Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19.

Plitidepsin, a marine-derived cyclic-peptide, inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A. Here, we show that plitidepsin distributes preferentially to lung over plasma, with similar potency against across several SARS-CoV-2 variants in preclinical studies. Simultaneously, in this randomized, parallel, open-label, proof-of-concept study (NCT04382066) conducted in 10 Spanish hospitals between May and November 2020, 46 adult hospitalized patients with confirmed SARS-CoV-2 infection received either 1.5 mg (n = 15), 2.0 mg (n = 16), or 2.5 mg (n = 15) plitidepsin once daily for 3 d. The primary objective was safety; viral load kinetics, mortality, need for increased respiratory support, and dose selection were secondary end points. One patient withdrew consent before starting procedures; 45 initiated treatment; one withdrew because of hypersensitivity. Two Grade 3 treatment-related adverse events were observed (hypersensitivity and diarrhea). Treatment-related adverse events affecting more than 5% of patients were nausea (42.2%), vomiting (15.6%), and diarrhea (6.7%). Mean viral load reductions from baseline were 1.35, 2.35, 3.25, and 3.85 log10 at days 4, 7, 15, and 31. Nonmechanical invasive ventilation was required in 8 of 44 evaluable patients (16.0%); six patients required intensive care support (13.6%), and three patients (6.7%) died (COVID-19-related). Plitidepsin has a favorable safety profile in patients with COVID-19.

Heterogeneity of pollen food allergy syndrome in seven Southern European countries: The @IT.2020 multicenter study.

BACKGROUND: Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. OBJECTIVES: To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. METHODS: As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. RESULTS: Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). CONCLUSIONS: PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics.

"Whole" vs. "fragmented" approach to EAACI pollen season definitions: A multicenter study in six Southern European cities.

BACKGROUND: The adequate definition of pollen seasons is essential to facilitate a correct diagnosis, treatment choice, and outcome assessment in patients with seasonal allergic rhinitis. A position paper by the European Academy of Allergy and Clinical Immunology (EAACI) proposed season definitions for Northern and Middle Europe. OBJECTIVE: To test the pollen season definitions proposed by EAACI in six Mediterranean cities for seven pollen taxa. METHODS: As part of the @IT.2020 multi-center study, pollen counts for Poaceae, Oleaceae, Fagales, Cupressaceae, Urticaceae (Parietaria spp.), and Compositae (Ambrosia spp., Artemisia spp.) were collected from January 1 to December 31, 2018. Based on these data, pollen seasons were identified according to EAACI criteria. A unified monitoring period for patients in AIT trials was created and assessed for feasibility. RESULTS: The analysis revealed a great heterogeneity between the different locations in terms of pattern and length of the examined pollen seasons. Further, we found a fragmentation of pollen seasons in several segments (max. 8) separated by periods of low pollen counts (intercurrent periods). Potential monitoring periods included often many recording days with low pollen exposure (max. 341 days). CONCLUSION: The Mediterranean climate leads to challenging pollen exposure times. Monitoring periods for AIT trials based on existing definitions may include many intermittent days with low pollen concentrations. Therefore, it is necessary to find an adapted pollen season definition as individual solution for each pollen and geographical area.

Pediatric asthma: An unmet need for more effective, focused treatments.

BACKGROUND: Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. METHODS: A two-day, face-to-face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. RESULTS: These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non-steroid-based alternative therapies in patients <6 years of age. An increased focus on children is needed in the context of clinical practice guidelines for asthma; current pediatric practice relies mostly on extrapolations from adult recommendations. Furthermore, no uniform definition of pediatric asthma exists, which hampers timely and robust diagnosis of the condition in affected patients. CONCLUSIONS: There is a need for a uniform definition of pediatric asthma, clearly distinguishable from adult asthma. Furthermore, guidelines which provide specific treatment recommendations for the management of pediatric asthma are also needed. Clinical trials and real-world evidence studies assessing anti-immunoglobulin E (IgE) therapies and other monoclonal antibodies in children <6 years of age with asthma may provide further information regarding the most appropriate treatment options in these vulnerable patients. Early intervention with anti-IgE and non-steroid-based alternative therapies may delay disease progression, leading to improved clinical outcomes.

Anti-inflammatory activity of Penstemon gentianoides and Penstemon campanulatus.

