Effect of valproic acid on the pharmacokinetic profile of oxcarbazepine in the rat

The pharmacokinetics of oxcarbazepine (30 mg kg-1, po), administered for 1 week, was studied in rats pre-treated for 2 weeks with valproic acid (100 mg kg-1, po). Oxcarbazepine (OXC) plasma levels were measured over a period of 24 h from dosing, using a sensitive HPLC method. No significant changes were observed in the mean values of OXC pharmacokinetic parameters (Cmax, Tmax, t1/2 and AUC0-infinity) between the control and the pre-treated groups. The findings of this study suggest that OXC metabolism in the rat is apparently not affected by valproic acid, and the lack of effect may be attributed to the different pathways of biotransformation of the two drugs.     

Initiation of the extrinsic pathway of coagulation by human and rabbit alveolar macrophages: a kinetic study

We examined assembly and expression of the factor X activating complex on human and rabbit alveolar macrophages. Kinetic parameters of the factor X activating reaction were determined by functional titrations of factors VII and X with macrophage tissue factor (TF) added. We found rapid activation of factor X to Xa on alveolar macrophage surfaces. Detection of rapid factor Xa formation on macrophages required addition of exogenous factors VII and X. At plasma concentrations of the purified factors, factor Xa was formed on freshly isolated macrophages at approximately 5.4 pmol/min/10(6) cells. After macrophage maturation in culture for 20 hours with LPS (endotoxin) added, the factor X activation rate was increased two- to sixfold. The km' (apparent km) of TF-factor VII enzymatic complexes assembled on alveolar macrophages for factor X were (258 +/- 55 and 475 +/- 264 nmol/L for human and rabbit cells, respectively). The km' did not change during macrophage maturation in culture, but V'max (apparent Vmax) was consistently increased. The K1/2 of human factor VII (concentrations giving half maximal rates of factor X activation) for the interaction with human and rabbit alveolar macrophage TF were 0.191 +/- 0.096 and 1.7 +/- 0.7 etamol/L, respectively. The K1/2 were not significantly changed after maturation, whereas rates of Xa formation at saturation with factor VII were increased. The fast rates of factor X activation observed at physiologic concentrations of plasma-derived factors VII and X indicate that TF on alveolar macrophages is likely to provide sites for binding of factor VII and activation of factor X in vivo during clotting reactions associated with alveolar edema and inflammation.     

Frequency of small-colony variants and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus in cystic fibrosis patients

Background

Small-colony variants (SCVs) are a distinct phenotype of Staphylococcus aureus, known for their role in chronic, difficult to treat infections, including cystic fibrosis (CF) lung disease. The goal of this study was to characterize SCV MRSA infection in an adult and pediatric CF population and to identify antibiotic susceptibility patterns unique to SCV MRSA.

High Risk of New Episode of Symptomatic Vasospasm in Unaffected Arteries in Subarachnoid Hemorrhage Patients Receiving Targeted Endovascular Treatment for Symptomatic Focal Vasospasm

Background

There is controversy whether asymptomatic vasospasm in other arteries should be concurrently treated (global treatment) in patients receiving targeted endovascular treatment [percutaneous-transluminal-angioplasty (PTA) and/or intra-arterial (IA) vasodilators] for focal symptomatic vasospasm.

Objective

To determine the rates of occurrence of new symptomatic vasospasm in previously asymptomatic arterial distributions among patients with aneurysmal subarachnoid hemorrhage (SAH) who underwent targeted endovascular treatment for focal symptomatic vasospasm.

Methods

We identified all patients with SAH who had received targeted endovascular treatment during a 4-year period. We ascertained any new occurrence of symptomatic vasosopasm requiring endovascular treatment in previously unaffected (and untreated) arterial distributions within the same hospitalization. Blinded reviewers quantitatively graded angiographic vasospasm (<25, 26–49, ≥50 %) in all major arteries for each patient at the time of targeted treatment.

Results

Of the 41 patients who received targeted endovascular treatment (PTA in 41 % and vasodilators in 59 %), 11 (27 %) developed new symptomatic vasospasm in previously asymptomatic vascular distributions requiring endovascular treatment. Moderate severity of angiographic vasospasm in asymptomatic arteries at the time of targeted treatment tended to predict the occurrence of new symptomatic vasospasm. The rate of death and disability at discharge [modified Rankin scale (mRS) of 3–6] was 82 % (9/11) among those who developed a new episode of symptomatic vasospasm compared with 70 % (21/30) in those who did not (P = 0.58).

Conclusions

High risk of new occurrence of ischemic symptoms in previously asymptomatic (and untreated) arterial distributions among patients receiving targeted treatment should be recognized. Further studies should evaluate the benefit of performing global endovascular treatment during the initial targeted endovascular treatment session.     

SARS-CoV-2 infection and vaccination trigger long-lived B and CD4+ T lymphocytes with implications for booster strategies

BACKGROUNDImmunization against SARS-CoV-2, the causative agent of COVID-19, occurs via natural infection or vaccination. However, it is currently unknown how long infection- or vaccination-induced immunological memory will last.METHODSWe performed a longitudinal evaluation of immunological memory to SARS-CoV-2 up to 1 year after infection and following mRNA vaccination in naive individuals and individuals recovered from COVID-19 infection.RESULTSWe found that memory cells are still detectable 8 months after vaccination, while antibody levels decline significantly, especially in naive individuals. We also found that a booster injection is efficacious in reactivating immunological memory to spike protein in naive individuals, whereas it was ineffective in previously SARS-CoV-2–infected individuals. Finally, we observed a similar kinetics of decay of humoral and cellular immunity to SARS-CoV-2 up to 1 year following natural infection in a cohort of unvaccinated individuals.CONCLUSIONShort-term persistence of humoral immunity, together with the reduced neutralization capacity versus the currently prevailing SARS-CoV-2 variants, may account for reinfections and breakthrough infections. Long-lived memory B and CD4⁺ T cells may protect from severe disease development. In naive individuals, a booster dose restored optimal anti-spike immunity, whereas the needs for vaccinated individuals who have recovered from COVID-19 have yet to be defined.FUNDINGThis study was supported by funds to the Department of Experimental and Clinical Medicine, University of Florence (Project Excellence Departments 2018–2022), the University of Florence (project RICTD2122), the Italian Ministry of Health (COVID-2020-12371849), and the region of Tuscany (TagSARS CoV 2).     

Trends in pemphigus research over 15 years

Background Although pemphigus is a rare autoimmune blistering disease, it attracts the attention of physicians of many disciplines. Objective This study aims to assess the number of articles on pemphigus that have been published over 15 years in dermatology vs. non‐dermatology medical journals, and to evaluate the quality of available evidence. Methods PubMed was searched for articles on pemphigus published between 1 January 1993 to 31 December 2007 using the search word pemphigus. Articles were characterized by publication type and journal type per year. Regression analysis was used to determine the effect of year of publication on number of publications of each type. Results The search yielded 2032 publications on pemphigus during the evaluation period. Sixty‐one per cent were published in dermatology journals. Overall, the number of publications increased linearly with time. Most of this increase was accounted for by publications in non‐dermatology journals. There was an increase in clinical trials over the course of the study period. The number of certain publications with lower quality of evidence, mainly case reports and letters to the editor, increased significantly in the last few years. There was no increase in publications with high quality of evidence. Conclusions The increase on data from non‐dermatology disciplines is a welcome contribution. Nevertheless, high‐quality evidence on pemphigus is still lacking. We trust that the current trend towards evidence‐based dermatology will impact future research on this severe disease.