Repeated vertebral compression fractures in young adult may imply functional adrenal tumor.

BACKGROUND: Patients with adrenal Cushing's syndrome (ACS) typically present with central obesity, hirsutism, hypertension, or glucose intolerance, which can be easily identified by a clinical physician. However, recognizing those with subclinical CS or those with less common symptoms and signs is challenging to the subspecialist, which can lead to delayed diagnosis and treatment. We report a case who presented with repeated vertebral fractures in 6 months. Typical physical appearance of CS was not shown so that suspicions were not raised until severe osteoporosis was demonstrated from bone marrow density study. From our case report, endocrine tests and image survey should always be considered in young patients with repeat vertebral fractures. CASE PRESENTATION: A 48-year-old man presented with severe back pain for 3 months. Second and fifth lumbar spine (L2 and L5) vertebral compression fractures were noted from X-ray and magnetic resonance imaging (MRI), and vertebroplasty was performed by orthopedic surgeons. After 1 month, a newly developed compression fracture of the ninth to twelfth thoracic spine and L4-L5 were noted. Severe osteoporosis was noted from the hip bone mineral density test, and he was referred to an endocrinologist for analysis. Serial endocrine tests confirmed hypercortisolism, and subsequent abdomen MRI showed a left adrenal tumor. ACS was diagnosed. Left laparoscopic adrenalectomy was performed, and the patient received cortisol supplement for 12 months. Thereafter, no new fractures were identified. CONCLUSIONS: ACS should be considered and carefully verified in middle-aged adults who present with severe osteoporosis and repeated vertebral compression fracture.

Literature Review and Meta-Analysis of Transcutaneous Electrical Nerve Stimulation in Treating Chronic Back Pain.

BACKGROUND AND OBJECTIVES: This study is a meta-analysis of randomized controlled trials comparing the efficacy of transcutaneous electrical nerve stimulation (TENS) to a control and to other nerve stimulation therapies (NSTs) for the treatment of chronic back pain. METHODS: Citations were identified in MEDLINE, the Cochrane Library, Google Scholar, and ClinicalTrials.gov through June 2014 using the following keywords: nerve stimulation therapy, transcutaneous electrical nerve stimulation, back pain, chronic pain. Control treatments included sham, placebo, or medication only. Other NSTs included electroacupuncture, percutaneous electrical nerve stimulation, and percutaneous neuromodulation therapy. RESULTS: Twelve randomized controlled trials including 700 patients were included in the analysis. The efficacy of TENS was similar to that of control treatment for providing pain relief (standardized difference in means [SDM] = -0.20; 95% confidence interval [CI], -0.58 to 0.18; P = 0.293). Other types of NSTs were more effective than TENS in providing pain relief (SDM = 0.86; 95% CI, 0.15-1.57; P = 0.017). Transcutaneous electrical nerve stimulation was more effective than control treatment in improving functional disability only in patients with follow-up of less than 6 weeks (SDM = -1.24; 95% CI, -1.83 to -0.65; P < 0.001). There was no difference in functional disability outcomes between TENS and other NSTs. CONCLUSIONS: These results suggest that TENS does not improve symptoms of lower back pain, but may offer short-term improvement of functional disability.

Development and characterization of docetaxel-loaded lecithin-stabilized micellar drug delivery system (LsbMDDs) for improving the therapeutic efficacy and reducing systemic toxicity.

In the present study, we attempted to develop a lecithin-stabilized micellar drug delivery system (LsbMDDs) for loading docetaxel (DTX) to enhance its therapeutic efficacy and minimize systemic toxicity. A novel DTX-loaded LsbMDDs was optimally prepared by a thin-film hydration method and then hydrated with a lecithin nanosuspension while being subjected to ultrasonication. Physical characteristics of the optimized DTX-loaded LsbMDDs formulations were examined and found to have a mean size of <200 nm, an encapsulation efficiency of >90%, and drug loading of >6% with stability at room temperature and at 4 °C being longer than 2 and 7 days, respectively. The in vitro release of DTX from the DTX-loaded LsbMDDs was slower than that from the generic product of DTX (Tynen®). A cell viability assay demonstrated that the LsbMDDs showed better cytotoxicity than Tynen® against CT26 cancer cells. The in vivo antitumor efficacy of the DTX-loaded LsbMDDs was observed to be better than that of Tynen® in a CT26 tumor-bearing mice model. A high-dose regimen of the DTX-loaded LsbMDDs formulation showed greater inhibition of DU145 tumor growth than did Tynen®, but with less to similar systemic toxicity. An in vivo study also showed that a greater amount of drug was able to accumulate in the tumor site with the DTX-loaded LsbMDDs, and its maximal tolerable doses for single and repeated injections were 2-2.5-fold higher than those of Tynen®. In conclusion, the LsbMDDs could be a promising high drug-loaded nanocarrier for delivering hydrophobic chemotherapeutic agents that can enhance the efficacy of chemotherapy and reduce systemic toxicity.

