diabetes mellitus patients at Hawassa Comprehensive Specialized Hospital (HCSH) from February 28 to May 30 /2017. A random sampling technique was used to include 319 study subjects and a signed consent had been provided by each study subject before running any data collection. An interviewer administered structured questionnaire was used to collect socio-demographic and some clinically useful data. In addition to this, we reviewed the records of the study subjects to obtain other useful clinical data. Five milliliter blood specimen was collected from each study subjects after overnight fasting. A25TM Bio-System Random Access chemistry analyzer was used for blood sample analysis. All data were checked visually, coded and entered into epi-data version 3.4 and statistical analysis was performed using SPSS version 20.0 software. Bi-variate and multivariate logistic regressions were used to determine the association between explanatory and the outcome variables.

Results

The prevalence of hyperuricemia and metabolic syndrome among type 2 diabetic patients in the study area were 33.8%(n?=?106) and 70.1% (n?=?220) respectively. Having age greater or equal to 45 years (AOR: 1.9, CI: 1.-3.2, P value =0.015) and having metabolic syndrome (AOR: 2.6, CI: 1.5–4.7, P value?=?0.001) were the determinant variables for hyperuricemia among type 2 diabetic patients.

Conclusion

There was high prevalence of hyperuricemia among type 2 diabetic patients with high prevalence of metabolic syndrome. Therefore, regular health information about life style modification, early diagnosis and treatment for hyperuricemia and metabolic syndrome are essential to reduce hyperuricemia and metabolic syndrome in type 2 diabetic patients.

     

Sendai virus-based liposomes enable targeted cytosolic delivery of nanoparticles in brain tumor-derived cells

Background

Nanogold has been investigated in a wide variety of biomedical applications because of the anti-inflammatory properties. The purpose of this study was to evaluate the effects of TPU (Therapeutic Pulsed Ultrasound) with gold nanoparticles (GNP) on oxidative stress parameters and the expression of pro-inflammatory molecules after traumatic muscle injury.

Materials and methods

Animals were divided in nine groups: sham (uninjured muscle); muscle injury without treatment; muscle injury + DMSO; muscle injury + GNP; muscle injury + DMSO + GNP; muscle injury + TPU; muscle injury + TPU + DMSO; muscle injury + TPU + GNP; muscle injury + TPU + DMSO + GNP. The ROS production was determined by concentration of superoxide anion, modulation of antioxidant defenses was determined by the activity of superoxide dismutase, catalase and glutathione peroxidase enzymes, oxidative damage determined by formation of thiobarbituric acid-reactive substance and protein carbonyls. The levels of interleukin-1?? (IL-1??) and tumor necrosis factor-?? (TNF-??) were measured as inflammatory parameters.

Results

Compared to muscle injury without treatment group, the muscle injury + TPU + DMSO + GNP gel group promoted a significant decrease in superoxide anion production and lipid peroxidation levels (p < 0.050). It also showed a significant decrease in TNF-?? and IL-1?? levels (p < 0.050) when compared to muscle injury without treatment group.

Conclusions

Our results suggest that TPU + DMSO + GNP gel presents beneficial effects on the muscular healing process, inducing a reduction in the production of ROS and also the expression of pro-inflammatory molecules.     

BMPR2 expression is suppressed by signaling through the estrogen receptor

Background

Low endogenous testosterone levels have been shown to be a risk factor for the development of cardiovascular disease and cardiovascular benefits associated with testosterone replacement therapy are being advocated; however, the effects of endogenous testosterone levels on acute coronary vasomotor responses to androgen administration are not clear. The objective of this study was to compare the effects of acute androgen administration on in vivo coronary conductance and in vitro coronary microvascular diameter in intact and castrated male swine.

