Two years follow-up of relapsing eosinophilic pneumonia with concomitant severe asthma successfully treated with benralizumab: A case report and brief review of the literature.

Relapsing eosinophilic pneumonia and severe eosinophilic asthma are rare and disabling diseases, which share common inflammatory backgrounds and often require long-term systemic steroid therapy. Benralizumab is a humanized antibody targeting IL-5 receptor that reduces corticosteroid dependence and flares up in severe eosinophilic asthma on long term. In this case report, successful treatment of eosinophilic pneumonia and severe eosinophilic asthma with benralizumab is described after a 2-year follow up, showing the promising results of this therapy for eosinophilic pneumonia management.

Global assessment of oil and gas methane ultra-emitters.

Methane emissions from oil and gas (O&G) production and transmission represent a considerable contribution to climate change. These emissions comprise sporadic releases of large amounts of methane during maintenance operations or equipment failures not accounted for in current inventory estimates. We collected and analyzed hundreds of very large releases from atmospheric methane images sampled by the TROPOspheric Monitoring Instrument (TROPOMI) between 2019 and 2020. Ultra-emitters are primarily detected over the largest O&G basins throughout the world. With a total contribution equivalent to 8 to 12% (~8 million metric tons of methane per year) of the global O&G production methane emissions, mitigation of ultra-emitters is largely achievable at low costs and would lead to robust net benefits in billions of US dollars for the six major O&G-producing countries when considering societal costs of methane.

Sensitization to Gibberellin-Regulated Protein (Peamaclein) Among Italian Cypress Pollen-Sensitized Patients.

BACKGROUND AND OBJECTIVES: Peach gibberellin-regulated protein (peamaclein) has recently emerged as a relevant food allergen in cypress pollen-hypersensitive patients. Objective: We investigated monosensitization to peamaclein among Italian cypress pollen-allergic patients. MATERIAL AND METHODS: A total of 835 cypress pollen-hypersensitive patients from 28 Italian allergy centers underwent a thorough work-up to determine food-allergic reactions and performed skin prick testing with a commercial peach extract containing peamaclein. IgE to rPru p 3 was measured in peach reactors, and those with negative results were enrolled as potentially monosensitized to peamaclein. IgE reactivity to rPru p 7 was evaluated using immunoblot and an experimental ImmunoCAP with rPru p 7. RESULTS: Skin prick tests were positive to peach in 163 patients (19.5%); however, 127 (77.9%) were excluded because they reacted to Pru p 3. Twenty-four patients (14.7%) corresponding to 2.8% of the entire study population) were considered potentially monosensitized to peamaclein. No geographic preference was observed. Seventeen of the 24 patients (70.8%) had a history of food allergy, mainly to peach (n=15). Additional offending foods included other Rosaceae, citrus fruits, fig, melon, tree nuts, and kiwi. On peach immunoblot, only 3 of 18 putative peamaclein-allergic patients reacted to a band at about 7 kDa; an additional 4 patients reacted at about 50-60 kDa. Ten of 18 patients (56%) had a positive result for Pru p 7 on ImmunoCAP. CONCLUSION: Allergy and sensitization to peamaclein seem rare in Italy. Most patients react to peach, although other Rosaceae fruits and several citrus fruits may also be offending foods. Peach and cypress pollen probably also share cross-reacting allergens other than peamaclein.

Observational prospective study comparing mucoactive and antibiotic treament in the management of acute cough from upper respiratory tract infections.

AIM: Since the efficacy of antibiotics in the management of cough from upper respiratory tract infections (URTI) is unclear, we conducted an observational study to evaluate the efficacy of antibiotic compared to symptomatic treatment in adults with productive cough from URTI in a real life setting. METHODS: One-hundred and 50 subjects presenting to five general practice ambulatories with productive cough due to URTI were included in the study. According to the physician judgment, patients were treated with either oral antibiotics (group A, 50 patients), a mucoactive syrup (sobrerol: group S, 50 patients) as symptomatic treatment, or both sobrerol and oral antibiotics (group SA, 50 patients). Cough severity was assessed daily with a diary, by means of a validated verbal category-descriptive (VCD) Scale. RESULTS: In every treatment group cough severity decreased over time (P<0.001); however, during the first week of treatment patients in groups S and SA experienced significantly lower VCD score values in comparison to Group A (P=0.045 and P=0.010, respectively). On the other hand, the VCD score was never significantly different between the two groups that received symptomatic treatment at any of the 4 weeks of the study, suggesting that the effect observed was due to the action of the mucoactive syrup. CONCLUSION: Our data confirm the lack of efficacy of antibiotics in the management of productive cough in URTI and suggest that symptomatic treatment should be preferred to antibiotics in acute cough from URTI.

Multiple pathways of Pb(2+) permeation in rat cerebellar granule neurones.

The pathways of lead (Pb(2+)) uptake were studied in fura-2-loaded cerebellar granule cells from 8-day-old rats. In a nominal Ca-free external bath, Pb(2+) (5-50 microM) determined an increase of the fluorescence emission ratio (R = E(340)/E(380)) even in the absence of any specific stimulus. This rise was dose-dependent, was not significantly affected by mM Mg(2+) or Ca(2+), but it was readily reversed by the membrane-permeant heavy metal chelator tetrakis(2-pyridylmethyl) ethylene-diamine (TPEN, 100 microM), indicating that it was due to Pb(2+) influx. The rate of rise, dR/dt, was increased up to a factor of 5 by depolarizing high-KCl solution, indicating a sizeable permeation through voltage-dependent channels. This effect was neither antagonized by nimodipine, nor enhanced by BayK8644, but it was slackened by omega-agatoxin IVA (200 nM), suggesting an involvement of non-L-type calcium channels. Pb(2+) influx was also stimulated by glutamic acid or NMDA in the presence of 10-30 microM glycine, but only in Mg-free solution, suggesting that glutamate channels of the NMDA type are an additional pathway of Pb(2+) uptake. Pb(2+) caused a time-, dose- and stimulus-dependent saturation of the dye, whose intracellular concentration is approximately 10 microM, indicating that intracellular Pb(2+) can readily reach a concentration in the micromolar range. These results indicate that the particular vulnerability of neurones to Pb(2+) poisoning is linked to the presence of specific transport systems, which mediate the rapid uptake of Pb(2+) into the neurone.

Lead inhibition of NMDA channels in native and recombinant receptors.

NMDA channels are key targets for lead (Pb2+) neurotoxicity and Pb2+-induced inhibition of NMDA current is age- and subunit-dependent. In rat cerebellar granule cells maintained in high KCl, glycine affinity as well as sensitivity to ifenprodil change significantly with the days in vitro, indicating a reduction of NR2B subunit expression. Pb2+ blocked NMDA current with IC50 approximately 4 microM and this effect decreased significantly during the second week in vitro. In Xenopus laevis oocytes expressing recombinant NR1-NR2A, NR1-NR2B or NR1-NR2C receptors, Pb2+ inhibited glutamate-activated currents with IC50 of 3.3, 2.5 and 4.7 microM respectively. These data indicate that Pb2+ action is dependent on subunit composition and suggest that down-regulation of the NR2B subunit is correlated to a diminished sensitivity to Pb2+ inhibition.