Effect of a Structured Teaching Module Including Intensive Prophylactic Measures on Reducing the Incidence of Capecitabine-Induced Hand-Foot Syndrome: Results of a Prospective Randomized Phase III Study

Lessons Learned

• A structured teaching module including intensive prophylactic measures to alleviate hand‐foot syndrome (HFS) during capecitabine therapy is feasible but ineffective at protecting patients from HFS.
• Pharmacologic therapeutic interventions should be investigated for the management of this complication.

BackgroundCapecitabine‐induced hand‐foot syndrome (HFS) has a detrimental effect on quality of life. The effect of a structured teaching module including intensive prophylactic measures was evaluated.MethodsThis non‐crossover phase III double‐blinded clinical trial randomized patients in a 1:1 ratio to either a control group or to a group administered a structured teaching model including intensive prophylactic measures on HFS administered by a trained oncology nurse at regular intervals (case) versus standard information on HFS care administered by treating clinician (control). The primary endpoint was comparison of fraction of patients in both arms developing at least grade 2 HFS.ResultsBetween June 15, 2016, and April 4, 2018, 280 patients (140 to case and 140 to control) were enrolled. The median number of capecitabine chemotherapy cycles was eight; 269 patients (96%) were evaluable for HFS, of whom 89 patients (33.08%) developed at least grade 2 HFS (grade 2 HFS, 73 patients [26.1%]; grade 3 HFS, 16 patients (5.7%}). There was no difference in at least grade 2 HFS between evaluable case and control arms of the study (control group, 45/135 [33.3%]; case, 44/134 [32.8%]; p = .93).ConclusionThe use of a structured teaching module including intensive prophylactic measures was feasible, but this did not reduce the incidence and severity of capecitabine‐induced HFS.     

Therapeutic and fertility restoration effects of Ionidium suffruticosum on sub-fertile male albino Wistar rats: effects on testis and caudal spermatozoa

Context: Ionidium suffruticosum (L.) Ging (Violaceae) is an important medicinal plant widely used as a herbal traditional medicine in Ayurveda for the treatment of infertility. Currently, little pharmacological information is available on its male fertility properties following prolonged use.

Objective: To investigate I. suffruticosum leaf extracts for male fertility parameters.

Materials and methods: The ethanol lyophilized fraction was administered orally on carbendazim-induced sub-fertility rats (250?mg/kg body weight for 28 days). The effects of fractions on rat’s fertility parameters i.e., body and testes weight, sperm motility, sperm vitality, epididymal sperm counts, its morphology, enzyme and antioxidant stress and histopathology were studied and compared with clomiphene citrate.

Results: The sub-fertile male rats treated with I. suffruticosum leaf extract increased the body weight of 7?g, testis weight of 97?mg, increased cauda epididymal sperm counts of 34.2?×?10⁶ sperm/mL, motility of sperm 46% and vitality 28% also increased and normal sperm morphology also improved up to 32%. The carbendazim-treated group showed loss in body weight of 33?g, testis weight of 851?mg, decreased epididymal sperm counts of 15?×?10⁶ sperm/mL, with sluggish motility and a highly significant fall in the live sperms of about 57%.

Discussion and conclusion: The leaf fraction of I. suffructicosum increased the testicular weight, spermatogenesis, sperm counts, lessened sperm agglutination, and increased testicular oxidative biomarkers, SOD, and CAT. This study therefore supports the usage of I. suffructicosum in traditional medicine for infertility.     

Naringenin Decreases α-Synuclein Expression and Neuroinflammation in MPTP-Induced Parkinson’s Disease Model in Mice

The present study was designed to ascertain the role of naringenin (NGN), a citrus fruit flavanone, against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced α-synuclein (SYN) pathology and neuroinflammation in a mouse model. NGN was administered to C57BL/6J mice once a day for 5 consecutive days prior to the MPTP intoxication. On day 5, 40–50 min after the NGN or vehicle administration, MPTP was injected in two divided doses (2× 40 mg/kg, i.p. at 16 h apart). The animals were observed for motor functions 48 h after the first MPTP injection. The animals were then euthanized, the brains collected to analyze SYN pathology, cytokines, and oxidative stress levels in the substantia nigra region. The NGN significantly downregulated SYN and upregulated dopamine transporter (DAT) and tyrosine hydroxylase (TH) protein expressions. It also downregulated tumor necrosis factor-α (TNFα) and interleukin 1β (IL1β) mRNA expressions and improved superoxide dismutase levels. It also reduced glutathione levels when compared to vehicle-treated PD animals. The upregulation of TH corroborates to an increase in dopamine, DOPAC, and homovanillic acid turnover and motor functions with NGN treatment. To summarize, NGN, a dietary flavone, has the potential to counteract MPTP-induced dopaminergic degeneration by regulating SYN pathology, neuroinflammation, and oxidative stress. This warrants the investigation of NGN’s potential effects in a genetic model of PD.