Hungry bone syndrome after parathyroid surgery.

INTRODUCTION: Data on the incidence rates of hungry bone syndrome after parathyroidectomy in patients on dialysis are inconsistent, as the published rates vary from 15.8% to 92.9%. METHODS: Between 2009 and 2019, 120 hemodialysis patients underwent parathyroidectomy for secondary hyperparathyroidism at the Chang Gung Memorial Hospital. The patients were stratified into two groups based on the presence (n = 100) or absence (n = 20) of hungry bone syndrome after parathyroidectomy. FINDINGS: Subtotal parathyroidectomy was the most common surgery performed (76.7%), followed by total parathyroidectomy with autoimplantation (23.3%). Pathological examination revealed parathyroid hyperplasia. Hungry bone syndrome developed within 0.3 ± 0.3 months and lasted for 11.1 ± 14.7 months. After surgery, compared with patients without hungry bone syndrome, patients with hungry bone syndrome had lower levels of nadir corrected calcium (P < 0.001), as well as lower nadir (P < 0.001) and peak (P < 0.001) intact parathyroid hormone levels. During 59.3 ± 44.0 months of follow-up, persistence and recurrence of hyperparathyroidism occurred in 25 (20.8%) and 30 (25.0%) patients, respectively. Furthermore, patients with hungry bone syndrome had a lower rate of persistent hyperparathyroidism than those without hungry bone syndrome (P < 0.001). Four patients (3.3%) underwent a second parathyroidectomy. Patients with hungry bone syndrome received fewer second parathyroidectomies than those without hungry bone syndrome (P < 0.001). Finally, a multivariate logistic regression model revealed that the preoperative blood ferritin level was a negative predictor of the development of hungry bone syndrome (P = 0.038). DISCUSSION: Hungry bone syndrome is common (83.3%) after parathyroidectomy for secondary hyperparathyroidism in patients undergoing hemodialysis, and this complication should be monitored and managed appropriately.

Intra-Articular Injection of (-)-Epigallocatechin 3-Gallate (EGCG) Ameliorates Cartilage Degeneration in Guinea Pigs with Spontaneous Osteoarthritis.

Osteoarthritis (OA) is the most prevalent joint disease that causes an enormous burden of disease worldwide. (-)-Epigallocatechin 3-gallate (EGCG) has been reported to reduce post-traumatic OA progression through its anti-inflammatory property. Aging is the most crucial risk factor of OA, and the majority of OA incidences are related to age and not trauma. In this study, we assess whether EGCG can ameliorate cartilage degradation in primary OA. In an in-vitro study, real-time PCR was performed to assess the expression of genes associated with human articular chondrocyte homeostasis. A spontaneously occurring OA model in guinea pigs was used to investigate the effect of EGCG in vivo. OA severity was evaluated using Safranin O staining and Osteoarthritis Research Society International (OARSI) scores, as well as by immunohistochemical (IHC) analysis to determine the protein level of type II collagen (Col II), matrix metalloproteinase 13 (MMP-13), and p16 ink4a in articular cartilage. In the in-vitro study, EGCG increased the gene expression of aggrecan and Col II and decreased the expression of interleukin-1, cyclooxygenase 2, MMP-13, alkaline phosphatase, Col X, and p16 Ink4a; EGCG treatment also attenuated the degraded cartilage with a lower OARSI score. Meanwhile, IHC results showed that EGCG exerted an anti-OA effect by reducing ECM degradation, cartilage inflammation, and cell senescence with a less-immunostained Col II, MMP-13, and p16 Ink4a. In conclusion, these findings suggest that EGCG may be a potential disease-modifying OA drug for the treatment of primary OA.

Synthesis and evaluation of 2-(2'-((dimethylamino)methyl)-4'-(2-fluoroethoxy-substituted)phenylthio)benzenamine derivatives as potential positron emission tomography imaging agents for serotonin transporters.

