Recombinant Protein Mimicking the Antigenic Structure of the Viral Surface Envelope Protein Reinforces Induction of an Antigen-Specific and Virus-Neutralizing Immune Response Against Dengue Virus.

Dengue virus (DENV), belonging to the family Flaviviridae, is the causative agent of dengue and comprises four serotypes. A second heterologous DENV infection is a critical risk factor for severe dengue, and no effective vaccine is available to prevent infection by all four DENV serotypes. Recombinant DENV vaccines are primarily based on the envelope proteins, prM and E. The E protein and its envelope domain III (EDIII) have been investigated as candidate antigens (Ags) for recombinant subunit vaccines. However, most EDIII-based Ags are monomers that do not display the cognate antigenic structure of E protein, which is essential for induction of virus-neutralizing immunity. Here, we developed recombinant DENV-2 envelope domain (r2ED) protein as an Ag that mimics the quaternary structure of E protein on the DENV surface. We confirmed that r2ED retained the conformational epitope displayed at the E-dimer interface, which reportedly exhibits broad virus-neutralizing capacity, without displaying the fusion loop epitope that causes antibody (Ab)-dependent enhancement. Furthermore, compared with EDIII alone, r2ED elicited stronger Ag-specific and cross-reactive neutralizing Ab and T cell-mediated immune responses in mice. This Ag-specific immunity was maintained at an elevated level 6 months after the last immunization, suggesting sustained Ag-specific immune memory. Taken together, these observations suggest that r2ED could be used to develop an improved subunit vaccine capable of inducing a broadly cross-reactive and long-lasting immune response against DENV infection.

Efficacy of sphenopalatine ganglion block in nasal mucosal headache presenting as facial pain.

Background: When intranasal contact points are the cause of headache and facial pain, opinions regarding whether to remove intranasal contact points when they are believed to be the cause of headache and facial pain are divided.Clinical Presentation: A 46-year-old woman visited the authors' pain clinic with complaints of right nasal pain accompanied by frontotemporal headache. She first met an Otorhinolaryngologist and a neurologist. Based on nasal endoscopy and pain pattern, they presumed that her pain was a nasal mucosal headache rather than migraine. A mild septal deviation to the right side with bony spur near the inferior turbinate was observed. The use of medication provided very insufficient relief. However, the sphenopalatine ganglion (SPG) block provided excellent pain relief, and the effect lasted for six months.Conclusion: Considering the mechanism of pain in intranasal contact point headache, (SPG) block is a potentially effective therapeutic tool.

Does Equi-Minimum Alveolar Concentration Value Ensure Equivalent Analgesic or Hypnotic Potency?: A Comparison between Desflurane and Sevoflurane.

BACKGROUND: Minimum alveolar concentration (MAC) has traditionally been used to compare the potency of volatile anesthetics. However, as it reflects the spinal mechanism of immobility rather than the cerebral mechanism of analgesia and hypnosis, it is doubtful that equi-MAC connotes equivalent analgesic or hypnotic potency. The level of analgesia and hypnosis can be assessed using surgical pleth index and bispectral index (BIS) values, respectively. This study was designed to compare the surgical pleth index and BIS values produced by equi-MAC of desflurane and sevoflurane in patients undergoing single-agent volatile anesthesia. METHODS: Eighty-nine patients were randomly allocated to two groups receiving either desflurane (n = 44) or sevoflurane (n = 45). Anesthesia was only maintained with assigned volatile anesthetic of age-corrected 1.0 MAC. Surgical pleth index values as an analgesic estimate and BIS values as a hypnotic estimate were obtained under standard tetanic stimulation. RESULTS: Post-stimulation surgical pleth index values (mean ± SD), the primary outcome, were significantly lower for the desflurane group than those for the sevoflurane group (49 ± 10 vs. 64 ± 14, difference, 15 [95% CI, 10 to 20], P < 0.001). The desflurane group showed significantly lower poststimulation BIS values (median [interquartile range]) than the sevoflurane group (36 [31 to 41] vs. 41 [38 to 47], difference, 6 [95% CI, 2 to 9], P = 0.001). CONCLUSIONS: During a steady-state of 1.0 MAC, desflurane and sevoflurane did not cause similar surgical pleth index and BIS values under the standardized nociceptive stimulus. These findings suggest that equi-MAC of desflurane and sevoflurane may not ensure equivalent analgesic or hypnotic potency. VISUAL ABSTRACT: An online visual overview is available for this article at http://links.lww.com/ALN/B726.

[Effect of low dose 5-fluorouracil and cisplatin intra-arterial infusion chemotherapy in advanced hepatocellular carcinoma with decompensated cirrhosis].

BACKGROUND/AIMS: Advanced hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) has a poor prognosis. The aim of this study was to evaluate the efficacy and safety of repeated arterial infusions of low dose cisplatin and 5-fluorouracil (FU) in patients with advanced HCC with decompensated cirrhosis. METHODS: Between January 1995 and December 2003, a total of 79 decompensated cirrhotic patients having HCC and PVT were enrolled and divided into 2 groups. Group 1 (n=40) received intra-arterial infusion chemotherapy with cisplatin (10 mg for 5 days) and 5-FU (250 mg for 5 days) via an implanted chemoport every 4 weeks' and group 2 (n=39) was managed with only conservative treatment. RESULTS: The two groups were well matched with respect to the features relating to the prognosis, including age, gender and the Child- Pugh class. Although diffuse tumor involvement, main portal vein tumor thrombosis and bi-lobar involvement were more frequent in group 1, the median survival period of group 1 was significantly longer than group 2 (5 months vs. 3 months, respectively, P=0.016). Also, the 1-year survival rate of group 1 (7.5%) was higher than that of group 2 (5.1%) (P=0.016). When we analyzed the patients with the Child class B, the survival benefits of intra-arterial chemotherapy were more significant (P=0.008). CONCLUSIONS: Intra-arterial chemotherapy consisting of low dose 5-FU and cisplatin achieved favorable results for advanced HCC patients who had decompensated cirrhosis, and it showed better survival in selected patients. This therapy may be useful as a palliative treatment for HCC patients with decompensated cirrhosis.

[Efficacy of AST to platelet ratio index in predicting severe hepatic fibrosis and cirrhosis in chronic hepatitis B virus infection].

BACKGROUND/AIMS: An ideal noninvasive diagnostic test for hepatic fibrosis should be simple, inexpensive, and accurate. We aimed to find the simple marker for predicting hepatic fibrosis and to compare the accuracy of AST, platelet, AST/ALT ratio and AST to platelet ratio index (APRI) in chronic hepatitis B patients without clinical evidence of cirrhosis. METHODS: A total of one hundred and twenty-six chronic hepatitis B patients who underwent liver biopsy at the Ajou University Hospital from August 1998 to December 2003 were enrolled. Hepatic fibrosis was assessed using the Ludwig classification. Significant fibrosis was defined as fibrosis score of 3 or more. The AST/ALT ratio and APRI were calculated and correlations with hepatic fibrosis were analyzed. RESULTS: APRI showed a significant correlation (r=0.501, p=0.000) with hepatic fibrosis, and was superior to AST, AST/ALT ratio and platelet in predicting fibrosis. Patients with significant fibrosis (fibrosis stage 3, 4) can be identified to have APRI = 1 with sensitivity 71.2% and specificity 70.3%. The sensitivity and specificity of an APRI = 1.5 for cirrhosis (stage 4) were 83.3% and 75.0%. CONCLUSIONS: Simple index using AST and platelet value can predict the presence of significant fibrosis and cirrhosis in chronic hepatitis B patients without clinical evidence of cirrhosis.