CCK-8 enhances acid-sensing ion channel currents in rat primary sensory neurons.

Cholecystokinin (CCK) is a peptide that has been implicated in pain modulation. Acid sensitive ion channels (ASICs) also play an important role in pain associated with tissue acidification. However, it is still unclear whether there is an interaction between CCK signaling and ASICs during pain process. Herein, we report that a functional link between them in rat dorsal root ganglion (DRG) neurons. Pretreatment with CCK-8 concentration-dependently increased acid-evoked ASIC currents. CCK-8 increased the maximum response of ASICs to acid, but did not changed their acid sensitivity. Enhancement of ASIC currents by CCK-8 was mediated by the stimulation of CCK2 receptor (CCK2R), rather than CCK1R. The enhancement of ASIC currents by CCK-8 was prevented by application of either G-protein inhibitor GDP-ß-S or protein kinase C (PKC) inhibitor GF109203×, but not by protein kinase A (PKA) inhibitor H-89 or JNK inhibitor SP600125. Moreover, CCK-8 increased the number of action potentials triggered by acid stimuli by activating CCK2R. Finally, CCK-8 dose-dependently exacerbated acid-induced nociceptive behavior in rats through local CCK2R. Together, these results indicated that CCK-8/CCK2R activation enhanced ASIC-mediated electrophysiological activity in DRG neurons and nociception in rats. The enhancement effect depended on G-proteins and intracellular PKC signaling rather than PKA and JNK signaling pathway. These findings provided that CCK-8/CCK2R is an important therapeutic target for ASIC-mediated pain.

Clinical laboratory investigation of a patient with an extremely high D-dimer level: A case report.

BACKGROUND: D-dimer, a soluble degradation product of cross-linked fibrin, is commonly used as an important marker for the diagnosis of disseminated intravascular coagulation and differential diagnosis of thrombosis. Herein, we present a geriatric case with an unusually elevated D-dimer level. CASE SUMMARY: An 82-year-old woman, admitted to the ward with a diagnosis of chronic heart failure, was noted to have a remarkably elevated D-dimer level, beyond the qualified range (> 100 mg/L), utilizing the Innovating D-dimer for Sysmex CS-5100 System™. However, no evidence, including clinical symptoms, radiographic evidence of thromboembolic disease, and parallel fibrinogen degradation product values, suggested that this patient was at high risk of thrombopenia. To confirm the discrepancy, a series of approaches including sample dilution, re-analysis via alternative methods, and sample treatment with blockage of specific heterophilic antibodies were performed. A remarkable disappearance of the elevated D-dimer values was observed in the samples after they were subjected to these approaches (4.49, 9.42, 9.06, and 12.58 mg/L, respectively). This confirmed the presence of heterophilic antibodies in this case. In addition, a reduction in cardiac output due to the presence of cardiac failure could also be responsible for the existence of a hypercoagulable state in this case. CONCLUSION: In conclusion, the presence of heterophilic antibodies should be considered when an elevated D-dimer value is not in conformity with the clinical evidence, and a viral infection should be considered when interference by a heterophilic antibody exists.

CTLA-4 gene polymorphisms associate with efficacy of postoperative radioiodine-131 for differentiated thyroid carcinoma.

AIM: To investigate the association of CTLA-4 polymorphisms with efficacy of postoperative radioiodine-131 (I-131) treatment for differentiated thyroid carcinoma (DTC). METHODS: A total of 324 DTC patients and 350 healthy individuals were enrolled in our study. Patients received I-131 remnant ablation following surgical resection. Based on the treatment efficacy, patients were divided into the effective (n = 183) and ineffective groups (n = 141). CTLA-4 polymorphisms (+49A>G, CT60A>G and -318C>T) were genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: AG + AA genotype distribution and A allele frequency of +49A>G and CT60A>G polymorphisms were higher in the effective group than the ineffective group. CONCLUSION: +49A>G and CT60A>G polymorphisms were associated with the efficacy of postoperative I-131 treatment for DTC; and they might be bioindicators related to the prognosis of I-131 treatment.

Relationship between VEGF protein expression and lymph node metastasis in papillary thyroid carcinoma among Asians: a meta-analysis.

We carried out the current meta-analysis of relevant cohort studies in an attempt to investigate the relationships between vascular endothelial growth factor (VEGF) protein expression and lymph node (LN) metastasis in papillary thyroid carcinoma (PTC) among Asians. A range of electronic databases were searched, including Web of Science (1945∼2013), the Cochrane Library Database (Issue 12, 2013), MEDLINE (1966∼2013), EMBASE (1980∼2013), CINAHL (1982∼2013), and Chinese Biomedical Database (CBM) (1982~2013) with cross-referencing without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. Crude odds ratio (OR) with their 95 % confidence interval (95 %CI) was calculated. Twelve clinical cohort studies with a total of 1,045 PTC patients were included in our meta-analysis, The results of our meta-analysis revealed that patients with VEGF-positive tumors had a 3.02-fold higher risk of LN metastasis than that of patients with VEGF-negative tumors (OR=3.02, 95 %CI=2.05~4.43, P<0.001). Furthermore, subgroup analysis by country suggested that VEGF-positive expression was associated with an increased risk of LN metastasis in PTC patients among Chinese populations (OR=3.33, 95 %CI=2.30~4.83, P<0.001), but not among Korean, Turkish, and Japanese populations (all P>0.05). Our findings support the view that VEGF protein expression may be correlated with LN metastasis in PTC patients, especially among Chinese populations.