RESUMO
The use of azathioprine (AZA) in human medicine dates back to research conducted in 1975 that led to the development of several drugs, including 6-mercaptopurine. In 1958, it was shown that 6-mercaptopurine decreased the production of antibodies against earlier administered antigens, raising the hypothesis of an immunomodulatory effect. AZA is a prodrug that belongs to the thiopurine group of drugs that behave as purine analogs. After absorption, it is converted into 6-mercaptopurine. Subsequently, it can be degraded through various enzymatic pathways into inactive compounds and biologically active compounds related to the mechanism of action, which has been the subject of study to evaluate a possible antiviral effect. This study aims to examine the metabolism, mechanism of action, and antiviral potential of AZA and its derivatives, exploring AZA impact on antiviral targets and adverse effects through a narrative literature review. Ultimately, the review will provide insights into the antiviral mechanism, present evidence of its in vitro effectiveness against various DNA and RNA viruses, and suggest in vivo studies to further demonstrate its antiviral effects.
RESUMO
The bean (Phaseolus vulgaris) pathogen Pseudomonas syringae pv. phaseolicola NPS3121 synthesizes phaseolotoxin in a thermoregulated way, with optimum production at 18 °C. Gene PSPPH_4550 was previously shown to be thermoregulated and required for phaseolotoxin biosynthesis. Here, we established that PSPPH_4550 is part of a cluster of 16 genes, the Pbo cluster, included in a genomic island with a limited distribution in P. syringae and unrelated to the possession of the phaseolotoxin biosynthesis cluster. We identified typical non-ribosomal peptide synthetase, and polyketide synthetase domains in several of the pbo deduced products. RT-PCR and the analysis of polar mutants showed that the Pbo cluster is organized in four transcriptional units, including one monocistronic and three polycistronic. Operons pboA and pboO are both essential for phaseolotoxin biosynthesis, while pboK and pboJ only influence the amount of toxin produced. The three polycistronic units were transcribed at high levels at 18 °C but not at 28 °C, whereas gene pboJ was constitutively expressed. Together, our data suggest that the Pbo cluster synthesizes secondary metabolite(s), which could participate in the regulation of phaseolotoxin biosynthesis.
Assuntos
Família Multigênica/genética , Ornitina/análogos & derivados , Pseudomonas syringae/genética , Regulação da Temperatura Corporal , Ornitina/biossíntese , Pseudomonas syringae/metabolismoRESUMO
El tratamiento del glaucoma se realiza con el objetivo de disminuir los niveles de presión intraocular, único factor tratable hasta el momento, y debe ser individualizado. Se presenta un paciente masculino de 54 años de edad, de piel mestiza, intelectual, con antecedentes de aparente salud y diagnóstico de glaucoma desde hace 10 años. Se realizó trabeculectomía con antimetabolito (mitomicina C) en el ojo izquierdo en el año 2012 por daño glaucomatoso avanzado. En el año 2016 acudió a nuestra consulta y refirió mala visión y descontrol de la presión intraocular de ambos ojos. Se constataron cifras muy elevadas de presión intraocular en ambos ojos, superiores a 30 mmHg; en el ojo derecho la unidad de visión con su mejor corrección y un daño campimétrico muy avanzado limitado a una isla de visión central con caída hasta los 5° centrales, y el ojo izquierdo no alcanzaba la percepción luminosa. Después de combinar 3 líneas farmacológicas con la dosis máxima, los valores de la presión intraocular no eran protectores. Surgió la disyuntiva entre realizar una cirugía filtrante, temiendo al riesgo quirúrgico elevado y tratándose de un ojo único, o no practicar cirugía alguna y solo continuar con el tratamiento farmacológico a pesar de no conseguirse valores de presión intraocular meta. Se decidió realizar esclerectomía profunda no penetrante con antimetabolito (mitomicina C al 0,02 por ciento). No se presentaron complicaciones asociadas y se consiguió el descenso de la presión intraocular a 24 mmHg, por lo que al mes de la cirugía se realizó goniopuntura. Se obtuvo la presión intraocular objetivo, sin progresión del daño glaucomatoso y hubo conservación de la agudeza visual(AU)
Treatment for glaucoma is aimed at reducing the levels of intraocular pressure. This is the only factor that may be treated so far, and it should be individualized. A case is presented of a male 54-year-old mulatto patient, intellectual, with a history of apparently good health who was diagnosed with glaucoma ten years ago. Trabeculectomy with antimetabolite (mitomycin C) was performed on the patient's left eye in the year 2012 due to advanced glaucomatous damage. In the year 2016 the patient attended our service and reported poor vision and uncontrolled intraocular pressure in both eyes. Very high intraocular pressure values above 30 mmHg were confirmed in both eyes. In the right eye the vision unit with its best correction, and very advanced campimetric damage limited to a central vision island with a fall to 5° central, whereas the left eye did not achieve light perception. After combining 3 drug lines at their maximum dosage, intraocular pressure values were not protective. The dilemma arose whether to perform filtration surgery, fearing the high surgical risk, being as it was a single eye, or not to perform any surgery and just go on with the drug treatment despite not having achieved target intraocular pressure values. It was decided to perform non-penetrating deep sclerectomy with antimetabolite (0.02 percent mitomycin C). No associated complications occurred and intraocular pressured fell to 24 mmHg. Therefore, goniopuncture was performed one month after surgery. The target intraocular pressure was obtained without glaucomatous damage progression and visual acuity was preserved(AU)
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Trabeculectomia/métodos , Mitomicina/uso terapêutico , Pressão Intraocular/efeitos dos fármacos , Glaucoma/diagnóstico , Glaucoma/terapiaRESUMO
A estabilidade físico-química de soluções injetáveis de folinato de cálcio (leucovorina cálcica), fluoruracila e metotrexato (Fauldleuco, Fauldfluor e Fauldmetro, respectivamente) mantidas nas suas embalagens primárias foram avaliadas após perfuração quanto ao aspecto das soluções, pH, identificação do fármaco, dosagem, material particulado e substâncias relacionadas. Os resultados demonstraram não haver alterações físico-químicas significativas após perfuração da embalagem primária quando armazenada à temperatura ambiente (20 a 25ºC) por 7 dias para as soluções injetáveis de fluoruracila e metotrexato e quando mantidas em geladeira (2 a 8ºC) por 7 dias para as soluções injetáveis de folinato de cálcio. Em todas as avaliações as amostras ficaram protegidas da luz...