Expedition to the missing link: Long noncoding RNAs in cardiovascular diseases.

With the advances in deep sequencing-based transcriptome profiling technology, it is now known that human genome is transcribed more pervasively than previously thought. Up to 90% of the human DNA is transcribed, and a large proportion of the human genome is transcribed as long noncoding RNAs (lncRNAs), a heterogenous group of non-coding transcripts longer than 200 nucleotides. Emerging evidence suggests that lncRNAs are functional and contribute to the complex regulatory networks involved in cardiovascular development and diseases. In this article, we will review recent evidence on the roles of lncRNAs in the biological processes of cardiovascular development and disorders. The potential applications of lncRNAs as biomarkers and targets for therapeutics are also discussed.

Sedation-associated hiccups in adults undergoing gastrointestinal endoscopy and colonoscopy.

AIM: To investigate whether the incidence of hiccups in patients undergoing esophagogastroduodenoscopy (EGD) or same-day bidirectional endoscopy (EGD and colonoscopy; BDE) with sedation is different from those without sedation in terms of quantity, duration and typical onset time. METHODS: Consecutive patients scheduled for elective EGD or same-day BDE at the gastrointestinal endoscopy unit or the health examination center were allocated to two groups: EGD without sedation (Group A) and BDE with sedation (Group B). The use of sedation was based on the patients' request. Anesthesiologists participated in this study by administrating sedative drugs as usual. A single experienced gastroenterologist performed both the EGD and the colonoscopic examinations for all the patients. The incidence, duration and onset time of hiccups were measured in both groups. In addition, the association between clinical variables and hiccups were analyzed. RESULTS: A total of 435 patients were enrolled in the study. The incidences of hiccups in the patients with and without sedation were significantly different (20.5% and 5.1%, respectively). The use of sedation for patients undergoing endoscopy was still significantly associated with an increased risk of hiccups (adjusted odds ratio: 8.79, P < 0.001) after adjustment. The incidence of hiccups in males under sedation was high (67.4%). The sedated patients who received 2 mg midazolam developed hiccups more frequently compared to those receiving 1 mg midazolam (P = 0.0028). The patients with the diagnosis of gastroesophageal reflux disease (GERD) were prone to develop hiccups (P = 0.018). CONCLUSION: Male patients undergoing EGD or BDE with sedation are significantly more likely to suffer from hiccups compared to those without sedation. Midazolam was significantly associated with an increased risk of hiccups. Furthermore, patients with GERD are prone to develop hiccups.

Intramuscular electroporation with the pro-opiomelanocortin gene in rat adjuvant arthritis.

Endogenous opioid peptides have an essential role in the intrinsic modulation and control of inflammatory pain, which could be therapeutically useful. In this study, we established a muscular electroporation method for the gene transfer of pro-opiomelanocortin (POMC) in vivo and investigated its effect on inflammatory pain in a rat model of rheumatoid arthritis. The gene encoding human POMC was inserted into a modified pCMV plasmid, and 0-200 microg of the plasmid-POMC DNA construct was transferred into the tibialis anterior muscle of rats treated with complete Freund's adjuvant (CFA) with or without POMC gene transfer by the electroporation method. The safety and efficiency of the gene transfer was assessed with the following parameters: thermal hyperalgesia, serum adrenocorticotropic hormone (ACTH) and endorphin levels, paw swelling and muscle endorphin levels at 1, 2 and 3 weeks after electroporation. Serum ACTH and endorphin levels of the group into which the gene encoding POMC had been transferred were increased to about 13-14-fold those of the normal control. These levels peaked 1 week after electroporation and significantly decreased 2 weeks after electroporation. Rats that had received the gene encoding POMC had less thermal hypersensitivity and paw swelling than the non-gene-transferred group at days 3, 5 and 7 after injection with CFA. Our promising results showed that transfer of the gene encoding POMC by electroporation is a new and effective method for its expression in vivo, and the analgesic effects of POMC cDNA with electroporation in a rat model of rheumatoid arthritis are reversed by naloxone.

Body Weight-Related ionized hypomagnesemia in pediatric patients undergoing cardiopulmonary bypass for surgical repair of congenital cardiac defects.

