C5a anaphylatoxin is a major regulator of activating versus inhibitory FcgammaRs in immune complex-induced lung disease

IgG Fc receptors (FcgammaRs, especially FcgammaRIII) and complement (in particular, C5a anaphylatoxin) are critical effectors of the acute inflammatory response to immune complexes (ICs). However, it is unknown whether and how these two key components can interact with each other in vivo. We use here a mouse model of the acute pulmonary IC hypersensitivity reaction to analyze their potential interaction. FcgammaRIII and C5aR are coexpressed on alveolar macrophages (AMs), and both FcgammaRIII and C5aR mutant mice display impaired immune responses. We find that recombinant human C5a (rhC5a) can control inverse expression of various FcgammaRs, and costimulation of ICs with rhC5a results in strong enhancement of FcgammaRIII-triggered cellular activation in vitro and in vivo. Moreover, we show here that early IC-induced bioactive C5a, and its interaction with C5aR, causes induction of activating FcgammaRIII and suppression of inhibitory FcgammaRII on AMs that appears crucial for efficient cytokine production and neutrophil recruitment in lung pathology. Therefore, C5a, which is a potent chemoattractant, has a broader critical function in regulating the inhibitory/activating FcgammaRII/III receptor pair to connect complement and FcgammaR effector pathways in immune inflammation.     

Hemoglobin Hasharon (α247 his(CD5)β2): a hemoglobin found in low concentration

Hemoglobin Hasharon (alpha(2) (47 his)(CD5)beta(2)) was found to comprise only 16-19% of hemolysates of carriers. These heterozygotes appeared to have mild, compensated, hemolytic anemia. Hb Hasharon was more heat-labile than hemoglobins A, S, or C. Its specific activity was higher than that of Hb A after administration of (59)Fe to two carriers. When hemoglobin synthesis by bone marrow cells was studied in vitro, about 18% of incorporated leucine appeared in the Hb Hasharon fraction. It is suggested that Hb Hasharon is unstable in vivo, and that mild hemolytic anemia and a relatively small decrease in its concentration in hemolysates result from its denaturation within red cells. Decreased synthesis, which appears to be the major cause of the small amount of abnormal hemoglobin, may protect heterozygotes from clinically significant hemolytic anemia.     

The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule

Background  

Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and Haemophilus influenzae type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib_2.5 [Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib_2.5 [Kft] was not inferior to the licensed DTPw-HBV/Hib (Tritanrix(tm)-HepB/Hiberix(tm)) vaccine or the DTPw-HBV/Hib_2.5 vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age.     

A modified lightwand-guided nasotracheal intubation technique for oromaxillofacial surgical patients

Study ObjectiveTo investigate the efficiency of a double curve nasotracheal tube on lightwand-guided nasotracheal intubation.DesignProspective, randomized, controlled trial.SettingUniversity medical center hospital.Patients60 ASA physical status I and II patients undergoing oromaxillofacial surgery.Interventions and MeasurementsPatients undergoing surgery with nasotracheal intubation and general anesthesia were randomly enrolled in the laryngoscopy group or the lightwand group. The same type of double curve nasotracheal tube was used in both groups. In the laryngoscopy group, intubation was assisted with a Macintosh No. 3 standard curved blade and Magill forceps. In the lightwand group, intubation was aided with a flexible lightwand device (without the inner stiff stylet). Intubation time was divided into two parts: Part one, from selected naris to oropharynx; Part two, from oropharynx into trachea. Part one, Part two, and total intubation time, hemodynamic responses to nasotracheal intubation, and adverse events or complications were recorded.Main ResultsTotal intubation times in the lightwand group and the laryngoscopy group were 22.8 ± 8.0 sec vs 30.3 ± 8.2 sec (P < 0.001), respectively. The lightwand group had comparable hemodynamic responses to those of the laryngoscopy group. Adverse events and complications were all self-limited, with similar occurrence in both groups.ConclusionFor patients undergoing oromaxillofacial surgery, modified lightwand-guided nasotracheal intubation is feasible with a double curve nasotracheal tube and is an efficient alternative technique.     

A rare case of cardiogenic shock caused by takotsubo syndrome associated with SARS-CoV-2 infection: The value of echocardiography in the diagnosis and monitoring of the efficacy of extracorporeal membrane oxygenation

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mainly invades the respiratory system, but may also cause various cardiovascular complications. We report a rare case of myocarditis associated with SARS-CoV-2 infection. A 61-year-old man was admitted to the hospital with a positive nucleic acid test for SARS-CoV-2. A sudden increase in troponin level (up to .144 ng/mL) was observed on the 8th day after admission. He developed symptoms of heart failure and progressed rapidly to cardiogenic shock. Echocardiography on the same day showed reduced left ventricular ejection fraction, reduced cardiac output, and segmental ventricular wall motion abnormalities. Takotsubo cardiomyopathy associated with SARS-CoV-2 infection was considered based on the typical echocardiography findings. We immediately started veno-arterial extracorporeal membrane oxygenation (VA-ECMO) treatment. The patient was successfully withdrawn from VA-ECMO after 8 days following recovery of ejection fraction to 65% and all indicators qualifying the withdrawal criteria. Echocardiography plays an important role in dynamic monitoring of cardiac changes in such cases and can help determine the timing of extracorporeal membrane oxygenation treatment and withdrawal.     

Synthesis and mixed lineage kinase activity of pyrrolocarbazole and isoindolone analogs of (+)K-252a

Structural modification of the indolecarbazole natural product (+)K-252a identified structural requirements for MLK activity and a novel series of potent fused pyrrolocarbazole MLK1/3 inhibitors. The SAR revealed that the lactam regiochemistry, the shape of the heterocycle, and aryl rings B and F are important to MLK activity. Heteroatom and alkyl replacement of the N-12 and/or N-13 indole nitrogen atoms identified the nonplanar dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-7-one (8) and corresponding 5,7-dione (7) as potent cell-permeable MLK1/3 family-selective leads with in vitro activity comparable to that of (+)K-252a and determined them to be 2- to 3-fold more potent than the aglycone natural product K-252c.