Mechanism of anti-inflammatory activity of umbelliferone 6-carboxylic acid isolated from Angelica decursiva

Aims of the study

We recently reported the potential antioxidant and anti-inflammatory activities of umbelliferone 6-carboxylic acid (UMC) isolated from the whole plants of Angelica decursiva. In this study, we elucidated the anti-inflammatory mechanisms of UMC in vitro and in vivo.

Methods

The inhibitory effects of UMC on the production of nitric oxide (NO), prostaglandin E₂ (PGE₂), and tumor necrosis factor-α (TNF-α), the expression of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the activation of nuclear factor kappa B (NF-κB) were evaluated using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The reactive oxygen species (ROS) generation inhibitory activity of UMC was evaluated using t-butyl hydroperoxide (t-BHP)-induced RAW 264.7 cells. Furthermore, the in vivo anti-inflammatory activity of UMC was evaluated using carrageenan induced mouse paw edema model.

Results

UMC dose-dependently inhibited NO and PGE₂ production by down-regulating iNOS and COX-2 protein expression in LPS-stimulated RAW 264.7 macrophages. UMC also suppressed the production of the proinflammatory cytokine TNF-α in LPS stimulated RAW 264.7 cells in a concentration dependent manner. In addition, UMC dose-dependently prevented LPS-induced nuclear translocation of NF-κB in RAW 264.7 macrophages. Furthermore, UMC exhibited the inhibitory activity against t-BHP-induced ROS generation in RAW 264.7 cells with an IC₅₀ value of 705.1 μg/ml. Moreover, UMC inhibited λ-carrageenan induced mouse paw edema by 70.40 and 60.20% at doses of 50 and 25 mg/kg body weight, respectively.

Conclusion

The combined results of this study indicate that UMC is an important anti-inflammatory constituent of A. decursiva and its anti-inflammatory effect was due to its ability to inhibit the production of inflammatory mediators via inhibition of NF-κB activation pathway.     

Surgical Outcomes of Canalicular Trephination Combined with Endoscopic Dacryocystorhinostomy in Patients with Distal or Common Canalicular Obstruction

PurposeThis study investigated the surgical outcomes of canalicular trephination combined with endoscopic dacryocystorhinostomy (DCR) in patients with a distal or common canalicular obstruction. It also identified the factors affecting surgical success rates associated with this technique.MethodsWe retrospectively reviewed the medical records of 57 patients (59 eyes) in whom a canalicular obstruction was encountered during endoscopic DCR. All patients were treated with endoscopic DCR, followed by canalicular trephination and silicone tube placement. The surgical outcome was categorized as a functional success according to the patient''s subjective assessment of symptoms, including epiphora, and as an anatomical success according to a postoperative nasolacrimal duct irrigation test. Surgical success rates were compared based on age, sex, location of the obstruction, number of silicone tubes, and experience of the surgeon.ResultsFunctional success was achieved in 55 of 59 eyes (93%) at one month, 50 eyes (84%) at three months, and 46 eyes (78%) at six months. Anatomical success was achieved in 58 of 59 eyes (98%) at one month, 52 eyes (88%) at three months, and 50 eyes (84%) at six months. There was a statistically significant difference in surgical outcome according to the experience of the surgeon. The anatomical success rate at the six-month follow-up exam was 95.4% in the >5 years of experience group, and 53.3% in the <5 years of experience group (p = 0.008, Pearson chi-square test).ConclusionsThe success rate of canalicular trephination combined with endoscopic DCR in patients with a distal or common canalicular obstruction decreased gradually during the six-month follow-up period. In particular, patients undergoing procedures with experienced surgeons tended to show excellent surgical outcomes at the six-month follow-up exam.     

Efficacy of lamivudine re-treatment for relapsed patients after an initial lamivudine therapy in HBeAg-positive chronic hepatitis B

The efficacy of lamivudine re-treatment in chronic hepatitis B (CHB) patients who relapse after HBeAg seroconversion with lamivudine has not been investigated. The aim of this study was to evaluate the efficacy of lamivudine re-treatment in relapsed patients. Among 192 patients who had achieved HBeAg seroconversion with lamivudine at a dose of 100 mg/day, 121 patients discontinued lamivudine. Relapse occurred in 49 patients (40.5%). Thirty-three relapsed patients received lamivudine re-treatment for at least 6 months. The mean duration of lamivudine re-treatment was 16 months and the follow-up period was 8.9 months. HBeAg seroconversion was achieved in 23 patients (69.7%). The cumulative HBeAg seroconversion rates at 5, 9, and 12 months were 60, 64, and 67%, respectively. The mean time to HBeAg seroconversion in lamivudine re-treatment was shorter than that in the initial therapy (4.7 months vs. 9.7 months). Viral breakthrough occurred in six (18.2%) patients. All patients with viral breakthrough were accompanied by elevation of serum alanine aminotransferase (ALT) levels. Among 15 patients who discontinued lamivudine re-treatment after HBeAg seroconversion, relapse occurred in six patients (40%). All relapses occurred within 9 months after the discontinuation of lamivudine re-treatment. In conclusion, lamivudine re-treatment in relapsed patients after initial lamivudine therapy had a higher response rate and shorter duration to HBeAg seroconversion than during the initial therapy. However, HBeAg seroconversion induced by lamivudine re-treatment was not durable.     