STUDY OBJECTIVES: To examine the serial time course of perioperative plasma ionized magnesium (iMg(2+)) concentrations and to analyze the plasma iMg(2+) concentrations in children with different body mass who were undergoing open-heart surgery. DESIGN: Randomized, single-blinded study. SETTING: University-affiliated hospital of an academic medical institution. PATIENTS: 38 children undergoing open-heart surgery. INTERVENTIONS: Patients were divided into three groups according to their body mass: Group 1 (n = 12) <10 kg, Group 2 (n = 13) 10 kg to 20 kg, and Group 3 (n = 13) >20 kg. MEASUREMENTS: The relationship of iMg(2+) among the three groups of different body mass were analyzed at five different time intervals during the operation: induction of anesthesia, 5 minutes and 30 minutes after the onset of cardiopulmonary bypass (CPB), the beginning of rewarming, and the end of surgery. MAIN RESULTS: iMg(2+) levels at 5 minutes after onset of CPB in patients weighing less than 20 kg (Groups 1 and 2) differed with those weighing more than 20 kg (Group 3) (p = 0.007 and 0.013). However, there was no difference in the iMg(2+) levels between Groups 1 and 2 (p = 0.993). In addition, iMg(2+) levels at 5 minutes after onset of bypass correlated well (r(2) = 0.66) in children with body mass less than 20 kg. CONCLUSIONS: Low levels of ionized magnesium is an important finding in patients at the onset of CPB, which correlates well with the body mass of patients weighing less than 20 kg, and could be predicted by the regression curve. Based on these findings, hypomagnesemia can be prevented during CPB.

Inhibition of experimental angiogenesis of cornea by somatostatin.

BACKGROUND: This study evaluated the inhibitory activity of somatostatin 14 on the angiogenesis of cornea in vivo. METHODS: Corneal neovascularization was induced with a pellet containing 90 ng of basic fibroblast growth factor (bFGF) in a rat corneal pocket model. Three kinds of pellets were made containing bFGF plus somatostatin (SST) 0 ng, 20 ng and 200 ng for the control group, group 1 and group 2, respectively. Neovascularization was observed biomicroscopically from day 4 to day 8, and the corneas were then examined for changes in histology. Quantitation of angiogenesis in the cornea was accomplished by caliper and image analysis. RESULTS: The 200-ng dose of SST showed significant inhibition of both length and area of neovascularization on day 7 (0.62+/-0.11 mm vs 1.29+/-0.16 mm, 0.50+/-0.16 mm2 vs 1.35+/-0.29mm2, group 2 vs control; P<0.05). The 20 ng of somatostatin did not demonstrate any significant inhibition of neovascularization compared with the control group. CONCLUSION: Our study demonstrated that SST 14 can reduce bFGF-induced corneal angiogenesis. This shows the potential value of somatostatin in the treatment of corneal neovascularization.

Intrathecal spinal progenitor cell transplantation for the treatment of neuropathic pain.

Injury to, or dysfunction of, the nervous system can lead to spontaneous pain, hyperalgesia, and/or allodynia. It is believed that the number and activity of GABAergic neurons gradually decreases over the dorsal horn. Glutamic acid decarboxylase (GAD) immunocompetence has been demonstrated on spinal progenitor cells (SPCs) cultivated in vitro. The intrathecal implantation of these cultivated progenitor cells may provide a means of alleviating neuropathic pain. Chronic constriction injury (CCI) of the sciatic nerve was used to induce chronic neuropathic pain in the hind paw of rats. SPCs (1 x 10(6)) were implanted intrathecally on the third day after the CCI surgery. The behavioral response to thermal hyperalgesia was observed and recorded during the 14 days postsurgery. Various techniques were utilized to trace the progenitor cells, confirm the differentiation, and identify the neurotransmitters involved. GAD immunoactivity was revealed for 65% of the cultivated spinal progenitor cells in our study. We also determined that transplanted cells could survive more than 3 weeks postintrathecal implantation. Significant reductions were demonstrated for responses to thermal stimuli for the CCI rats that had received intrathecal SPC transplantation. A novel intrathecal delivery with SPCs reduced CCI-induced neuropathic pain.