Hot receptors in the brain

Two major approaches have been employed for the development of novel drugs to treat chronic pain. The most traditional approach identifies molecules involved in pain as potential therapeutic targets and has focused mainly on the periphery and spinal cord. A more recent approach identifies molecules that are involved in long-term plasticity. Drugs developed through the latter approach are predicted to treat chronic, but not physiological or acute, pain. The TRPV1 (transient receptor potential vanilloid-1) receptor is involved in nociceptive processing, and is a candidate therapeutic target for pain. While most research on TRPV1 receptors has been conducted at the level of the spinal cord and peripheral structures, considerably less research has focused on supraspinal structures. This short paper summarizes progress made on TRPV1 receptors, and reviews research on the expression and function of TRPV1 receptors in supraspinal structures. We suggest that the TRPV1 receptor may be involved in pain processing in higher brain structures, such as the anterior cingulate cortex. In addition, some regions of the brain utilize the TRPV1 receptor for functions apparently unrelated to pain

Cingulate NMDA NR2B receptors contribute to morphine-induced analgesic tolerance

Morphine is widely used to treat chronic pain, however its utility is hindered by the development of tolerance to its analgesic effects. While N-methyl-D-aspartate (NMDA) receptors are known to play roles in morphine tolerance and dependence, less is known about the roles of individual NMDA receptor subtypes. In this study, Ro 256981, an antagonist of the NMDA receptor subunit NR2B, was used to reduce the expression of analgesic tolerance to morphine. The mechanisms altered with chronic drug use share similarities with those underlying the establishment of long-tem potentiation (LTP) and behavioral memory. Since NMDA NR2B receptors in the anterior cingulate cortex (ACC) play roles in the establishment of LTP and fear memory, we explored their role in changes that occur in this region after chronic morphine. Both systemic and intra-ACC inhibition of NR2B in morphine-tolerant animals inhibited the expression of analgesic tolerance. Electrophysiological recordings revealed a significant increase in the NR2B component of NMDA receptor mediated excitatory postsynaptic currents (EPSCs), at both synaptic and extra-synaptic sites. However, there was no change in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor mediated EPSCs. This study suggests that selective inhibition of NMDA NR2B receptors may prove useful in combating the development of analgesic tolerance to morphine and proposes a novel role for the ACC in opioid tolerance and morphine induced changes in synaptic plasticity

Elastography Can Effectively Decrease the Number of Fine-Needle Aspiration Biopsies in Patients with Calcified Thyroid Nodules

AbstractWhen calcification, frequently found in both benign and malignant nodules, is present in thyroid nodules, non-invasive differentiation with ultrasound becomes challenging. The goal of this study was to evaluate the utility of elastography in differentiating calcified thyroid nodules. Consecutive patients (165 patients with 196 nodules) referred for fine-needle aspiration who had undergone both ultrasound elastography and B-mode examinations were analyzed retrospectively. Calcification was present in 45 benign and 20 malignant nodules. On 65 calcified nodules, elastography had 95% sensitivity, 51.1% specificity, 46.3% positive predictive value and 95.8% negative predictive value in detecting malignancy. Twenty-three of 45 benign calcified nodules were correctly diagnosed with elastography compared with 4 of 45 by B-mode ultrasound. Although it is difficult to differentiate benign and malignant calcified thyroid nodules solely with B-mode ultrasound, elastography has the potential to reduce the number of fine-needle aspiration biopsies performed on calcified nodules

Antioxidant and Hepatoprotective Effects of Procyanidins fromWild Grape (Vitis amurensis) Seeds in Ethanol-Induced Cells and Rats

In the present study, we characterized the antioxidant and hepatoprotective mechanisms underlying of wild grape seed procyanidins (WGP) against oxidative stress damage in ethanol-treated HepG2 cell and Sprague-Dawley (SD)-rat models. In HepG2 cells, WGP not only diminished the ethanol (EtOH, 100 mM)-induced reactive oxygen species (ROS) formation and cytochrome P450 2E1 (CYP2E1) expression, but also renovated both the activity and expression of antioxidant enzymes including catalase, superoxide dismutase, and glutathione peroxidase. Additionally, to investigate the hepatoprotective effect of WGP, rats were orally administered 10 or 50 mg/kg WGP once daily for seven days prior to the single oral administration of EtOH (6 g/kg). The results show that WGP administration decreased the EtOH-induced augment of the levels of serum aspartate transaminase and alanine transaminase as well as serum alcohol and acetaldehyde. WGP treatment upregulated the activities and protein levels of hepatic alcohol dehydrogenase, aldehyde dehydrogenase, and antioxidant enzymes but downregulated the protein expression level of liver CYP2E1 in EtOH-treated rats. Moreover, the decreased phosphorylation levels of mitogen activated protein kinases (MAPKs) by ethanol were induced in both HepG2 cell and rat models. Overall, pretreatment of WGP displayed the protective activity against EtOH-mediated toxicity through the regulation of antioxidant enzymes and alcohol metabolism systems via MAPKs pathways

