Comparing recombinant human rabies monoclonal antibody (ormutivimab) with human rabies immunoglobulin (HRIG) for postexposure prophylaxis: A phase III, randomized, double-blind, non-inferiority trial.

OBJECTIVES: To evaluate the immunogenicity and safety of an anti-rabies monoclonal antibody (mAb), ormutivimab, compared with human rabies immunoglobulin (HRIG). METHODS: This phase III trial was designed as a randomized, double-blind, non-inferiority clinical trial in patients aged ≥18 years with suspected World Health Organization category Ⅲ rabies exposure. The participants were randomized 1:1 to ormutivimab and HRIG groups. After thorough wound washing and injection of ormutivimab/HRIG on day 0, the vaccination was administered on days 0, 3, 7, 14, and 28. The primary endpoint was the adjusted geometric mean concentration (GMC) of rabies virus-neutralizing activity (RVNA) on day 7. The endpoint of safety included the occurrence of adverse reactions and serious adverse events. RESULTS: A total of 720 participants were recruited. The adjusted-GMC of RVNA (0.41 IU/ml) on day 7 in ormutivimab group was not inferior to that in the HRIG group (0.41 IU/ml), with ratio of adjusted-GMC of 1.01 (95% confidence interval: 0.91, 1.14). The seroconversion rate of the ormutivimab group was higher than that of the HRIG group on days 7, 14, and 42. Most local injection sites and systemic adverse reactions reported from both groups were mild to moderate in severity. CONCLUSION: ormutivimab + vaccine can protect victims aged ≥18 years with category Ⅲ suspected rabies exposure as a component of postexposure prophylaxis. ormutivimab has a weaker influence on the immunity response of rabies vaccines. CLINICAL TRIALS REGISTRATION: ChiCTR1900021478 (the Chinese Clinical Trial Registry of World Health Organization).

Amamiclytus wuxingensis sp. nov. (Coleoptera, Cerambycidae), the third species of the genus from mainland China.

Amamiclytus wuxingensis sp. nov., the third species of the genus from mainland China, is described and illustrated with specimens collected from Wuxing Village, Leishan County, Guizhou Province, China. Distribution and grouping of the new species are discussed and the key to the East Asian species of the genus is updated to accommodate species recorded from mainland China.

[The preparation, identification and physicochemical properties of anti-Porphyromonas gingivalis IgY].

OBJECTIVE: To obtain egg yolk antibody in hen eggs laid by hens immunized with the protein of Porphyromonas gingivalis (Pg). To generate, purify IgY against Pg (anti-Pg-IgY) and identify its specificity. METHODS: PgATCC33277 was cultured under standard anaerobic conditions and harvested after proliferation. Then Pg was extracted by sonication until the cell pellets were shattered completely. After centrifugatiton, the supernatant was collected. Five-month-old Roman hens were immunized for egg antibody production. The antibody was inoculated intramuscularly and subcutaneously in the breast from multiple spot with 1.0 ml of a vaccine consisting of oil-adjuvant protein which was mixed with 1 ml protein of Pg and 1 ml Freund's adjuvant complete every 10 days, for 4 times. The eggs were collected after the first immunization and stored at 4°C. The anti-Pg-IgY was extracted and purified. The protein concentration was tested by bicinchoninic acid (BCA), the specificity of IgY analyzed by SDS polyacrylamide gel electrophoresis (SDS-PAGE), the titre of IgY and its physicochemical character were evaluated by indirect enzyme-linked immunosorbent assay. RESULTS: The concentration of obtained anti-Pg-IgY was 2.05 g/L. SDS-PAGE analysis of the anti-Pg-IgY showed that the molecular weight of IgY was consistent with the theoretical value. Protein of anti-Pg-IgY appeared approximately 5 days after the first immunization, and reached the peak at 50 - 55 days. Antibody titres reached 1:100 000. Each egg produced more than 10 mg IgY, and its purification was up to 95% as well. CONCLUSIONS: Layer hens immuned by Pg may provide specific IgY of high titre and high concentration. The antibody has high purity and is heat, acid and alkali-resistant.