CONTEXT: Penstemon gentianoides (Kunth) Poir. and Penstemon campanulatus (Cav.) Willd. (Plantaginaceae) are important medicinal plants in Mexico used by indigenous people for their anti-inflammatory effects and to also reduce rheumatic pains. OBJECTIVE: In addition to radical scavenging activity, the anti-inflammatory activity of the extracts, fractions and compounds of these plants were investigated and reported here for the first time. MATERIALS AND METHODS: The anti-inflammatory activities of MeOH, CH(2)Cl(2), and ethyl acetate extracts and iridoid, flavonoids, and phenylpropanoids from Penstemon gentianoides and P. campanulatus were studied in the TPA-induced mouse ear edema model. In addition, antioxidant activity against DPPH, crocin and ß-carotene were investigated. RESULTS: All extracts were tested and a selection of known compounds significantly (p <0.05) inhibited mouse ear edema. The results showed that CH(2)Cl(2) extracts of roots and stems from P. gentianoides and ethyl acetate extracts of leaves from P. gentianoides and P. campanulatus, as well as luteolin, diosmetin, penstemide and verbascoside produced the most positive results. Of all substances tested, the CH(2)Cl(2) extract of P. gentianoides roots was the most powerful inhibitor (ED(50)=0.07 mg/ear), with activity comparable to that of indomethacin. These extracts, compounds purified, as well as known compounds, inhibited oxidation of ß-carotene and crocin. DISCUSSION AND CONCLUSION: These findings showed that the iridoid monoterpenes, flavonoids and phenylpropanoids present in these plants species may all contribute to the observed anti-inflammatory activity. Additionally, the observed antioxidant activity is correlated with the anti-inflammatory activity of these plants and the phytochemicals derived from them.

Antioxidant activities of extracts from Barkleyanthus salicifolius (Asteraceae) and Penstemon gentianoides (Scrophulariaceae).

Various extracts of the aerial parts of Barkleyanthus salicifolius (Asteraceae) and Penstemon gentianoides (Scrophulariaceae) have been used in folk medicine to treat many ailments, particularly inflammation and migraine. Neither the bioactive components responsible nor the mechanisms involved have been evaluated. Here are reported antioxidant activities of their methanol, dichloromethane, and ethyl acetate extracts. Samples were evaluated for oxygen radical absorption capacity (ORAC), ferric reducing antioxidant power (FRAP), 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging, and inhibition of the formation of thiobarbituric acid reactive species (TBARS), a measure of lipid peroxidation. Antioxidant activities were strongly correlated with total polyphenol content. The most active extracts from P. gentianoides in scavenging DPPH radicals and inhibiting TBARS formation were the methanol extract (A) and a further ethyl acetate extract of this (E). Partition E was further divided into eight fractions, and both E and the fractions were compared for activity against butylated hydroxytoluene, quercetin, and tocopherol. Partition E and the most active fractions, 5 and 6, were found to have I(50) values of 14.1, 38.6, and 41.8 ppm, respectively, against DPPH and 18.5, 26.0, and 12.7 ppm, respectively, against TBARS formation. Consistent with this finding, partition E and fractions 4-6 had the greatest ORAC and FRAP values. These results show that these plants could be useful antioxidant sources.

Efectos del aloe barbadensis sobre las lesiones y la secreción gástricas producidas por etanol y estrés en ratas / Effect of aloe barbadensis on lesions and gastric secretion produced by ethanol and stress in rats

Se estudia el efecto de extractos de Aloe barbadensis sobre las lesiones gástricas producidas por 2 modelos de úlcera gástrica experimental en ratas. Se usaron 2 extractos, uno preparado en dosis de 10 y 20 mg y otro preparado en dosis de 12,5 y 25 mg sobre las lesiones gástricas producidas por los modelos de etanol y de estrés por inmovilización más frio. También se estudió la secreción gástrica. Las dosis de 20 mg produjo frente al efecto dañino del etanol una discreta disminuciòn del número de lesiones así como una disminuciòn significativa del índice de lesión. La administración de las dosis de 25 mg provocó frente al daño del etanol una disminucion significativa, tanto del número como de la severidad de las lesiones. La dosis de 12,5 mg no protegió a la mucosa de la acción del etanol. La administración por vía intraperitoneal de este extracto no protegió la mucosa gástrica del daño producido por el estrés por inmovilización más frio y produjo una disminuciòn de la acidez total y un aumento del pH del jugo gástrico significativos, mientras que la administraciòn por vía oral produjo una disminuciòn significativa tanto del número de lesiones como del índice de lesión y no ocasionó modificaciones en la secreción gástrica