Symptomatic epidural gas cyst treated with epidural block and percutaneous needle aspiration -A case report-

A 68-year-old woman suffered from lower back and radiating pain on her right buttock and posterior calf. Axial magnetic resonance imaging showed a 7 × 7 mm nodular lesion (T1 and, T2 low signal intensity) at the epidural space between the L5-S1 level and computed tomography revealed it was an epidural gas cyst. The authors performed an epidural block and percutaneous needle aspiration of the epidural gas cyst. The patient showed almost complete resolution of symptoms one year later. The authors suggest that an epidural nerve block with needle aspiration of a gas cyst could be an alternative treatment option for patients with a symptomatic epidural gas cyst before surgery

The Effects of Glyburide on Apoptosis and Endoplasmic Reticulum Stress in INS-1 Cells in a Glucolipotoxic Condition

Backgroundβ-cell death due to endoplasmic reticulum (ER) stress has been regarded as an important pathogenic component of type 2 diabetes. The possibility has been suggested that sulfonylurea, currently being used as one of the main oral hypoglycemic agents of type 2 diabetes, increases ER stress, which could lead to sulfonylurea failure. The authors of the present study examined ER stress of β-cells in a glucolipotoxic condition using glyburide (GB) in an environment mimicking type 2 diabetes.MethodsApoptosis was induced by adding various concentrations of GB (0.001 to 200 µM) to a glucolipotoxic condition using 33 mM glucose, and the effects of varied concentrations of palmitate were evaluated via annexin V staining. The markers of ER stress and pro-apoptotic markers were assessed by Western blotting and semi-quantitative reverse transcription-polymerase chain reaction. Additionally, the anti-apoptotic markers were evaluated.ResultsAddition of any concentration of GB in 150 µM palmitate and 33 mM glucose did not increase apoptosis. The expression of phosphorylated eukaryotic initiation factor (eIF-2α) was increased and cleaved caspase 3 was decreased by adding GB to a glucolipotoxic condition. However, other ER stress-associated markers such as Bip-1, X-box binding protein-1, ATF-4 and C/EBP-homologous protein transcription factor and anti-apoptotic markers phosphor-p85 phosphatidylinositol 3-kinase and phosphorylation of Akt did not change significantly.ConclusionGB did not show further deleterious effects on the degree of apoptosis or ER stress of INS-1 cells in a glucolipotoxic condition. Increased phosphorylation of eIF-2α may attenuate ER stress for adaptation to increased ER protein load

Delta neutrophil index as a predictor of vesicoureteral reflux in children with febrile urinary tract infection

Purpose Delta neutrophil index (DNI) indicates immature granulocytes in peripheral blood and has been confirmed to be effective as a prognostic factor for neonatal sepsis. Also, it has been reported to have diagnostic value in acute pyelonephritis and in predicting vesicoureteral reflux (VUR) in the infant. We conducted the study to verify whether DNI is also helpful in the entire pediatric age group with febrile urinary tract infection (UTI). Methods Medical records of children hospitalized for febrile UTIs were analyzed retrospectively. All subjects underwent kidney ultrasound and voiding cystourethrography. In the group with and without VUR, we compared sex and age, and the following laboratory values: the white blood cell count, neutrophil, polymorphonuclear leucocyte, eosinophil, hemoglobin, platelet count, C-reactive protein, DNI value, and the finding of ultrasound. Results A total of 315 patients (163 males and 152 females; range, 0–127 months) were eligible, and 41 patients (13%) had VUR. As a result of univariate analysis, the white blood cell count, neutrophil, DNI, and ultrasonic abnormalities were high in the reflux group, and the hemoglobin and lymphocyte fraction values were low. The value of DNI and the abnormal ultrasound were significantly higher in the reflux group on the multivariate analysis. The area under the curve value of the receiver operating curve was higher in DNI (0.640; 95% confidence interval, 0.536–0.744; P=0.004), and the DNI cutoff value for VUR prediction was 1.85%. Conclusions We identified that ultrasound findings and DNI values were helpful predictors of VUR in pediatric febrile UTIs