Novel Mechanism for an Old Drug: Phenazopyridine is a Kinase Inhibitor Affecting Autophagy and Cellular Differentiation

Phenazopyridine is a widely used drug against urinary tract pain. The compound has also been shown to enhance neural differentiation of pluripotent stem cells. However, its mechanism of action is not understood. Based on its chemical structure, we hypothesized that phenazopyridine could be a kinase inhibitor. Phenazopyridine was investigated in the following experimental systems: 1) activity of kinases in pluripotent stem cells; 2) binding to recombinant kinases, and 3) functional impact on pluripotent stem cells. Upon addition to pluripotent stem cells, phenazopyridine induced changes in kinase activities, particularly involving Mitogen-Activated Protein Kinases, Cyclin-Dependent Kinases, and AKT pathway kinases. To identify the primary targets of phenazopyridine, we screened its interactions with 401 human kinases. Dose-inhibition curves showed that three of these kinases interacted with phenazopyridine with sub-micromolar binding affinities: cyclin-G-associated kinase, and the two phosphatidylinositol kinases PI4KB and PIP4K2C, the latter being known for participating in pain induction. Docking revealed that phenazopyridine forms strong H-bonds with the hinge region of the ATP-binding pocket of these kinases. As previous studies suggested increased autophagy upon inhibition of the phosphatidyl-inositol/AKT pathway, we also investigated the impact of phenazopyridine on this pathway and found an upregulation. In conclusion, our study demonstrates for the first time that phenazopyridine is a kinase inhibitor, impacting notably phosphatidylinositol kinases involved in nociception.

A comparison of the acute toxicities using moderate hypo-fractionated intensity-modulated radiation therapy or volumetric modulated arc therapy for the treatment of early-stage prostate cancer

AimThis study compared the acute toxicities reported during radiotherapy treatment using either intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) to deliver a moderate hypo-fractionated treatment for early-stage prostate cancer.Material and methodsAcute toxicities are routinely reported at the clinical site for all patients using the Common Terminology Criteria for Adverse Events. Toxicity assessment is performed on day 1 of treatment, then once weekly thereafter. The recorded toxicities of 40 cases treated with five-field IMRT, and 32 cases treated using VMAT were retrospectively compared. All cases were prescribed 73·68 Gy in 28 fractions. Eight symptoms were assessed; diarrhoea, proctitis, fatigue, pain, dermatitis, urinary frequency, urinary retention and urinary tract pain.ResultsIn terms of the overall toxicity recorded, VMAT was shown to reduce the toxicities of dermatitis, fatigue, pain and urinary frequency (p<0·05). Using IMRT, grade 2 toxicities were reported for proctitis, pain, urinary frequency, urinary retention and urinary tract pain. Using VMAT, grade 2 toxicities were reported for urinary frequency and urinary retention.FindingsThe research reported here is one of the first publications to demonstrate that VMAT is associated with decreased toxicities compared with IMRT for the treatment of early-stage prostate cancer.

UJI EFEK EKSTRAK DAUN LIDAH BUAYA (Aloe vera L.) TERHADAP PENYEMBUHAN LUKA INSISI KULIT KELINCI (Oryctolagus cuniculus)

Aloe vera has been used for thousands years to treat burns, hair loss, skin infections, sinus inflamation and gastro-intestinal tract pain. Previous researches showed that Aloe vera works effectively as anti-inflammatory, anti-pyretic, anti-fungal, anti-oxidant, anti-septic, anti-microbial, and anti-viral. This study aimed to evaluate the effect of aloe vera extract on wound healing in incised rabbit skin. This was an experimental study using 3 rabbits as test animals. The rabbits right and left backs were incised for 4 cm long and 2 mm deep. The wound on the right back was given aloe leaf extract , and the wound on the left back was not. The length of the wounds were measured everyday for 2 weeks. ResThe results showed that the wounds that were given aloe leaf extract dried and healed faster. Conclusion: Aloe vera extract accelerated wound healing in the incised rabbit skin.Keywords: aloe vera leaf extract, incision woundAbstrak: Lidah buaya digunakan sebagai bahan obat sejak beberapa ribu tahun yang lalu untuk mengobati luka bakar, rambut rontok, infeksi kulit, peradangan sinus, dan rasa nyeri pada saluran cerna. Beberapa peneliti terdahulu telah membuktikan bahwa Aloe vera berkhasiat sebagai antiinflamasi, antipiretik, antijamur, antioksidan, antiseptik, antimikroba, serta antivirus. Penelitian ini bertujuan untuk mengetahui efek pemberian ekstraksi lidah buaya terhadap penyembuhan luka insisi kulit kelinci. Penelitian ini mengunakan metode eksperimental, dengan menggunakan 3 ekor kelinci sebagai hewan uji. Punggung kanan dan kiri kelinci diinsisi sepanjang 4 cm dan kedalaman 2 mm. Luka pada punggung kanan diberi ekstrak daun lidah buaya sedangkan luka pada punggung kiri tidak diberi ekstrak daun lidah buaya. Pemberian ekstrak daun lidah buaya dan pengukuran panjang luka dilakukan setiap hari selama 2 minggu. Hasil penelitian memperlihatkan luka insisi kulit kelinci yang diberi ekstrak daun lidah buaya lebih cepat kering dan sembuh dibandingkan dengan luka insisi kulit kelinci yang tidak diberikan ekstrak daun lidah buaya. Simpulan: Pemberian ektrak daun lidah buaya memiliki efek untuk mempercepat penyembuhan luka insisi pada kulit kelinci.Kata kunci: ekstrak daun lidah buaya, luka insisi