Palonosetron for the prevention of chemotherapy-induced nausea and vomiting: approval and efficacy

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient characteristics (female gender, younger age, low alcohol consumption, history of motion sickness) are the major risk factors for CINV. This review provides a detailed description of palonosetron, a second-generation 5-hydroxytryptamine 3 (5-HT3) receptor antagonist. The chemistry and pharmacology of palonosetron are described, as well as the initial and recent clinical trials. Palonosetron has a longer half-life and a higher binding affinity than the first-generation 5-HT3 receptor antagonists. Palonosetron has been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. In recent studies, compared to the first-generation 5-HT3 receptor antagonists, palonosetron in combination with dexamethasone demonstrated better control of delayed CINV in patients receiving highly emetogenic chemotherapy. There were no clinically relevant adverse reactions reported in the palonosetron clinical trials which were different from the common reactions reported for the 5-HT3 receptor antagonist class. Due to its efficacy in controlling both acute and delayed CINV, palonosetron may be very effective in the clinical setting of multiple-day chemotherapy and bone marrow transplantation

Lipid composition of pea (Pisum sativum L.) and maize (Zea mays L.) root plasma membrane and membrane-bound peroxidase and superoxide dismutase

Plasma membrane was isolated from roots of pea and maize plants and used to analyze POD and SOD isoforms, as well as lipid composition. Among lipids, phospholipids were the main lipid class, with phosphatidylcholine being the most abundant individual component in both pea and maize plasma membranes. Significant differences between the two plant species were found in the contents of cerebrosides, free sterols, and steryl glycosides. Most maize POD isoforms were with neutral and anionic pI values, but the opposite was observed in pea. While both anionic and cationic SOD isoforms were isolated from maize, only two anionic SOD isoforms were detected in pea

Foliar nutrient resorption patterns of four functional plants along a precipitation gradient on the Tibetan Changtang Plateau

Nutrient resorption from senesced leaves as a nutrient conservation strategy is important for plants to adapt to nutrient deficiency, particularly in alpine and arid environment. However, the leaf nutrient resorption patterns of different functional plants across environmental gradient remain unclear. In this study, we conducted a transect survey of 12 communities to address foliar nitrogen (N) and phosphorus (P) resorption strategies of four functional groups along an eastward increasing precipitation gradient in northern Tibetan Changtang Plateau. Soil nutrient availability, leaf nutrient concentration, and N:P ratio in green leaves ([N:P]g) were linearly correlated with precipitation. Nitrogen resorption efficiency decreased, whereas phosphorus resorption efficiency except for sedge increased with increasing precipitation, indicating a greater nutrient conservation in nutrient-poor environment. The surveyed alpine plants except for legume had obviously higher N and P resorption efficiencies than the world mean levels. Legumes had higher N concentrations in green and senesced leaves, but lowest resorption efficiency than nonlegumes. Sedge species had much lower P concentration in senesced leaves but highest P resorption efficiency, suggesting highly competitive P conservation. Leaf nutrient resorption efficiencies of N and P were largely controlled by soil and plant nutrient, and indirectly regulated by precipitation. Nutrient resorption efficiencies were more determined by soil nutrient availability, while resorption proficiencies were more controlled by leaf nutrient and N:P of green leaves. Overall, our results suggest strong internal nutrient cycling through foliar nutrient resorption in the alpine nutrient-poor ecosystems on the Plateau. The patterns of soil nutrient availability and resorption also imply a transit from more N limitation in the west to a more P limitation in the east Changtang. Our findings offer insights into understanding nutrient conservation strategy in the precipitation and its derived soil nutrient availability gradient

Cross-immunization against respiratory coronaviruses may protect children from SARS-CoV2: more than a simple hypothesis?

