Macitentan in Pulmonary Arterial Hypertension: A Focus on Combination Therapy in the SERAPHIN Trial

American Journal of Cardiovascular Drugs - SERAPHIN was a double-blind, placebo-controlled, event-driven phase III trial that evaluated the effects of long-term treatment with macitentan, an oral...     

Reproducibility of sonographic measurement of the substantia nigra

The aim of this study was to evaluate inter-reader, intra-investigator and inter-investigator reproducibility and correlations in the assessment of substantia nigra (SN) echogenicity and area measurement by a physician-sonographer (PS), a sonographic laboratory assistant (SLA) and a physician without sonographic experience (PN). A total of 22 patients with extrapyramidal symptoms were examined using transcranial sonography (TCS). SN images were encoded and evaluated by the three readers. A second TCS examination was performed after 7+/-2 d. A second investigator performed TCS examination 1 mo later. Spearman rank correlation and Pearson's correlation coefficient were used when assessing the agreement between readers. All three readers identified the same 15 patients with SN echogenicity III or more. Inter-reader SN echogenicity and area measurement correlations were r=0.55 to 0.82 and r=0.31 to 0.74 between PS and SLA and r=0.55 to 0.77 and 0.49 to 0.62 between PS and PN, respectively (p<0.05 in all cases). Intra-reader echogenicity and area measurement correlations (r=0.85 to 0.96 and r=0.51 to 0.69) were statistically significant only for PS (p<0.001). All intra- and inter-investigator correlations of SN area measurement (r=0.69 to 0.88 and r=0.5 to 0.61) and SN echogenicity (r=0.64 to 0.92 and r=0.51 to 0.69) were statistically significant (p<0.05). Semiquantitative evaluation of SN echogenicity and area using TCS is highly dependent on the experience of the sonographer. Only an experienced sonographer was able to produce very reproducible results with statistically significant correlations; SLA and PN intra-reader correlations were poor.     

Does status epilepticus modify the effect of ifenprodil on cortical epileptic afterdischarges in immature rats?

Background

Ifenprodil as a specific antagonist of NMDA receptors containing a dominant NR2B subunit exhibits age-dependent anticonvulsant action. Possible changes of this action due to status epilepticus (SE) elicited at early stage of development were studied using cortical epileptic afterdischarges (ADs) as a model.

Muscle transfers in children and adults improve external rotation in cases of obstetrical brachial plexus paralysis: a comparative study

Purpose

Latissimus dorsi and teres major transfers to the lateral side of the humerus with lengthening of the pectoralis major and subscapularis muscles for residual shoulder deformity were compared in children and skeletally mature patients.

Methods

Fifteen patients (nine children, six skeletally mature patients aged three to 30 years, follow-up one to 22 years) were treated for internal shoulder contracture after birth plexus lesions: C5–C6 (seven patients); C5–7 (five patients); C5-C8-T1 (three patients, respectively). Range of movement, Mallet shoulder function score and radiographs were assessed.

Results

Pre-operatively, shoulder function restrictions were comparable in all patients. Postoperatively, external rotation, abduction and Mallet function score improved significantly (p < 0.05) in all patients except one. There were no differences in improvement between children and skeletally mature patients (p = 0.24–1.0).

Conclusions

This technique improves external rotation and abduction of the shoulder for daily living activities in children and young, skeletally mature, patients.     

Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus,Respiratory Syncytial Virus and Influenza A Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca²⁺ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.     

Mechanistic study of 1,1-dimethylhydrazine transformation over Pt/SiO2 catalyst

Catalytic oxidation of 1,1-dimethylhydrazine (UDMH) with molecular oxygen over Pt/SiO₂ was studied by in situ FTIR spectroscopy coupled with online MS monitoring of the gas phase. An unusual two-step oxidation process was detected in experiments with the pulse UDMH feeding: initial UDMH oxidation over a fresh platinum surface quickly terminates due to the blockage of active sites; a time-separated second oxidation step corresponds to combustion of the surface residue. This residue consists of C N nitrile groups formed via decomposition of the products of non-oxidative UDMH conversion, such as dimethylamine. The two-step oxidation picture is observed over a broad range of reaction temperatures and oxygen to UDMH ratios.

Unusual two-step oxidation process of 1,1-dimethylhydrazine on Pt/SiO₂ catalyst.