The Anabolic Effect of Teriparatide is Undermined by Low Levels of High-Density Lipoprotein Cholesterol

Intermittent parathyroid hormone (PTH) administration has a potent ability to increase bone mass, regardless of underlying conditions or species. A recent study using LDLR ^?/? mice showed that the anabolic effect of PTH was blunted by hyperlipidemia, whereas PTH anabolism was rescued by enhancement of high-density lipoprotein cholesterol (HDL-C) function. We conducted a retrospective longitudinal study to determine whether lipid profiles also affect the anabolic effect of intermittent PTH treatment in humans. Fifty-two patients (8 males and 44 females, ages 38–85 years) with severe osteoporosis who had been treated with teriparatide (TPTD, recombinant human PTH(1–34) for 12 months were studied at Severance Hospital, Yonsei University. C-telopeptide (CTX) and osteocalcin (OCN) were measured at 0, 3, and 12 months; and total cholesterol, triglycerides, and HDL-C were measured at baseline. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at 0 and 12 months. Lumbar spine BMD increased significantly after 12 months of treatment with TPTD (10.0 ± 9.3 %, p < 0.001). Initial 3-month changes in CTX and OCN levels revealed positive correlations with the increase in lumbar BMD (r = 0.546, p = 0.001 and r = 0.500, p = 0.006, respectively). Moreover, percentage change in lumbar BMD at 12 months showed a negative correlation with baseline total cholesterol (r = ?0.438, p = 0.009) and a positive correlation with HDL-C (r = 0.498, p = 0.016). A smaller 3-month increase in OCN and a lower HDL-C level at baseline were associated with a smaller lumbar BMD increase after TPTD treatment, even after adjustment for age, sex, and other confounding factors (β = 0.462, p = 0.031 for ΔOCN and β = 0.670, p = 0.004 for HDL-C). Plasma levels of lipids, especially HDL-C, seem to be associated with the extent of osteoanabolic effects of TPTD in humans.     

Correlation Between Fluid–Fluid Levels on Initial MRI and the Response to Chemotherapy in Stage IIB Osteosarcoma

Background

The presence of fluid–fluid levels (FFLs) on osteosarcoma magnetic resonance imaging (MRI) is underestimated as a nonspecific finding; however, we hypothesized that FFL in conventional osteosarcoma may be indicative of chemoresistance.

Methods

In 567 stage IIB osteosarcoma patients, we evaluated the following: the incidence of FFL and their correlation with other clinicopathological variables; tumor volume change after chemotherapy and survival according to the presence of FFL; and the relationship between survival and the extent of FFL.

Results

One hundred eight (19 %) tumors showed FFL on initial MRI. FFL were correlated with proximal humeral location (P = 0.017), osteolytic on plain radiographs (P < 0.001), tumor enlargement after chemotherapy (P < 0.001), and poor histological response (P = 0.005). Large tumor (P < 0.01), proximal tumor location (P = 0.01), and presence of FFL (P < 0.01) were independent predictors of poor survival. Compared to the extensive FFL (more than one third of the tumor), small foci of FFL (less than one third of the tumor) showed a high tendency for tumor enlargement after chemotherapy (P < 0.001), poor histologic response (P = 0.001), and worse survival (P < 0.001).

Conclusions

FFL on initial MRI could predict tumor progression after chemotherapy. Notably, tumors with small foci of FFL (less than one third of the tumor) have a high propensity for poor outcome. Patients with this finding should be considered for risk-adapted therapy.     

Differential regulation of observational fear and neural oscillations by serotonin and dopamine in the mouse anterior cingulate cortex

Rationale

The aberrant regulation of serotonin (5-HT) and dopamine (DA) in the brain has been implicated in neuropsychiatric disorders associated with marked impairments in empathy, such as schizophrenia and autism. Many psychiatric drugs bind to both types of receptors, and the anterior cingulate cortex (ACC) is known to be centrally involved with empathy. However, the relationship between the 5-HT/DA system in the ACC and empathic behavior is not yet well known.