Variation in intraocular pressure caused by repetitive positional changes during laparoscopic colorectal surgery: a prospective,randomized, controlled study comparing propofol and desflurane anesthesia

Laparoscopic surgery is often prolonged and requires positional changes to facilitate surgical access. Previous studies reported intraocular pressure (IOP) changes in one fixed position. This study investigated the effect of desflurane and propofol anesthesia on IOP during repeated positional changes. A total of 46 patients undergoing laparoscopic colorectal surgery were randomized into desflurane or propofol groups. IOP was measured using a handheld tonometer at seven time points: before induction (baseline), after endotracheal intubation, after pneumoperitoneum, after the first Trendelenburg and right tilt position, after reverse Trendelenburg and right tilt position, after the second Trendelenburg and right tilt position and before endotracheal extubation. Trendelenburg positioning raised IOP in both groups. In the desflurane group, IOP at the first Trendelenburg position was 6.27 and 8.48 mmHg higher than baseline IOP in left and right eye, respectively; IOP at the second Trendelenburg position was 7 and 9.44 mmHg higher than baseline in left and right eye, respectively. In the propofol group, IOP at the first Trendelenburg position was 2.04 and 4.04 mmHg higher than baseline in left and right eyes, respectively. It was 3.04 and 4.87 mmHg higher than baseline in left and right eye, respectively, at the second Trendelenburg position. In the desflurane group, 56.52% patients exhibited high IOP (≥?25 mmHg) compared with 13.04% in the propofol group at the second Trendelenburg position in the right eyes (P?=?0.005). There was a positive correlation between IOP and peak inspiratory pressure (P?<?0.001). Propofol anesthesia mitigated wide variations in IOP caused by repetitive positional changes during laparoscopic colorectal surgery.     

Predicting long-term outcomes after cardiac arrest by using serum neutrophil gelatinase-associated lipocalin

Objectives

Neutrophil gelatinase-associated lipocalin (NGAL) is secreted by various tissues in pathologic states. Previous studies reported that post-cardiac arrest serum NGAL levels correlate with short-term neurologic outcomes and survival. The aim of this study was to examine the associations between NGAL levels post-cardiac arrest and long-term outcomes and survival.

Diagnosis and Treatment of Patients with Thyroid Cancer

Background

Thyroid cancer is the most common malignancy of the endocrine system, representing 3.8% of all new cancer cases in the United States and is the ninth most common cancer overall. The American Cancer Society estimates that 62,450 people in the United States will be diagnosed with thyroid cancer in 2015, and 1950 deaths will result from the disease.

Objective

To review the current approach to the diagnosis and treatment of patients with thyroid cancer.

Discussion

Over the past 3 decades, there has been a dramatic increase in the number of people diagnosed with thyroid cancer, which may be attributable to the wide use of imaging studies, including ultrasounds, computed tomography, magnetic resonance imaging, and positron emission tomography scans that incidentally detect thyroid nodules. Thyroid cancer is divided into several main types, with papillary thyroid cancer being the most common. The treatment options for patients with thyroid cancer include the surgical removal of the entire thyroid gland (total thyroidectomy), radioactive iodine therapy, and molecular-targeted therapies with tyrosine kinase inhibitors. This article summarizes the diagnosis and treatment of thyroid cancer, with recommendations from the American Thyroid Association regarding thyroid nodules and differentiated thyroid cancer. Recently approved drugs and treatment trends are also explored.

Conclusion

The prognosis and treatment of thyroid cancer depend on the tumor type and its stage at the time of diagnosis. Many thyroid cancers remain stable, microscopic, and indolent. The increasing treatment options for patients with thyroid cancer, including therapies that were recently approved by the US Food and Drug Administration, have kept the mortality rate from this malignancy low, despite the increase in its incidence. Early diagnosis and appropriate treatment can improve prognosis and reduce mortality.     

Hypofractionated radiotherapy with Tomotherapy for patients with hepatic oligometastases: retrospective analysis of two institutions

To evaluate the efficacy and toxicity for patients with hepatic oligometastases, receiving hypofractionated radiotherapy with Tomotherapy to the liver. A total of 42 patients with 54 hepatic lesions, who had been treated from 2007 to 2011 at two institutions, were retrospectively reviewed for this study. All the patients received radical resections of the primary tumor, and had been presented with one to two hepatic lesions. The radiation dose of 40–75 Gy in 10–20 fractions (median, 50 Gy in 10 fractions) was delivered for the planning target volume. At a median follow-up time of 15 months, 1- and 2-year local control (LC) rates were 59.9 and 49.0 %, respectively. The 1- and 2-year overall survival (OS) rates were 60.0 and 44.0 %, respectively. Maximal tumor diameter of <3 cm and biologically effective dose (BED) of ≥100 Gy_α/β=10 were significantly associated with higher LC and OS. Primary colorectal cancer tended to be associated with higher LC (P = 0.075), and was significantly associated with higher OS (P = 0.037). 12 (28.6 %) of the 42 patients had grade 1–2 toxicities, and grade 3 or higher toxicity did not occur. Hypofractionated radiotherapy with Tomotherapy was safe for patients with hepatic oligometastases. The maximal tumor diameter of <3 cm and BED of ≥100 Gy_α/β=10 were significant prognostic factors for higher local control and survival, and primary colorectal cancer patients had statistically higher overall survival than the others.