Proteasome inhibition potentiates the cytotoxic effects of hyperthermia in HT-29 colon cancer cells through inhibition of heat shock protein 27.

BACKGROUND: The purpose of this study was to investigate whether proteasome inhibition acts as a thermal sensitizing agent to induce tumor cell death in a colon cancer cell line. METHODS: HT-29 colon cancer cells were exposed to hyperthermia (43 degrees C) in the presence of proteasome inhibition for 1 h. Viable cell mass and apoptosis were measured by MTT and annexin V staining, respectively. Protein levels were determined by Western blot analysis. RESULTS: A significant synergistic effect on cell viability with proteasome inhibition was noted under hyperthermic conditions compared to hyperthermia alone (p < 0.05). Increases in phosphorylated ERK and decreases in HSP27 levels were observed in the cells exposed to proteasome inhibition at 43 degrees C. Pretreatment with an inhibitor of ERK yielded an additional increase in apoptosis when used in combination with proteasome inhibition and hyperthermia. Decreased expression of HSP27 by siRNA also resulted in increased thermally induced apoptotic cell death. CONCLUSIONS: Thermal sensitization through proteasome inhibition may represent a novel approach to increase the efficacy of hyperthermia as an anticancer modality.

Early administration of intracoronary verapamil improves myocardial perfusion during percutaneous coronary interventions for acute myocardial infarction.

BACKGROUND: Intracoronary calcium-channel blockers administered in the event of no reflow during percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) have been shown to improve myocardial perfusion. STUDY OBJECTIVE: To evaluate the effects of the administration of intracoronary verapamil before the occurrence of no reflow during direct PCI. DESIGN AND SETTING: Single-center, nonrandomized, prospective study with a retrospective control group. PATIENTS AND METHODS: From September 2001 to December 2003, 50 consecutive patients with AMI were prospectively enrolled for intracoronary verapamil treatment. Intracoronary verapamil was administered immediately prior to balloon inflation and at short intervals during the procedure thereafter. Retrospectively, 50 consecutive AMI patients who had undergone direct PCI and had not received intracoronary calcium-channel blockers were enrolled as control subjects. Patients with cardiogenic shock or platelet glycoprotein IIb/IIIa inhibitor were excluded. Thrombolysis in Myocardial Infarction (TIMI) flow grade, corrected TIMI frame count (CTFC), and TIMI myocardial perfusion grade (TMPG) were assessed prior to and following PCI by two independent cardiologists blinded to the procedures. RESULTS: The two groups had similar baseline and post-procedural angiographic characteristics, although the patients who been administered verapamil received more stent implantations than the control subjects (84% vs 60%, p = 0.008). Post-procedural TIMI flow < 3 (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.12 to 1.30; p = 0.18) and TMPG (OR, 1.24; 95% CI, 0.46 to 3.34; p = 0.68) were not associated with the implantation of the stents. There were no significant difference in post-PCI TIMI flow (p = 0.68) and CTFC (p = 0.36) between patients treated with verapamil and the control subjects. Post-PCI TMPG was significantly better in patients treated with intracoronary verapamil (p = 0.003). Forty-two percent of the patients treated with verapamil were found to have TMPG-3, while only 14% of the control subjects were found to have the same degree of TMPG (p = 0.004). Treatment with intracoronary verapamil (OR, 0.26; 95% CI, 0.12 to 0.58; p = 0.001) and pre-PCI TIMI flow (OR, 0.54; 95% CI, 0.35 to 0.84; p = 0.006) were found by multiple logistic regression to be independent predictors of TMPG. CONCLUSIONS: Early administration of intracoronary verapamil during direct PCI improves post-procedural myocardial perfusion, as evaluated by TMPG.