Validación del uso de inhibidores sintéticos de la aromatasa en la masculinización de la tilapia Oreochromis niloticus

La tilapia es una de las especies más cultivadas a nivel mundial; sin embargo, es una especie altamente precoz lo que afecta su crecimiento y ocasiona la superpoblación en las unidades de cultivo. Para prevenir este problema existe la opción de cultivar organismos 100% machos. El uso de hormonas es uno de los métodos más utilizados para inducir la masculinización. Actualmente se experimenta con inhibidores de la aromatasa como posibles sustitutos de hormonas esteroides. Existe evidencia de que dichos inhibidores de la aromatasa han logrado un relativo éxito en la reversión sexual en peces. En el presente estudio se evaluó la eficiencia de dos inhibidores como agentes masculinizantes durante la diferenciación sexual de crías de tilapia alimentadas durante 28 días con dietas suplementadas con andrógeno 17-α-metiltestosterona 60 mg/kg (control positivo), letrozol (50, 100 y 200 mg/kg de alimento) y exemestano (1000, 1500 y 2000 mg/kg de alimento) y un grupo control negativo (sin hormonas) en tres experimentos. Se evaluó la supervivencia y el crecimiento y el porcentaje de masculinización en cada experimento. Los resultados muestran que los tratamientos no afecta la supervivencia observándose valores por arriba del 85% de supervivencia en la mayoría de los casos, sin un efecto negativo en el crecimiento de las tilapias. El porcentaje de masculinización presento diferencias significativas entre los inhibidores y el grupo control; se registró un 100% machos en todos los tratamientos experimentales. Se concluye que el suministro de inhibidores sintéticos de la aromatasa son eficientes para lograr poblaciones de tilapia 100% machos

NUEVO REGISTRO DE ESPECIES DE PHILOMETRA COSTA, 1845 (NEMATODA: PHILOMETRIDAE) QUE INFECTAN LA GÓNADA DE HYPORHAMPHUS NAOS BANFORD & COLLETTE, 2001 (HEMIRAMPHIDAE: BELONIFORMES) EN SINALOA, MÉXICO

The objective of this work was to identify the species of parasitic nematodes that infect the gonads of female “birdfish” Hyporhamphus naos Banford & Collette, 2001 (Hemiramphidae: Beloniformes). This species of fish is considered key in terms of the local artisanal fishery index, it is economically transcendental for fishermen and regional consumers who annually wait for its arrival in the bay to be consumed. The nematode Philometra Costa, 1845 (Nematoda: Philometridae) was identified parasitizing the female gonads of H. naos. Two immature female nematodes were found (prevalence 8%, mean abundance 0.08 and mean intensity 1). New information is recorded on the distribution of parasitic nematodes of this genus in this area of ​​the tropical Pacific and a new host. This is the first record of Philometra parasitic on female gonads in H. naos fish in Mexico. The first world record was Philometra longa Moravec, Barton & Shamsi, 2021 in the fish Hyporhamphus australis (Steindachner, 1866) and P. inconveniens Moravec, Barton & Shamsi, 2021 in the fish Hyporhamphus melanochir (Valenciennes, 1847) in Australia. The present study extends the knowledge of the composition by species of the Philometrids that parasitize marine fish. The results of this work contribute to the knowledge on the biology, biodiversity and host preference of these parasites in this fish with great regionalization in the consumption of fish species that present a broad gastronomic social identity in these coastal areas in the port of Mazatlan.El objetivo de este trabajo fue identificar las especies de nemátodos parásitos que infectan a las gónadas en hembras del pez “pajarito” Hyporhamphus naos Banford & Collette, 2001 (Hemiramphidae: Beloniformes). Esta especie de pez se considera clave en términos del índice de pesquería artesanal local, es económicamente transcendental para los pescadores y consumidores regionales que esperan anualmente su arribo a la bahía para ser consumidos.  Se identificó al nematodo Philometra Costa, 1845 (Nematoda: Philometridae) parasitando las gónadas femeninas de H. naos. Se encontraron dos nematodos hembras inmaduras (prevalencia 8%, abundancia media 0,08 e intensidad media 1). Se registra nueva información sobre la distribución de parásitos nematodos de este género en esta zona del Pacífico tropical y un nuevo hospedero. Este es el primer registro de Philometra parásito de las gónadas femeninas en peces H. naos en México. El primer registro mundial fue Philometra longa Moravec, Barton & Shamsi, 2021 en el pez Hyporhamphus australis (Steindachner, 1866) y P. inconveniens Moravec, Barton & Shamsi, 2021 en el pez Hyporhamphus melanochir (Valenciennes, 1847) en Australia. El presente estudio amplía el conocimiento de la composición por especies de los Philométridos que parasitan peces marinos. Los resultados de este trabajo contribuyen al conocimiento en la biología, la biodiversidad y la preferencia del hospedero de estos parásitos en este pez con gran regionalización en el consumo de especies ícticas que presentan amplia identidad social gastronómica en estas zonas costeras en el puerto mazatleco

The clinical and molecular cardiometabolic fingerprint of an exploratory psoriatic arthritis cohort is associated with the disease activity and differentially modulated by methotrexate and apremilast

Objectives: (1) To evaluate clinical and molecular cardiovascular disease (CVD) signs and their relationship with psoriatic arthritis (PsA) features and (2) to identify a clinical patient profile susceptible to benefit from methotrexate (MTX) and/or apremilast regarding CVD risk. Methods: This cross-sectional study included 100 patients with PsA and 100 age-matched healthy donors. In addition, an exploratory cohort of 45 biologically naïve patients treated for 6 months with apremilast, MTX or combined therapy according to routine clinical practice was recruited. Extensive clinical and metabolic profiles were obtained. Ninety-nine surrogate CVD-related molecules were analysed in plasma and peripheral blood mononuclear cells (PBMCs). Hard cluster analysis was performed to identify the clinical and molecular phenotypes. Mechanistic studies were performed on adipocytes. Results: Cardiometabolic comorbidities were associated with disease activity and long-term inflammatory status. Thirty-five CVD-related proteins were altered in the plasma and PBMCs of PsA patients and were associated with the key clinical features of the disease. Plasma levels of some of the CVD-related molecules might distinguish insulin-resistant patients (MMP-3, CD163, FABP-4), high disease activity (GAL-3 and FABP-4) and poor therapy outcomes (CD-163, LTBR and CNTN-1). Hard cluster analysis identified two phenotypes of patients according to the rates of cardiometabolic comorbidities with distinctive clinical and molecular responses to each treatment. Conclusions: (1) Novel CVD-related proteins associated with clinical features could be emerging therapeutic targets in the context of PsA and (2) the pleiotropic action of apremilast could make it an excellent choice for the management of PsA patients with high CVD risk, targeting metabolic alterations and CVD-related molecules

Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context

Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols

Switching TNF antagonists in patients with chronic arthritis: An observational study of 488 patients over a four-year period

The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34-0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97-2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13-4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications. © 2006 Gomez-Reino and Loreto Carmona; licensee BioMed Central Ltd