Objectives

We investigated the role of 5-HT/DA in empathy-like behavior and in the regulation of ACC neural activity.

Methods

An observational fear learning task was conducted following microinjections of 5-HT, DA, 5-HT and DA, methysergide (5-HT receptor antagonist), SCH-23390 (DA D₁ receptor antagonist), or haloperidol (DA D₂ receptor antagonist) into the mouse ACC. The ACC neural activity influenced by 5-HT and DA was electrophysiologically characterized in vitro and in vivo.

Results

The microinjection of haloperidol, but not methysergide or SCH-23390, decreased the fear response of observing mice. The administration of 5-HT and 5-HT and DA together, but not DA alone, reduced the freezing response of observing mice. 5-HT enhanced delta-band activity and reduced alpha- and gamma-band activities in the ACC, whereas DA reduced only alpha-band activity. Based on entropy, reduced complexity of ACC neural activity was observed with 5-HT treatment.

Conclusions

The current results demonstrated that DA D₂ receptors in the ACC are required for observational fear learning, whereas increased 5-HT levels disrupt observational fear and alter the regularity of ACC neural oscillations.     

Homoegonol attenuates the asthmatic responses induced by ovalbumin challenge

Homoegonol is a lignan derived from styraxlignolide A, which was isolated from Styrax japonica, a medicinal plant widely used for treatment of inflammatory diseases in Korea. We investigated the efficacy of homoegonol for the treatment of allergic asthma using an ovalbumin (OVA)-induced murine asthma model. The mice were sensitized through intraperitoneal injections of OVA on days 0 and 14. On days 21, 22 and 23 after the initial OVA sensitization, the mice were received OVA airway challenge. Homoegonol was administered by oral gavage at a dose of 30 mg/kg 1 h prior to the OVA challenge. The homoegonol-treated mice exhibited reduced inflammatory cell counts and Th2 cytokines in BALF, AHR, and IgE in the serum compared with the OVA-sensitized/challenged mice. The histological analysis of the lung tissue revealed that the administration of homoegonol attenuated the airway inflammation and the mucus overproduction in airway epithelial lesions induced by OVA through a reduction in expression of inducible nitric oxide synthase and matrix metalloproteinase-9. These findings indicate that homoegonol effectively suppresses the asthmatic responses induced by OVA challenge and suggests that homoegonol exhibits potential as therapeutic drug for allergic asthma.     

Effect of a 12-week weight management program on the clinical characteristics and dietary intake of the young obese and the contributing factors to the successful weight loss

BACKGROUND/OBJECTIVES

The objectives were to investigate the effect of a 12-wk intervention with behavioral modification on clinical characteristics and dietary intakes of young and otherwise healthy obese and to identify factors for successful weight loss. The goal was to lose 0.5 kg per week by reducing 300-500 kcal/day and by increasing physical activities.

SUBJECTS AND METHODS

Forty four obese subjects (BMI > 25) and 19 normal weight subjects (BMI 18.5-23) finished the 12-week intervention. Obese subjects participated in 5 group educations and 6 individual counseling sessions. Normal weight subjects attended 6 individual counseling sessions for evaluations of dietary intake and exercise pattern. Anthropometric and clinical characteristics and 3-day dietary records were evaluated at baseline and week12.

RESULTS

Weight and serum triglyceride and free fatty acid concentrations in obese group decreased significantly with intervention. Intakes of energy, fat, and cholesterol decreased significantly in the obese. Active participation, realistic weight loss goal setting, and weight gain after high school graduation not during childhood were identified as key factors for successful weight loss.

CONCLUSIONS

The 12-week intervention with behavioral modification resulted in reduced energy and fat intakes and led to significant weight loss and improvements of clinical characteristics in the obese. The finding that those who became obese during childhood lost less weight indicates the importance of ''early'' intervention.