Efecto agudo del carbofuran en juveniles de Chirostoma humboldtianum (Valenncienes 1835) (Atheriniformes: Atherinopsidae)

Background: Chirostoma populations have diminished because of loss of their habitat, introduction of exotic species and pollution. Chirostoma humboldtianum (Valenciennes, 1835) was recorded in Mexico basin, for last time in 1957. Carbofuran is a carbamic inseticide, broad spectrum systemic; its use is prohibited in many countries. However, in Mexico, it is widely used and its effects has not been evaluated in endemic fish. Goals: Evaluate acute effect of Carbofuran® in juveniles of Chirostoma humboldtianum (Valenciennes, 1835) through neurotoxicity biomarkersf and oxidative stress on brain, liver, gills and muscles. Methods: Effect Carbofuran (0.0, 0.025, 0.05, 0.1, 0.2, 0.4 mg/L) was evaluated in a static essay during 96 h without renewal water on seven-months old juveniles. Fish were obtained by in vitro fertilization, from breeders in captivity, morphologically and genetically certified. Results: CL50 was 0.077 mg/L at 96 h (0.028 – 0.118 mg/L -1, α = 0.05). Acetylcholinesterase activity (AChE) is inhibited in gills and liver. Lipoperoxidation level (LPO) was significantly higher in gills than liver and muscles (p < 0.05). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes present a similar pattern in gills and liver. Conclusions: carbofuran causes neurotoxic and oxidative damage even at lower concentrations than those reported in other fish species.Antecedentes: Las poblaciones de Chirostoma han disminuido por pérdida de su hábitat, la introducción de especies exóticas y la contaminación. Chirostoma humboldtianum (Valenciennes, 1835) se registró en la cuenca de México, por última vez, en 1957. El carbofurán es un insecticida carbámico, sistémico de amplio espectro, por lo que su uso se ha prohibido en muchos países. Sin embargo, en México se utiliza ampliamente y sus efectos no se han evaluado en peces endémicos. Objetivo: Evaluar el efecto agudo del Carbofuran® en juveniles de Chirostoma humboldtianum a través de biomarcadores de neurotoxicidad y de estrés oxidativo en el cerebro, el hígado, las branquias y los músculos. Método: Se evaluó el efecto del carbofuran (0.0, 0.025, 0.05, 0.1, 0.2, 0.4 mg/L, n = 10 y tres réplicas) en un ensayo estático, sin recambio de agua durante 96 h, en juveniles de siete meses de edad. Los peces se obtuvieron por fertilización in vitro, de reproductores mantenidos en cautiverio, certificados morfológica y genéticamente. Resultados: La CL50 fue de 0.077 mg/L-1 (0.028 – 0.118 mg/L -1, α = 0.05) a las 96 h de exposición. La actividad de la acetilcolinesterasa (AchE) se inhibe en el cerebro y en el hígado. El nivel de lipoperoxidación (LPO) fue significativamente mayor en las branquias que en el hígado y los músculos (p < 0.05). Las enzimas superóxido dismutasa (SOD) y glutatión peroxidasa (GPx) presentan un patrón similar de activación en las branquias y el hígado. Conclusiones: El carbofuran causa daño neurotóxico y oxidativo, en juveniles de C. humboldtianum en concentraciones menores a las registradas en otras especies de peces.&nbsp

Physicochemical Characteristics of Transferonƒ Batches

Transferon, a biotherapeutic agent that has been used for the past 2 decades for diseases with an inflammatory component, has been approved by regulatory authorities in Mexico (COFEPRIS) for the treatment of patients with herpes infection. The active pharmaceutical ingredient (API) of Transferon is based on polydispersion of peptides that have been extracted from lysed human leukocytes by a dialysis process and a subsequent ultrafiltration step to select molecules below 10 kDa. To physicochemically characterize the drug product, we developed chromatographic methods and an SDS-PAGE approach to analyze the composition and the overall variability of Transferon. Reversed-phase chromatographic profiles of peptide populations demonstrated batch-tobatch consistency from 10 representative batches that harbored 4 primary peaks with a relative standard deviation (RSD) of less than 7%. Aminogram profiles exhibited 17 proteinogenic amino acids and showed that glycine was the most abundant amino acid, with a relative content of approximately 18%. Further, based on their electrophoretic migration, the peptide populations exhibited a molecular mass of about 10 kDa. Finally, we determined the Transferon fingerprint using a mass spectrometry tool. Because each batch was produced from independent pooled buffy coat samples from healthy donors, supplied by a local blood bank, our results support the consistency of the production of Transferon and reveal its peptide identity with regard to its physicochemical attributes

Pharmacokinetics of acemetacin and its active metabolite indomethacin in rats during acute hepatic damage and liver regeneration