A series of diphenylsulfide derivatives with various substitutions at the 4-position on phenyl ring A and different lengths of the 2-fluoroethoxy-substituted side-chain at the 4'-position on ring B were synthesized and evaluated as potential positron emission tomography (PET) imaging agents for serotonin transporters (SERT). These ligands exhibited high SERT binding affinities (Ki = 0.11-1.3 nM) and the 4-methyl-substituted (4-Me) compounds 7a and 8a displayed excellent selectivity for SERT versus norepinephrine transporters (NET) (392- and 700-fold, respectively). In the parallel artificial membrane permeability assay (PAMPA), these ligands demonstrated moderate to high brain penetration, and the 4-Me analogs showed higher BBB permeability than the corresponding 4-F analogs. The 2-fluoroethoxy-substituted ligands showed higher metabolic stability and lower lipophilicity than 4-F-ADAM. [18F]7a-c were readily prepared using an automatic synthesizer and exhibited significant uptake and slow washout in rat brains. At 120 min after iv injection, [18F]7a exhibited the highest uptake in the midbrain, whereas [18F]7b exhibited the highest uptake in the hypothalamus and midbrain. After treatment with citalopram, a SERT-selective ligand, the uptake of [18F]7a in the hypothalamus and striatum was significantly decreased. The potent and highly selective SERT binding and the selective and reversible accumulation in SERT-rich brain regions suggested that [18F]7a is a promising lead for the further development of novel [18F]-labeled PET imaging agents for SERT binding sites in the brain.

Sesamin, a Naturally Occurring Lignan, Inhibits Ligand-Induced Lipogenesis through Interaction with Liver X Receptor Alpha (LXRα) and Pregnane X Receptor (PXR).

Liver X receptor (LXR) is a nuclear receptor that regulates various biological processes, including de novo lipogenesis, cholesterol metabolism, and inflammation. Selective inhibition of LXR may aid the treatment of nonalcoholic fatty liver disease (NAFLD). Sesamin is a naturally occurring lignan in many dietary plants and has a wide range of beneficial effects on metabolism. The mechanism underlying sesamin action especially on the regulation of LXR remains elusive. Reporter assays, mRNA and protein expression, and in silico modeling were used to identify sesamin as an antagonist of LXRα. Sesamin was applied to the hepatic HepaRG and intestinal LS174T cells and showed that it markedly ameliorated lipid accumulation in the HepaRG cells, by reducing LXRα transactivation, inhibiting the expression of downstream target genes. This effect was associated with the stimulation of AMP-activated protein kinase (AMPK) signaling pathway, followed by decreased T0901317-LXRα-induced expression of SREBP-1c and its downstream target genes. Mechanistically, sesamin reduced the recruitment of SRC-1 but enhanced that of SMILE to the SREBP-1c promoter region under T0901317 treatment. It regulated the transcriptional control exerted by LXRα by influencing its interaction with coregulators and thus decreased mRNA and protein levels of genes downstream of LXRα and reduced lipid accumulation in hepatic cells. Additionally, sesamin reduced valproate- and rifampin-induced LXRα and pregnane X receptor (PXR) transactivation. This was associated with reduced expression of target genes and decreased lipid accumulation. Thus, sesamin is an antagonist of LXRα and PXR and suggests that it may alleviate drug-induced lipogenesis via the suppression of LXRα and PXR signaling.

Oleanolic Acid Inhibits Liver X Receptor Alpha and Pregnane X Receptor to Attenuate Ligand-Induced Lipogenesis.

Liver X receptor α (LXRα) controls important biological and pathophysiological processes such as lipid homeostasis. Inhibiting LXRα transactivation may beneficial in the treatment of nonalcoholic fatty liver disease (NAFLD), which is one of the main causes of liver diseases and hyperlipidemia. Oleanolic acid (OA) is a naturally occurring triterpenoid found in many plants. It has several beneficial effects on biological pathways; however, the mechanisms underlying its effects on LXRα are unclear. Therefore, we evaluated the effects of OA on T0901317-induced LXRα activation and explored whether OA can attenuate hepatic lipogenesis. The results showed that OA significantly decreased the promoter activities of LXR response element and sterol regulatory element binding protein-1c (SREBP-1c). It also decreased the mRNA and protein expression of LXRα target genes. These resulted in reduced hepatocellular lipid content. Our results also revealed that the overall binding pose of OA is similar to the X-ray pose of T0901317. Furthermore, OA stimulated AMP-activated protein kinase phosphorylation in hepatic cells. Additionally, it increased small heterodimer partner-interacting leucine zipper protein (SMILE) but decreased steroid receptor coactivator-1 (SRC-1) recruitment to the SREBP-1c promoter region. OA also enhanced LXRα-mediated induction of reverse cholesterol transport (RCT)-related gene, ATP-binding cassette transporter (ABC) A1, and ABCG1 expression in intestinal cells. It was found that OA increased the binding of SRC-1 but decreased SMILE recruitment to the ABCG1 gene promoter region. Furthermore, it reduced valproate- and rifampin-induced LXRα- and pregnane X receptor-mediated lipogenesis, respectively, which indicates its potential benefit in treating drug-induced hepatic steatosis. The results also show that OA is liver-specific and can be selectively repressed of lipogenesis. Moreover, it preserves and enhances LXRα-induced RCT stimulation. The results show that OA may be a promising treatment for NAFLD. Additionally, it can be used in the development of LXRα agonists to prevent atherosclerosis.

