No abstract

Painful peripheral neuropathy is the main dose-limiting and long lasting side-effect of paclitaxel therapy. Despite enormous research, there is no effective treatment for paclitaxel-induced peripheral neuropathic pain owing to poor understanding of pathophysiological mechanisms. Growing evidence indicates oxidative-nitrosative stress is one of the leading factors causing chemotherapy induced peripheral neuropathy. Recently, involvement of neuroinflammation has been suggested in the development of paclitaxel-induced neuropathic pain. It is postulated that abrogating cytokine release and improving antioxidant defenses might be suitable targets in controlling neuroinflammation and oxidative-nitrosative stress mediated nociceptive hypersensitivities. Therefore, the study evaluated the effect of curcumin on paclitaxel-induced neuropathic pain in rats. Peripheral neuropathy was induced by administration of paclitaxel (2 mg/kg per injection) intraperitoneally on four alternate days (days 0, 2, 4, 6). Thermal hyperalgesia and mechanical allodynia were assessed and the markers of inflammation and oxidative-nitrosative stress were estimated. Administration of curcumin (50 and 100 mg/kg, p.o.) for 2 weeks started 14 days after paclitaxel injection significantly alleviated paclitaxel-induced nociceptive behavioural hypersensitivity observed as reduced thermal hyperalgesia and mechanical allodynia. These observed ameliorative effects of curcumin on paclitaxel-induced neuropathic pain are accompanied by reduction of tumour necrosis factor-α, a pro-inflammatory cytokine, in both spinal cord and dorsal root ganglia and oxidative-nitrosative stress in spinal cord. The results of the present study demonstrated antihyperalgesic and antiallodynic effects of curcumin. Additional clinical studies are warranted to evaluate therapeutic potential of curcumin as antinociceptive agent in the treatment of paclitaxel-induced neuropathic pain.

Chronic kidney disease (CKD) patients are prone to infections and inevitably require antibiotics. Antimicrobial resistance (AMR) is a global threat to humans. Indeed, the most important cause for spread of AMR is irrational use of antibiotics. Therefore, the present study evaluates prescribing practice of antibiotics in CKD patients. A cross-sectional study was carried out in 382 CKD in-patients prescribed with antibiotics. The data were analysed using the WHO prescribing indicators and the WHO Access, Watch, and Reserve (AWaRe) classification. The average number of drugs prescribed per encounter was 3.1. Antibiotics prescribed by generic name and prescribed from the Essential Medicines List were 52.9% and 47.1%, respectively. % Encounters with antibiotics and parenteral antibiotics were 59.2% and 77.4%, respectively. Third generation cephalosporins (76.9%), particularly cefoperazone (40%) and ceftriaxone (21.2%), were the most commonly prescribed antibiotics. A total of 19 specific antibiotics (Access 5, Watch 13, Reserve 1, and Not Recommended 0) were prescribed. According to WHO AWaRe classification, 10.6%, 89%, and 0.4% of antibiotics prescribed were from the ‘Access’, ‘Watch’, ‘Reserve’ categories, respectively. ‘Watch’ category antibiotics, particularly cephalosporins (98%), were prescribed in high rate. The most commonly prescribed ‘Access’ and ‘Watch’ category antibiotics were amikacin (37%) and cefoperazone (44.9%), respectively. Amoxicillin index was 1.6 and ‘Access-to-Watch’ index was 0.1, which were below the priority values. Prescription pattern of antibiotics observed in this study was not fully met the WHO recommendations. Additionally, ‘Watch’ category antibiotics, particularly cephalosporins, were prescribed frequently. Changes in prescription pattern and monitoring of antibiotic use are essential to preserve effectiveness and promote rational use of antibiotics, and to overcome AMR.