Background and aim:The pharmacokinetics of acemetacin, a non-steroidal anti-inflammatory drug which is biotransformed to indomethacin by hepatic first-pass effect, was examined during the necrotic and regeneration phases resulting from acute hepatitis induced by carbon tetrachloride (CCl4).Material and methods: Acute hepatitis was induced by oral CCl4 administration to male Wistar rats. On days 0, 1 and 3 after the insult, liver histological analysis was performed, biochemical markers of liver damage and regeneration were measured, and the pharmacokinetics of oral acemetacin and of its active metabolite, indomethacin, were determined.Results: One day after CCl4 administration, liver necrosis was apparent and there was an increase in the circulating levels of indicators of liver damage and regeneration with regard to control conditions. Acemetacin bioavailability was increased, although not in a statistically significant manner. On the other hand, indomethacin bioavailability was significantly reduced. By day 3, histological analysis revealed liver recovery, although not complete, while biochemical indicators of hepatic damage had reverted either totally or partially. Markers of liver regeneration were still increased. Bioavailability acemetacin and indomethacin was comparable to control values.In conclusion: Indomethacin bioavailability after oral administration of its precursor, acemetacin, is significantly reduced by acute hepatitis produced by CCl4. Pharmacokinetic alterations, as liver damage, are reversible, but do not require complete liver regeneration to return to basal conditions

Physicochemical Characteristics of Transferon™ Batches

Transferon, a biotherapeutic agent that has been used for the past 2 decades for diseases with an inflammatory component, has been approved by regulatory authorities in Mexico (COFEPRIS) for the treatment of patients with herpes infection. The active pharmaceutical ingredient (API) of Transferon is based on polydispersion of peptides that have been extracted from lysed human leukocytes by a dialysis process and a subsequent ultrafiltration step to select molecules below 10 kDa. To physicochemically characterize the drug product, we developed chromatographic methods and an SDS-PAGE approach to analyze the composition and the overall variability of Transferon. Reversed-phase chromatographic profiles of peptide populations demonstrated batch-to-batch consistency from 10 representative batches that harbored 4 primary peaks with a relative standard deviation (RSD) of less than 7%. Aminogram profiles exhibited 17 proteinogenic amino acids and showed that glycine was the most abundant amino acid, with a relative content of approximately 18%. Further, based on their electrophoretic migration, the peptide populations exhibited a molecular mass of about 10 kDa. Finally, we determined the Transferon fingerprint using a mass spectrometry tool. Because each batch was produced from independent pooled buffy coat samples from healthy donors, supplied by a local blood bank, our results support the consistency of the production of Transferon and reveal its peptide identity with regard to its physicochemical attributes

Favipiravir and/or nitazoxanide: a randomized, double-blind, 2x2 design, placebo-controlled trial of early therapy in COVID-19 in health workers, their household members, and patients treated at IMSS (FANTAZE)

BackgroundThe 2020 pandemic of SARS-CoV-2 causing COVID-19 disease is an unprecedented global emergency. COVID-19 appears to be a disease with an early phase where the virus replicates, coinciding with the first presentation of symptoms, followed by a later 'inflammatory' phase which results in severe disease in some individuals. It is known from other rapidly progressive infections such as sepsis and influenza that early treatment with antimicrobials is associated with a better outcome. The hypothesis is that this holds for COVID-19 and that early antiviral treatment may prevent progression to the later phase of the disease.MethodsTrial design: Phase IIA randomised, double-blind, 2 × 2 design, placebo-controlled, interventional trial.RandomisationParticipants will be randomised 1:1 by stratification, with the following factors: gender, obesity, symptomatic or asymptomatic, current smoking status presence or absence of comorbidity, and if the participant has or has not been vaccinated.BlindingParticipants and investigators will both be blinded to treatment allocation (double-blind).DiscussionWe propose to conduct a proof-of-principle placebo-controlled clinical trial of favipiravir plus or minus nitazoxanide in health workers, their household members and patients treated at the Mexican Social Security Institute (IMSS) facilities. Participants with or without symptomatic COVID-19 or who tested positive will be assigned to receive favipiravir plus nitazoxanide or favipiravir plus nitazoxanide placebo. The primary outcome will be the difference in the amount of virus ('viral load') in the upper respiratory tract after 5 days of therapy. Secondary outcomes will include hospitalization, major morbidity and mortality, pharmacokinetics, and impact of antiviral therapy on viral genetic mutation rate. If favipiravir with nitazoxanide demonstrates important antiviral effects without significant toxicity, there will be a strong case for a larger trial in people at high risk of hospitalization or intensive care admission, for example older patients and/or those with comorbidities and with early disease.Trial registrationClinicalTrials.gov NCT04918927 . Registered on June 9, 2021