Effects of antiepileptic drugs on lipogenic gene regulation and hyperlipidemia risk in Taiwan: a nationwide population-based cohort study and supporting in vitro studies.

To characterize the association between epilepsy, use of antiepileptic drugs (AEDs), and the risk of hyperlipidemia, we conducted a nationwide population-based cohort study with data obtained from the National Health Insurance Research Database of Taiwan. The effects of AEDs on lipogenic gene expression were also examined in vitro. We identified 3617 cases involving patients, whose epilepsy was newly diagnosed between 2000 and 2011, and selected a comparison cohort comprising 14,468 patients without epilepsy. The Cox proportional hazards model was used to evaluate the association between epilepsy, AED use, and hyperlipidemia. The incidence rate of hyperlipidemia was higher in the epilepsy cohort than in the comparison cohort, with an adjusted hazard ratio (aHR) of 1.21 [95% confidence interval (CI): 1.06-1.38] after adjusting for comorbidities and medications. Epilepsy patients not taking AEDs had a higher risk of hyperlipidemia (aHR 1.65; 95% CI 1.35-2.03). Among AEDs, only valproate treatment showed a higher risk of hyperlipidemia (aHR 1.53; 95% CI 1.01-2.33), although the dose-dependent effect did not reach statistical significance. In vitro studies with two hepatic cell lines showed that valproate may exert its effects by activating the liver X receptor alpha (LXRα) signaling pathway, inducing the expression of lipogenesis-related genes and increasing cellular lipid contents. In silico calculations concluded that valproate can bind stably with the ligand-binding domain of LXRα. Thus, valproate-induced hepatic lipogenic gene expression may occur through LXRα activation. Predicting the 'off-target' effects of valproate may prove valuable in developing antiepileptic agents with fewer adverse reactions. Monitoring blood lipid levels throughout the course of treatment is recommended.

Association of Antituberculosis Treatment and Lower Risk of Hyperlipidemia in Taiwanese Patients: A Population-Based Case-Control Study.

The association between anti-tuberculosis (TB) treatments and the risk of developing hyperlipidemia remains unclear. Data were obtained from the Longitudinal Health Insurance Database 2000 (LHID2000). The case group included patients newly diagnosed with hyperlipidemia (n=16,054) between 2006 and 2011 selected from the LHID2000. A four-fold number of hyperlipidemia-free cases (n=64,216) were matched with case patients by age, sex, and index year to create the control group. Univariable and multivariable unconditional logistic regression analyses were conducted to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the association between hyperlipidemia and anti-TB medication use. Patients that used isoniazid (INH) were significantly associated with a decreased risk of hyperlipidemia (OR=0.71, 95%CI=0.57-0.88). After adjustment for age, sex, urbanization level, and income as well as ethambutol, pyrazinamide, streptomycin, and anti-human immunodeficiency virus drug medications, a dose-dependent risk of hyperlipidemia was observed in the INH, rifampin (RIF), and INH and RIF groups with the ORs progressively decreasing as the cumulative dose increased. In the Taiwanese patients who used anti-TB medications, INH and RIF use was associated with a decreased risk of hyperlipidemia.

Biochanin a, a phytoestrogenic isoflavone with selective inhibition of phosphodiesterase 4, suppresses ovalbumin-induced airway hyperresponsiveness.

The present study investigated the potential of biochanin A, a phytoestrogenic isoflavone of red clover (Triflolium pratense), for use in treating asthma or chronic obstructive pulmonary disease (COPD). Biochanin A (100 µmol/kg, orally (p.o.)) significantly attenuated airway resistance (R(L)), enhanced pause (P(enh)), and increased lung dynamic compliance (C(dyn)) values induced by methacholine (MCh) in sensitized and challenged mice. It also significantly suppressed an increase in the number of total inflammatory cells, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, and tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid (BALF) of the mice. However, it did not influence interferon (IFN)-γ levels. Biochanin A (100 µmol/kg, p.o.) also significantly suppressed the total and ovalbumin (OVA)-specific immunoglobulin E (IgE) levels in the serum and BALF, and enhanced the total IgG(2a) level in the serum of these mice. The PDE4(H)/PDE4(L) value of biochanin A was calculated as >35. Biochanin A did not influence xylazine/ketamine-induced anesthesia. Biochanin A (10~30 µM) significantly reduced cumulative OVA (10~100 µg/mL)-induced contractions in the isolated guinea pig trachealis, suggesting that it inhibits degranulation of mast cells. In conclusion, red clover containing biochanin A has the potential for treating allergic asthma and COPD.