Efectos del aloe barbadensis sobre las lesiones y la secreción gástricas producidas por etanol y estrés en ratas / Effect of aloe barbadensis on lesions and gastric secretion produced by ethanol and stress in rats

Se estudia el efecto de extractos de Aloe barbadensis sobre las lesiones gástricas producidas por 2 modelos de úlcera gástrica experimental en ratas. Se usaron 2 extractos, uno preparado en dosis de 10 y 20 mg y otro preparado en dosis de 12,5 y 25 mg sobre las lesiones gástricas producidas por los modelos de etanol y de estrés por inmovilización más frio. También se estudió la secreción gástrica. Las dosis de 20 mg produjo frente al efecto dañino del etanol una discreta disminuciòn del número de lesiones así como una disminuciòn significativa del índice de lesión. La administración de las dosis de 25 mg provocó frente al daño del etanol una disminucion significativa, tanto del número como de la severidad de las lesiones. La dosis de 12,5 mg no protegió a la mucosa de la acción del etanol. La administración por vía intraperitoneal de este extracto no protegió la mucosa gástrica del daño producido por el estrés por inmovilización más frio y produjo una disminuciòn de la acidez total y un aumento del pH del jugo gástrico significativos, mientras que la administraciòn por vía oral produjo una disminuciòn significativa tanto del número de lesiones como del índice de lesión y no ocasionó modificaciones en la secreción gástrica

Tamizaje antitumoral de plantas cubanas: II; estudio preliminar / Antitumorous screening of cuban plants: II; preliminary study

Los extractos etanólicos de 17 especies botánicas, fueron testados frente a los tumores experimentales leucemia P-388 y adenocarcinoma mamario 755. De estas especies, 16 pertenecen a la familia Rubiaceae y la restante a la familia Clusiaceae; 9 son endémicas. No se observó actividad antitumoralsignificativa de los extractos ensayados con las dosis administradas

Tamizaje antitumoral de plantas cubanas. II; estudio preliminar / Antituorous screening of cuban plants: II; preliminary study

Los extractos etanólicos de 17 especies botánicas, fueron testados frente a los tumores experimentales leucemia P-388 y adenocarcinoma mamario 755. De estas especies, 16 pertenecen a la familia Rubiaceae y la restante a la familia Clusiaceae; 9 son endémicas. No se observó actividad antitumoralsignificativa de los extractos ensayados con las dosis administradas

Efectos del aloe aplicado como inyectable contra el dolor / Effects of aloe applied as injectable agent against pain

Se obtíene aloe de las hojas del Aloe barbadensis Miller Liliaceae. Se preparan inyectables de concentración 10 mg/ml y se aplican en 23 pacientes con neuralgias, cefaleas, plexitis y dolores oculares, cuyo resultado son 76,3

con desaparición total del dolor de los pacientes tratados con aloe a razón de l ml/día (AU)

Efectos del aloe aplicado como ungüento en la radiodermitis / Effects of aloe applied as ointent in radiodermatitis

De las hojas del Aloe barbadensis Miller Liliaceae, se obtuvo el Aloe, que fue preparado en forma de ungüento hidrófilo y aplicado a 52 pacientes oncológicos con radiodermitis húmeda y seca. El resultado fue de 57,6

fueron curados totalmente a la semana, 26,9

a las dos semanas y el 7,7

para 3ra. y 4ta. semanas (AU)

Efectos del aloe aplicado como ungüento en la radiodermitis / Effects of aloe applied as ointment in radiodermatitis

De las hojas del Aloe barbadensis Miller Liliaceae, se obtuvo el Aloe, que fue preparado en forma de ungüento hidrófilo y aplicado a 52 pacientes oncológicos con radiodermitis húmeda y seca. El resultado fue de 57,6% fueron curados totalmente a la semana, 26,9% a las dos semanas y el 7,7% para 3ra. y 4ta. semanas

Efectos del aloe aplicado como inyectable contra el dolor / Effects of aloe applied as injectable agent against pain

