Abordaje multidisciplinarde un paciente con una úlceraperianal asociada a pomadaantihemorroidal / Multidisciplinary approach to a patient with a perianal ulcer associated with hemorrhoidal ointment

Introducción: Hasta la fecha, la manifestación de una úlcera perianalprovocada por una pomada antihemorroidal no se ha descrito confrecuencia. Sin embargo, se ha objetivado un incremento de loscasos durante la pandemia de COVID-19. Caso clínico: Varónde 82 años independiente, que presentó una úlcera perianal de35,8 cm² sin ninguna patología ni enfermedad concomitante queexplicara su causa. La aplicación de criterios de exclusión exhaustivos,incluida una biopsia para rechazar el pioderma gangrenoso,identificó una pomada rectal hemorroidal como la causa de la úlcera.Plan de actuación: La herida curó tras aplicar una intervenciónmultidisciplinaria y una terapia con factores de crecimientoautólogos. Discusión y conclusiones: Este caso ha sido escasamentereportado en la literatura, aunque esta pomada hemorroidal secomercializa desde hace más de 40 años. Se recomienda evaluaciónmédica antes de la prescripción. (AU)

Introduction: Perianal ulcers resulting from the use of hemorrhoidalointments have been rarely reported to date. Nevertheless, therehas been a surge in the number of cases reported during theCOVID-19 pandemic. Case report: An independent 82-year-oldmale experienced a 35,80 cm² perianal ulcer, with no underlyingcondition or concomitant disease that could explain the cause ofthe ulcer. The application of thorough exclusion criteria, including abiopsy to rule out pyoderma gangrenosum, led to the identificationof a hemorrhoidal rectal ointment as the cause. Action plan: Theulcer healed completely when a multidisciplinary intervention and anautologous growth factors advanced therapy were applied. Discussionand conclusions: This case has been scarcely reported in the literature,although this hemorrhoidal ointment has been on the market for over40 years. Medical assessment before prescription and patients’ followup is recommended. (AU)

Inhibitory effects of sodium pentosan polysulfate on formation and function of osteoclasts derived from canine bone marrow.

BACKGROUND: Sodium pentosan polysulfate (NaPPS) was testified as a chondroprotective drug in with a detailed rationale of the disease-modifying activity. This study was undertaken to determine whether anti-osteoarthritis drug, NaPPS inhibited osteoclasts (OC) differentiation and function. Canine bone marrow mononuclear cells (n = 6) were differentiated to OC by maintaining with receptor activator of nuclear factor kappa B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for up to 7 days with the treatment of NaPPS at concentration of 0, 0.2, 1 and 5 µg/mL. Differentiation and function of OC were accessed using tartrate-resistant acid phosphate (TRAP) staining and bone resorption assay, while monitoring actin ring formation. Invasion and colocalization patterns of fluorescence-labeled NaPPS with transcribed gene in OC were monitored. Gene expression of OC for cathepsin K (CTK), matrix metallopeptidase-9 (MMP-9), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos, activator protein-1(AP-1) and carbonic anhydrase II was examined using real-time PCR. RESULTS: Significant inhibition of OC differentiation was evident at NaPPS concentration of 1 and 5 µg/mL (p < 0.05). In the presence of 0.2 to 5 µg/mL NaPPS, bone resorption was attenuated (p < 0.05), while 1 and 5 µg/mL NaPPS achieved significant reduction of actin ring formation. Intriguingly, fluorescence-labeled NaPPS invaded in to cytoplasm and nucleus while colocalizing with actively transcribed gene. Gene expression of CTK, MMP-9 and NFATc1 were significantly inhibited at 1 and 5 µg/mL (p < 0.05) of NaPPS whereas inhibition of c-Fos and AP-1 was identified only at concentration of 5 µg/mL (p < 0.05). CONCLUSIONS: Taken together, all the results suggest that NaPPS is a novel inhibitor of RANKL and M-CSF-induced CTK, MMP-9, NFATc1, c-Fos, AP-1 upregulation, OC differentiation and bone resorption which might be a beneficial for treatment of inflammatory joint diseases and other bone diseases associated with excessive bone resorption.

Immunomodulatory activity of orphan drug Elmiron® in female B6C3F1/N mice.

Interstitial cystitis (IC) is a chronic disorder characterized by bladder discomfort and urinary urgency in the absence of identifiable infection. Despite the expanding use in IC treatment and other chronic conditions, the effects of Elmiron® treatment on immune system remain unknown. Therefore, female B6C3F1/N mice were orally administered Elmiron® daily for 28-days at doses of 63, 125, 250, 500 or 1000mg/kg to evaluate its immunomodulatory effects. Mice treated with Elmiron® had a significant increase in absolute numbers of splenic macrophages (63, 500 and 1000mg/kg) and natural killer (NK) cells (250 and 1000mg/kg). Elmiron® treatment did not affect the humoral immune response or T cell proliferative response. However, innate immune responses such as phagocytosis by liver macrophages (1000mg/kg) and NK cell activity were enhanced (500 and 1000mg/kg). Further analysis using a disease resistance model showed that Elmiron®-treated mice demonstrated significantly increased anti-tumor activity against B16F10 melanoma cells at the 500 and 1000mg/kg doses. Collectively, we conclude that Elmiron® administration stimulates the immune system, increasing numbers of specific cell populations and enhancing macrophage phagocytosis and NK cell activity in female B6C3F1/N mice. This augmentation may have largely contributed to the reduced number of B16F10 melanoma tumors.