In January 2020, a new coronavirus was identified as responsible for a pandemic acute respiratory syndrome. The virus demonstrated a high infectious capability and not-neglectable mortality in humans. However, similarly to previous SARS and MERS, the new disease COVID-19 caused by SARS-CoV-2 seemed to relatively spare children and younger adults. Some hypotheses have been proposed to explain the phenomenon, including lower ACE2 expression in children, cross-immunization from measles/rubella/mumps and BCG-vaccination, as well as the integrity of respiratory mucosa. Herein, we hypothesize that an additional mechanism might contribute to children\u2019s relative protection from SARS-CoV-2, the cross-immunization conferred by previous exposures to other common respiratory coronaviruses. To support our hypothesis, we show a statistically significant similarity in genomic and protein sequences, including epitopes for B- and T-cell immunity, of SARS-CoV-2 and the other beta coronaviruses. Since these coronaviruses are highly diffused across pediatric populations, cross-reactive immunity might reasonably induce an at least partial protection from SARS-CoV-2 in children

Transcriptional Analysis of Lennert Lymphoma Reveals a Unique Profile and Identifies Novel Therapeutic Targets

Lennert lymphoma (LL) is a lymphoepithelioid morphological variant of peripheral T-cell lymphoma—not otherwise specified (PTCL/NOS), clinically characterized by better prognosis if compared with other PTCL/NOS. Although well characterized as far as morphology and phenotype are concerned, very little is known regarding its molecular features. In this study, we investigated the transcriptional profile of this tumor aiming 1) to identify its cellular counterparts; 2) to better define its relation with other PTCLs—and, therefore, its possible position in lymphoma classification; and 3) to define pathogenetic mechanisms, possibly unveiling novel therapeutic targets. To address these issues, we performed gene and microRNA expression profiling on LL and other PTCL/NOS cases; we identified different genes and microRNAs that discriminated LL from other PTCL/NOS. Particularly, LL revealed a molecular signature significantly enriched in helper function and clearly distinguishable from other PTCL/NOS. Furthermore, PI3K/Akt/mTOR pathway emerged as novel potential therapeutic target. In conclusion, based on the already known particular morphological and clinical features, the new molecular findings support the hypothesis that LL might be classified as a separate entity. Preclinical and clinical studies testing the efficacy of PI3K/MTOR inhibitors in this setting are warranted

Grano ed eccesso di rame: può il tocoferolo inibire l'azione della fosfolipasi A?

Piante di grano (Triticum durum cv. Adamello) sono state incubate in una soluzione contenente CuSO4 100 μM per differenti periodi di tempo (da 1 a 960 minuti). Le radici già dopo 1 min di incubazione hanno presentato un aumento del contenuto di rame. In corrispondenza del contenuto massimo degli isomeri del tocoferolo è stato registrato un minimo livello dei lisati dei fosfolipidi, conseguenza di una disattivazione della fosfolipasi A2 (PLA2), enzima in grado di catalizzare l’idrolisi del legame sn-2 acil estere dei glicerofosfolipidi formando lisofosfolipidi ed acidi grassi liberi

Oxidative stress in cerebral small vessel disease dizziness patients, basally and after polyphenol compound supplementation

Leukoaraiosis (LA) is a common radiological finding in elderly, frequently associated with several clinical disorders, including unexplained dizziness. The pathogenesis of LA is multifactorial, with a dysfunction of cerebral microcirculation resulting in chronic hypoperfusion and tissue loss, with oxidative stress involved in this cascade. The aim of this study was to analyse some oxidative stress biomarkers in a cohort of LA patients. In a subgroup of 33 patients with LA and unexplained dizziness, we have then performed an open study to evaluate if 60-day supplementation with a poliphenol compound may modify these biomarkers and influence quality of life, analysed with the Dizziness handicap Inventory (DHI) scale. At baseline, blood oxidative stress parameters values were outside normal ranges and compared to matched healthy controls. After the two months supplementation, we observed a significant decrement of advanced oxidation protein products values and a significant improvement of DHI. Oxidative stress biomarkers may be useful to detect redox imbalance in LA and to provide non-invasive tools to monitor disease status and response to therapy

Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting

BACKGROUND We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy. METHODS In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3–receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide–doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point. RESULTS In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P = 0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P = 0.002), and the overall 120-hour period (37% vs. 22%, P = 0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P = 0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2. CONCLUSIONS Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.