Ayanin, a non-selective phosphodiesterase 1-4 inhibitor, effectively suppresses ovalbumin-induced airway hyperresponsiveness without affecting xylazine/ketamine-induced anesthesia.

In recent in vitro reports, the IC(50) value of ayanin (quercetin-3,7,4'-O-trimethylether) was 2.2microM for inhibiting interleukin (IL)-4 production from purified basophils, and its therapeutic ratio was >19. Therefore, we were interested in investigating the effects on ovalbumin induced airway hyperresponsiveness in vivo, and to clarify its potential for treating asthma. Ayanin (30-100micromol/kg, orally (p.o.)) dose-dependently and significantly attenuated the enhanced pause (P(enh)) value induced by methacholine in sensitized and challenged mice. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including IL-2, IL-4, IL-5, and tumor necrosis factor (TNF)-alpha in bronchoalveolar lavage fluid of these mice. However, at 100micromol/kg, it significantly enhanced the level of interferon (IFN)-gamma. In addition, ayanin (30-100micromol/kg, p.o.) dose-dependently and significantly suppressed total and OVA-specific immunoglobulin (Ig)E levels in the serum and bronchoalveolar lavage fluid, and enhanced the IgG(2a) level in serum of these mice. In the present results, ayanin did not affect xylazine/ketamine-induced anesthesia, suggesting that ayanin has few or no adverse effects, such as nausea, vomiting, and gastric hypersecretion. In conclusion, the above results suggest that ayanin may have the potential for use in treating allergic asthma.

An open-label, randomized, active-controlled equivalent trial of osmotic release oral system methylphenidate in children with attention-deficit/hyperactivity disorder in Taiwan.

This study examined the efficacy and safety of osmotic release oral system methylphenidate (OROS MPH) as compared with immediate-release MPH (IR MPH) in children with attention-deficit/hyperactivity disorder (ADHD) in Taiwan. Sixty-four children with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) ADHD, ages 6-15 years, were randomized to OROS MPH once daily (n = 32) and IR MPH three times daily (n = 32) in an open, randomized, active-controlled equivalent 28-day trial. The main outcome measures included the Conner's Teacher Rating Scale -Revised: Short Form and Conner's Parent Rating Scale-Revised: Short Form, and other measures of social adjustment and side effects. Results showed significant reductions in the core ADHD symptoms, which did not differ between the two treatment groups. Compared to the IR MPH group, the OROS MPH group showed a significantly greater slope of reductions in ADHD symptoms and decline in the severity of problems at school, and with peers and parents over time. There was no difference in rates of side effect profile between the two groups. Our findings suggest that OROS MPH is superior over IR MPH in the greater magnitude of improvement over study period without increased side effects in the Chinese population.

Determinants of adherence to methylphenidate and the impact of poor adherence on maternal and family measures.

OBJECTIVE: The aim of this study was to examine the association between adherence to immediate-release methylphenidate (IR MPH) and maternal psychological distress, parenting style, parent- child relationship, and perceived family support. METHODS: The sample consisted of 307 children with attention-deficit hyperactivity disorder (ADHD) (271 boys and 36 girls), 6-17 years of age, who had been treated with IR MPH for the past 6 months. The measures included the Chinese Health Questionnaire, Parental Bonding Instrument, Family APGAR, and Home Behaviors of the Social Adjustment Inventory for Children and Adolescents. RESULTS: Reasons for poor adherence (n = 79; 25.7%) included forgetting medication (72.7%), the medication having no effect (20.0%), and refusing medication (12.7%). Increased age and three-times-daily administration were the major predictors for poor adherence to IR MPH. Poor adherence was associated with increased degree of maternal psychological distress, indifferent parenting, maternal overprotection/control, poor family support, decreased interaction with parents, and increased problems at home. CONCLUSIONS: Findings indicate that multiple daily dosing of MPH increases the likelihood of poor adherence, particularly in adolescents, and that poor adherence is associated with impaired maternal/family process. Once-daily administration of MPH is necessary to improve adherence and to decrease the possible exacerbation of tense parent-child relationships caused by poor drug adherence.