Efficacy and safety of intravenous fosphenytoin for patients with acute herpes zoster-associated pain: A placebo-controlled randomized trial.

Acute zoster-associated pain develops in most patients with herpes zoster. Nonopioid analgesics are usually used to treat acute zoster-associated pain but are frequently ineffective. We administered intravenous fosphenytoin, the prodrug of phenytoin, to patients with acute zoster-associated pain to examine its analgesic efficacy and safety. At 13 medical institutions in Japan, we conducted a phase II, double-blind, placebo-controlled, randomized trial of intravenous fosphenytoin in Japanese inpatients with acute zoster-associated pain for whom nonopioid analgesics had shown an insufficient analgesic effect. The patients were randomly assigned (1:1:1) to receive a single intravenous dose of fosphenytoin at 18 mg/kg (high dose), a single intravenous dose of fosphenytoin at 12 mg/kg (low dose), or placebo. The primary endpoint was the mean change per hour (slope) in the numerical rating scale score from the baseline score until 120 min after dosing. Seventeen patients were randomly assigned to the low-dose fosphenytoin group (n = 6, median age 62.5 years, range 39-75 years), high-dose fosphenytoin group (n = 5, median age 69.0 years, range 22-75 years), and placebo group (n = 5, median age 52.0 years, range 38-72 years). One patient was excluded because of investigational drug dilution failure. This study was discontinued because of the influences of coronavirus disease 2019. The slope was significantly lower in the high- and low-dose fosphenytoin groups than in the placebo group (P < 0.001 and P = 0.016, respectively). Responsiveness to intravenous fosphenytoin (≥2-point reduction in the numerical rating scale score from baseline to 120 min after dosing) was inferred at plasma total phenytoin concentrations of 10-15 µg/mL. Treatment-emergent adverse events caused no safety concerns in the clinical setting and intravenous fosphenytoin was well tolerated. Intravenous fosphenytoin appears to be an effective and promising alternative treatment for acute zoster-associated pain. Trial Registration: ClinicalTrials.gov NCT04139330.

"Live-Autoradiography" Technique Reveals Genetic Variation in the Rate of Fe Uptake by Barley Cultivars.

Iron (Fe) is an essential trace element in plants; however, the available Fe in soil solution does not always satisfy the demand of plants. Genetic diversity in the rate of Fe uptake by plants has not been broadly surveyed among plant species or genotypes, although plants have developed various Fe acquisition mechanisms. The "live-autoradiography" technique with radioactive 59Fe was adopted to directly evaluate the uptake rate of Fe by barley cultivars from a nutrient solution containing a very low concentration of Fe. The uptake rate of Fe measured by live autoradiography was consistent with the accumulation of Fe-containing proteins on the thylakoid membrane. The results revealed that the ability to acquire Fe from the low-Fe solution was not always the sole determinant of tolerance to Fe deficiency among barley genotypes. The live-autoradiography system visualizes the distribution of ß-ray-emitting nuclides and has flexibility in the shape of the field of view. This technique will strongly support phenotyping with regard to the long-distance transport of nutrient elements in the plant body.

Serum interleukin-22 and vascular endothelial growth factor serve as sensitive biomarkers but not as predictors of therapeutic response to biologics in patients with psoriasis.

The T-helper (Th)17 cell plays a crucial role in the pathogenesis of psoriasis, and several biological therapies have shown to be highly efficient in the treatment. However, some patients respond poorly to these therapies and may even develop paradoxical adverse effects. To evaluate the significance of serum immunological factors or circulating competent cells for biomarkers or predictors to biological therapies, we retrospectively analyzed 28 patients with psoriasis (19 psoriasis vulgaris, three pustular psoriasis and six psoriasis arthropathica). The numbers of patients treated with each agents were 16 for ustekinumab, six for adalimumab and six for infliximab. Patients were classified into three types according to the responsiveness: 13 patients were high-responders showing a 75% or more reduction of Psoriasis Area and Severity Index (PASI); 10 patients were moderate-responders showing PASI reduction of less than 75%; and five patients were non-responders showing PASI elevation. During the treatments, serum levels of interleukin (IL)-22 and vascular endothelial growth factor (VEGH) [corrected] were monitored. At baseline, serum IL-22 levels were significantly higher in the psoriatic patients than the normal controls. Both serum IL-22 and VEGF levels significantly correlated with PASI. After the treatment, the high-responders showed significant decreases in serum IL-22 and VEGF. On the other hand, serum IL-22 levels in the non-responders were elevated. However, the baseline levels of serum IL-22 and VEGF were not significantly different between the three groups. These results suggest that serum IL-22 and VEGF levels serve as sensitive biomarkers but not as predictors of therapeutic response to biologics in patients with psoriasis.