Methods

Pigs received intracoronary infusions of physiologic levels (1?C100 nM) of testosterone, the metabolite 5??-dihydrotestosterone, and the epimer epitestosterone while left anterior descending coronary blood flow and mean arterial pressure were continuously monitored. Following sacrifice, coronary arterioles were isolated, cannulated, and exposed to physiologic concentrations (1?C100 nM) of testosterone, 5??-dihydrotestosterone, and epitestosterone. To evaluate effects of the androgen receptor on acute androgen dilation responses, real-time PCR and immunohistochemistry for androgen receptor were performed on conduit and resistance coronary vessels.

Results

In vivo, testosterone and 5??-dihydrotestosterone produced greater increases in coronary conductance in the intact compared to the castrated males. In vitro, percent maximal dilation of microvessels was similar between intact and castrated males for testosterone and 5??-dihydrotestosterone. In both studies epitestosterone produced significant increases in conductance and microvessel diameter from baseline in the intact males. Androgen receptor mRNA expression and immunohistochemical staining were similar in intact and castrated males.

Conclusions

Acute coronary vascular responses to exogenous androgen administration are increased by endogenous testosterone, an effect unrelated to changes in androgen receptor expression.     

MicroRNA-34a modulates genes involved in cellular motility and oxidative phosphorylation in neural precursors derived from human umbilical cord mesenchymal stem cells

Background

Uric acid is the primary byproduct of purine metabolism. Hyperuricemia is associated with body mass index (BMI), sex, and multiple complex diseases including gout, hypertension (HTN), renal disease, and type 2 diabetes (T2D). Multiple genome-wide association studies (GWAS) in individuals of European ancestry (EA) have reported associations between serum uric acid levels (SUAL) and specific genomic loci. The purposes of this study were: 1) to replicate major signals reported in EA populations; and 2) to use the weak LD pattern in African ancestry population to better localize (fine-map) reported loci and 3) to explore the identification of novel findings cognizant of the moderate sample size.

Methods

African American (AA) participants (n = 1,017) from the Howard University Family Study were included in this study. Genotyping was performed using the Affymetrix^® Genome-wide Human SNP Array 6.0. Imputation was performed using MACH and the HapMap reference panels for CEU and YRI. A total of 2,400,542 single nucleotide polymorphisms (SNPs) were assessed for association with serum uric acid under the additive genetic model with adjustment for age, sex, BMI, glomerular filtration rate, HTN, T2D, and the top two principal components identified in the assessment of admixture and population stratification.

Results

Four variants in the gene SLC2A9 achieved genome-wide significance for association with SUAL (p-values ranging from 8.88 × 10^-9 to 1.38 × 10^-9). Fine-mapping of the SLC2A9 signals identified a 263 kb interval of linkage disequilibrium in the HapMap CEU sample. This interval was reduced to 37 kb in our AA and the HapMap YRI samples.

Conclusions

The most strongly associated locus for SUAL in EA populations was also the most strongly associated locus in this AA sample. This finding provides evidence for the role of SLC2A9 in uric acid metabolism across human populations. Additionally, our findings demonstrate the utility of following-up EA populations GWAS signals in African-ancestry populations with weaker linkage disequilibrium.     

Can the positive aromatic ring be as ��-electron donor in ��-halogen bond? A MP2 theoretical investigation on the unusual ��-halogen bond interaction between three-membered ring \left( {\hbox{BNN}} \right)_3^{+} and X1X2 (X1, X2?=?F, Cl, Br)