Natural phosphodiesterase-4 inhibitors from the leaf skin of Aloe barbadensis Miller.

The ethanolic extract of Aloe barbadensis Miller leaf skin showed inhibitory activity against phosphodiesterase-4D (PDE4D), which is a therapeutic target of inflammatory disease. Subsequent bioassay-guided fractionation led to the isolation of two new anthrones, 6'-O-acetyl-aloin B (9) and 6'-O-acetyl-aloin A (11), one new chromone, aloeresin K (8), together with thirteen known compounds. Their chemical structures were elucidated by spectroscopic methods including UV, IR, 1D and 2D NMR, and HRMS. All of the isolates were screened for their inhibitory activity against PDE4D using tritium-labeled adenosine 3',5'-cyclic monophosphate ((3)H-cAMP) as substrate. Compounds 13 and 14 were identified as PDE4D inhibitors, with their IC50 values of 9.25 and 4.42 µM, respectively. These achievements can provide evidences for the use of A. barbadensis leaf skin as functional feed additives for anti-inflammatory purpose.

Natural phosphodiesterase-4 (PDE4) inhibitors from Crotalaria ferruginea.

Bioassay-guided fractionation of the ethanol extract of the Chinese folk medicine Crotalaria ferruginea led to the isolation of a new isoflavonoid, 4'-hydroxy-2'-methylalpinum-isoflavone (1), and eight known analogs (2-9). Their structures were elucidated by spectroscopic analysis. Compounds 1, 2, 5, and 8 showed inhibitory activities against phosphodiesterase-4 (PDE4), a therapeutic target of asthma, with IC50 values ranging from 2.57 to 8.94 µM. The possible action mechanism and the structure-activity relationship (SAR) of the active isoflavonoids were explored by using molecular docking and molecular dynamics (MD) simulation methods. Our study herein may explain the anti-inflammatory function of this plant in Chinese folk medicine.

Prenylated coumarins: natural phosphodiesterase-4 inhibitors from Toddalia asiatica.

Bioassay-guided fractionation of the ethanolic extract of the roots of Toddalia asiatica led to the isolation of seven new prenylated coumarins (1-7) and 14 known analogues (8-21). The structures of 1-7 were elucidated by spectroscopic analysis, and their absolute configurations were determined by combined chemical methods and chiral separation analysis. Compounds 1-5, named toddalin A, 3‴-O-demethyltoddalin A, and toddalins B-D, represent an unusual group of phenylpropenoic acid-coupled prenylated coumarins. Compounds 1-21 and four modified analogues, 10a, 11a, 13a, and 17a, were screened by using tritium-labeled adenosine 3',5'-cyclic monophosphate ([3H]-cAMP) as substrate for their inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 3, 8, 10, 10a, 11, 11a, 12, 13, 17, and 21 exhibited inhibition with IC50 values less than 10 µM. Toddacoumalone (8), the most active compound (IC50=0.14 µM), was more active than the positive control, rolipram (IC50=0.59 µM). In addition, the structure-activity relationship and possible inhibitory mechanism of the active compounds are also discussed.

MEMS microwell and microcolumn arrays: novel methods for high-throughput cell-based assays.

Although the cell-based assay is becoming more popular for high throughput drug screening and the functional characterization of disease-associated genes, most researchers in these areas do not use it because it is a complex and expensive process. We wanted to create a simple method of performing an on-chip cell-based assay. To do this, we used micro-electro-mechanical systems (MEMS) to fabricate a microwell array chip comprised of a glass substrate covered with a photoresist film patterned to form multiple microwells and tested it in two reverse transfection experiments, an exogenous gene expression study and an endogenous gene knockdown study. It was used effectively in both. Then, using the same MEMS technology, we fabricated a complementary microcolumn array to be used as a drug carrier device to topically apply drugs to cells cultured in the microwell array. We tested the effectiveness of microwell-microcolumn on-chip cell-based assay by using it in experiments to identify epidermal growth factor receptor (EGFR) activity inhibitors, for which it was found to provide effective high throughput and high content functional screening. In conclusion, this new method of cell-based screening proved to be a simple and efficient method of characterizing gene function and discovering drug leads.