Se obtíene aloe de las hojas del Aloe barbadensis Miller Liliaceae. Se preparan inyectables de concentración 10 mg/ml y se aplican en 23 pacientes con neuralgias, cefaleas, plexitis y dolores oculares, cuyo resultado son 76,3% con desaparición total del dolor de los pacientes tratados con aloe a razón de l ml/día

Tamizaje antitumoral de la flora de Cuba. estudio preliminar / Antituoral screening of the Cuban flora: preliminary study

Se ensayan extractos etanólicos de las hojas y los tallos de 15 especies botánicas en los tumores experimentales: leucemia P-388 y L-1210 y adenocarcinoma mamario 755. Se analiza que estas especies pertencen a las familias Rubiaceae, Solanaceae y Boraginaceae, y de éstas, 11 son endémicas. Se informa que 2 especies, Acrosynanthus revolutus y Palicourea domingensis (Rubiaceae), muestran actividad antitumoral moderada frente a estas enfermedades (AU)

Tamizaje antitumoral de la flora de Cuba: estudio preliminar / Antitumoral screening of the Cuban flora: preliminary study

Se ensayan extractos etanólicos de las hojas y los tallos de 15 especies botánicas en los tumores experimentales: leucemia P-388 y L-1210 y adenocarcinoma mamario 755. Se analiza que estas especies pertencen a las familias Rubiaceae, Solanaceae y Boraginaceae, y de éstas, 11 son endémicas. Se informa que 2 especies, Acrosynanthus revolutus y Palicourea domingensis (Rubiaceae), muestran actividad antitumoral moderada frente a estas enfermedades

Ensayos preliminares de los efectos antitumorales del principio activo de la Solanda longiflora. TUS. Solanaceas / Preliminary assays of the antitumor effects of the Solanda longiflora TUS. Solanaceae active principle

Se señala que las hojas y tallos de la S. longiflora fueron tratados con cinco sistemas de solventes cuyos extractos fueron ensayados en los tumores experimentales de los animales: leucemia 1 210, carcinoma de pulmón de Lewis y melanoma de Harding-Pasey. Los resultados fueron significativos para los sistemas IV y V y para los tumores: carcinoma de Lewis y melanoma de Harding-Pasey(AU)

Los efectos antitumorales de los tallos, hojas y flores del Abutilon hirstum (LAM) SW. Malvaceae / Antitumor effects of Abutilon hirstum (LAM) SW. Malvaceae stems, leaves and flowers

Se obtienen fracciones de hojas, flores y tallos del A. hirstum, las cuales fueron procesadas y extraídas por mezcla de solventes de donde se lograron preparaciones que fueron ensayadas con tumores experimentales en varias dosis y vías. Los tumores ensayados son: sarcoma 180, sarcoma 37, adenocarcinoma mamario 755 y melanoma de Harding Pasey, todos en ratones machos. Estas fracciones demuestran actividad antitumoral y mayor efectividad en los sarcomas 37 y 180 que en el resto de los tumores(AU)

Efectos antitumorales de la fracción purificada de las hojas del Erythroxylon alaternifolium A. Rich. y Erythroxylon pedicellare (GRISEB) O. E. Schulz / Antitumor effects of the purified fraction from Erythroxylon alaternifolium A. Rich and Erythroxylon pedicellare (GRISEB) O. E. Schulz leaves

Se ensaya una fracción purificada obtenida de las hojas de E. alaternifolium y E. pedicellare en los tumores experimentales siguientes: carcinoma de Ehrlich, sarcoma 180, melanoma de Harding Pasey, hepatoma 22 y leucemia 1210, todos en ratones, el carcinosarcoma de Walker y el carcinoma de Ehrlich(AU)

Fracciones de las hojas del orthosiphon stamineus beth con actividad antitumoral. Resultados preliminares / Fractions of Orthosiphon stamineus beth leaves with antitumor activity. Preliminary results

Fueron ensayadas fracciones obtenidas de las hojas del O. stamineus de la familia de las Labiatae, introducidas y cultivadas en Cuba, con los tumores experimentales hepatoma 22, adenocarcinoma mamario 755, melanoma de Harding Pasey y leucemia 1 210; además ensayamos en bacterias para medir su actividad antibiótica con el Staphylococcus aureus, Bacilus subtilis y Escherichia coli. La fracción con mayor efectividad fue con el melanoma de Harding Pasey(AU)