The unusual ??-halogen bond interactions are investigated between $ \left( {\hbox{BNN}} \right)_3^{+} $ and X1X2 (X1, X2?=?F, Cl, Br) employing MP2 at 6-311?+?G(2d) and aug-cc-pVDZ levels according to the ??CP (counterpoise) corrected potential energy surface (PES)?? method. The order of the ??-halogen bond interactions and stabilities of the complexes are obtained to be $ \left( {\hbox{BNN}} \right)_3^{+} \ldots {{\hbox{F}}_2} < \left( {\hbox{BNN}} \right)_3^{+} \ldots {\hbox{ClF < }}\left( {\hbox{BNN}} \right)_3^{+} \ldots {\hbox{C}}{{\hbox{l}}_2} < \left( {\hbox{BNN}} \right)_3^{+} \ldots {\hbox{BrCl}}\quad { < }\quad \left( {\hbox{BNN}} \right)_3^{+} \ldots {\hbox{B}}{{\hbox{r}}_2}\quad { < }\quad \left( {\hbox{BNN}} \right)_3^{+} \ldots {\hbox{BrF}}{.} $ at MP2/aug-cc-pVDZ level. The analyses of the Mulliken charge transfer, natural bond orbital (NBO), atoms in molecules (AIM) theory and electron density shifts reveal that the nature of the ??-halogen bond interaction in the complexes of ClF, BrF and BrCl might partly be charge transfer from the delocalized ??-HOMO orbital of $ \left( {\hbox{BNN}} \right)_3^{+} $ to X1X2. This result suggests that the positive aromatic ring $ \left( {\hbox{BNN}} \right)_3^{+} $ might act as a ??-electron donor to form the ??-halogen bond.

Undifferentiated embryonal sarcoma of the liver mimicking acute appendicitis. Case report and review of the literature

Background

Parathyroid carcinoma is a rare cause of primary hyperparathyroidism and may be associated with significant disease related morbidity and mortality. Preoperative diagnosis remains a challenge, which may jeopardize appropriate and successful patient treatment.

Case presentation

We report a case of parathyroid carcinoma diagnosed in a 60-year-old woman that presented with a tender nodule located at the left lower thyroid pole and had been present for several years. Ultrasound examination revealed a 2.7 × 1.6 × 2.7 cm mass within the lower left lobe of the thyroid with cystic and solid areas. Lab measurement of the intact PTH level revealed it to be three times the upper limit of normal and the serum calcium level was within normal limits. A left thyroid lobectomy and isthmusectomy was carried out. Histopathological evaluation was diagnostic for a parathyroid carcinoma. At greater than two years of follow-up, the patient has had no evidence of disease recurrence and her serum PTH and calcium levels have remained within normal.

Conclusion

Parathyroid carcinoma is a rare endocrine tumor which must be considered in the differential diagnosis of a nodular thyroid mass. En bloc resection remains the treatment of choice for this malignancy. Disease prognosis is influenced by the extent of the initial resection, the presence of metastases, and adequate long-term follow-up.     

Genetic testing in diffuse parenchymal lung disease

Background

Mutations in SCO2 cause cytochrome c oxidase deficiency (COX) and a fatal infantile cardioencephalomyopathy. SCO2 encodes a protein involved in COX copper metabolism; supplementation with copper salts rescues the defect in patients?? cells. Bezafibrate (BZF), an approved hypolipidemic agent, ameliorates the COX deficiency in mice with mutations in COX10, another COX-assembly gene.

Methods

We have investigated the effect of BZF and copper in cells with SCO2 mutations using spectrophotometric methods to analyse respiratory chain activities and a luciferase assay to measure ATP production..

Results

Individual mitochondrial enzymes displayed different responses to BZF. COX activity increased by about 40% above basal levels (both in controls and patients), with SCO2 cells reaching 75-80% COX activity compared to untreated controls. The increase in COX was paralleled by an increase in ATP production. The effect was dose-dependent: it was negligible with 100 ??M BZF, and peaked at 400 ??M BZF. Higher BZF concentrations were associated with a relative decline of COX activity, indicating that the therapeutic range of this drug is very narrow. Combined treatment with 100 ??M CuCl₂ and 200 ??M BZF (which are only marginally effective when administered individually) achieved complete rescue of COX activity in SCO2 cells.

Conclusions

These data are crucial to design therapeutic trials for this otherwise fatal disorder. The additive effect of copper and BZF will allow to employ lower doses of each drug and to reduce their potential toxic effects. The exact mechanism of action of BZF remains to be determined.