Integrative Inducer Intervention and Transcriptomic Analyses Reveal the Metabolism of Paralytic Shellfish Toxins in Azumapecten farreri.

Paralytic shellfish toxins (PSTs) are widely distributed neurotoxins, and the PST metabolic detoxification mechanism in bivalves has received increasing attention. To reveal the effect of phase I (cytochrome P450)-II (GST)-III (ABC transport) metabolic systems on the PST metabolism in Azumapecten farreri, this study amplified stress on the target systems using rifampicin, dl-α-tocopherol, and colchicine; measured PST levels; and conducted transcriptomic analyses. The highest toxin content reached 1623.48 µg STX eq/kg in the hepatopancreas and only 8.8% of that in the gills. Inducer intervention significantly decreased hepatopancreatic PST accumulation. The proportional reductions in the rifampicin-, dl-α-tocopherol-, and colchicine-induced groups were 55.3%, 50.4%, and 36.1%, respectively. Transcriptome analysis showed that 11 modules were significantly correlated with PST metabolism (six positive/five negative), with phase I CYP450 and phase II glutathione metabolism significantly enriched in negatively correlated pathways. Twenty-three phase I-II-III core genes were further validated using qRT-PCR and correlated with PST metabolism, revealing that CYP46A1, CYP4F6, GSTM1, and ABCF2 were significantly correlated, while CYP4F11 and ABCB1 were indirectly correlated. In conclusion, phase I-II-III detoxification enzyme systems jointly participate in the metabolic detoxification of PSTs in A. farreri. This study provides key data support to profoundly elucidate the PST metabolic detoxification mechanism in bivalves.

Changes of Mycobacterium tuberculosis specific antigen-stimulated CD27-CD38+IFN-γ+CD4+ T cells before and after anti-tuberculosis treatment.

BACKGROUND: The aim of the study was to investigate whether the expression of CD27-CD38+ in interferon (IFN)-γ+CD4+ T cells stimulated by the specific antigen early secreted antigenic target-6 (ESAT-6)/culture filter protein-10 (CFP-10) could be a potential new therapeutic evaluation indicator for anti-tuberculosis (TB) treatment. METHODS: Newly diagnosed active pulmonary TB patients, latent TB infection (LTBI) and healthy controls were enrolled from January 2021 to December 2021. PTB patients were treated by standard anti-TB regimen 2HREZ/4HR (2 months of isoniazid (H), rifampin (R), ethambutol (E), and pyrazinamide (Z) followed by 4 months of isoniazid (H) and rifampin (R)). The difference of CD27-CD38+ expression in IFN-γ+CD4+ T cells before treatment, 2 months after treatment, and 6 months after treatment were compared. RESULTS: Total 45 PTB patients, 38 LTBI cases and 43 healthy controls were enrolled. The expression of CD27-CD38+ decreased significantly after anti-TB treatment and was comparable with that in LTBI and healthy controls when the 6-month anti-TB treatment course was completed. The decline rate of CD27-CD38+ between 6 months after treatment and baseline was positively correlated with erythrocyte sedimentation rate (r = 0.766, P < 0.0001), C-reactive protein (r = 0.560, P = 0.003) and chest computerized tomography severity score (r = 0.632, P = 0.0005). The area under receiver operator characteristic curve of CD27-CD38+ in distinguish pulmonary TB patients before and after treatment was 0.779. CONCLUSION: The expression of CD27-CD38+ in ESAT-6/CFP-10 stimulated IFN-γ+CD4+T cells can well reflect the changes of the disease before and after anti-TB treatment, which is expected to be a potential new therapeutic evaluation index. Clinical Registry number chiCTR1800019966.

Úlcera de Buruli. Una enferfermad "menos" olvidada / No disponible

No disponible

Escrofuloderma / Scrofuloderma

Presentamos una paciente que consultó en su centro de salud por una masa en región supraclavicular derecha. Tras su valoración clínica y con sospecha diagnóstica de escrofuloderma, se realizaron las exploraciones pertinentes para confirmar el diagnóstico e indicar el tratamiento específico(AU)

We presented a patient who sought medical attention at a health centre concerning a mass in the right supraclavicular area. After clinical evaluation and with diagnostic suspicion of scrofuloderma, appropriate examinations were carried out to confirm the diagnosis and to advise specific treatment(AU)

Excreción de fármacos. El proceso farmacocinético: ¿Llega el fármaco al sitio de acción? / Pharmacokinetic process: does the site of drug action? Excretion of drugs

El riñón constituye la vía principal de excreción de fármacos fuera del organismo. Junto con el aparato urinario, los fármacos se excretan a través de otras vías como los pulmones, la leche materna, el sudor, la secreción lagrimal y genital (la rifampicina produce una coloración rojo anaranjada), la bilis y la saliva. La excreción de algunos compuestos por via biliar (p.ej. cloranfenicol), puede dar lugar a un fenómeno de recirculación entero-hepática como consecuencia de la reactivación mediante hidrólisis intestinal de los metabolitos y su posterior reabsorción. Además de cloranfenicol, otros fármacos excretados a través de la bilis son la morfina, la rifampicina, las tetraciclinas y la digoxina. La saliva puede ser útil para la monitorización de fármacos que se concentran especialmente en este medio. Tres procesos determinan la excreción renal: la filtración glomerular, la reabsorción tubular pasiva y la secreción tubular activa. La excreción total de un fármaco en la orina es la resultante de dichos procesos, de forma que excreción renal= filtración + secreción – reabsorción. Si un compuesto farmacológico es inactivado, principalmente a través del metabolismo, la función renal no es un factor relevante en su eliminación. Sin embargo, la alteración de la función renal (p.ej. en la insuficiencia renal crónica) constituye un factor relevante en la eliminación de fármacos cuando éstos, o sus metabolitos activos, se expulsan principalmente por el riñón, sin transformación metabólica previa. En esta situación es recomendable ajustar la dosis en el paciente(AU)

The main route of excretion of drugs is the kidney. Other routes include the lungs; breast milk; sweat; tears, and genital secretions (alarming if the patient is not expecting the orange-red discoloration caused by rifampicin); bile (leading to recirculation of some compounds, for example chloramphenicol, whose inactive metabolites are reactivated by hydrolysis in the gut, morphine, rifampicin, tetracyclines, and digoxin); and saliva (sometimes used in monitoring drug concentrations in body fluids). Three processes determine the renal excretion of drugs: glomerular filtration, passive tubular reabsorption and active tubular secretion. Thus, total renal excretion= excretion by filtration + excretion by secretion – retention by reabsorption. If an active drug is metabolized mainly to inactive compounds, renal function will not greatly affect elimination of the parent compound. However, if the drug or an active metabolite is excreted unchanged via the kidneys, changes in renal function (i.e. chronic renal failure) will influence its elimination. Therefore, dose adjustment of the drug should be recommended(AU)