Melatonin (MLT) is an endogenous hormone that controls circadian cycle. MLT has additional important properties that make it appealing as a neuroprotective agent—it is a potent anti-oxidant, with anti-apoptotic and anti-inflammatory properties. MLT is safe for administration during pregnancy or to the newborn after birth, and can reduce white matter brain injury under conditions of chronic fetal hypoxia. Accordingly, in the current study, we examined whether an intermediate dose of MLT could restore white matter brain development when administered after an acute hypoxic ischemic (HI) insult in preterm fetal sheep. Fifteen fetal sheep at 95–98 days gestation were instrumented with femoral artery and vein catheters, and a silastic cuff placed around the umbilical cord. At 102 days gestation, the cuff was inflated, causing complete umbilical cord occlusion for 25 min in 10 fetuses, to induce acute severe HI. Five HI fetuses received intravenous MLT for 24 h beginning at 2 h after HI. The remaining five fetuses were administered saline alone. Ten days after HI, the fetal brain was collected from each animal and white and gray matter neuropathology assessed. HI caused a significant increase in apoptotic cell death (TUNEL+), activated microglia (Iba-1+), and oxidative stress (8-OHdG+) within the subventricular and subcortical white matter. HI reduced the total number of oligodendrocytes and CNPase+ myelin density. MLT administration following HI decreased apoptosis, inflammation and oxidative stress within the white matter. MLT had intermediate benefits for the developing white matter: it increased oligodendrocyte cell number within the periventricular white matter only, and improved CNPase+ myelin density within the subcortical but not the striatal white matter. MLT administration following HI was also associated with improved neuronal survival within the cortex. Neuropathology in preterm infants is complex and mediated by multiple mechanisms, including inflammation, oxidative stress and apoptotic pathways. Treatment with MLT presents a safe approach to neuroprotective therapy in preterm infants but appears to have brain region-specific benefits within the white matter.

No abstract

In sepsis, there is an increase in oxidative stress which plays important role in further physiological derangement. Due to its potent antioxidant effect, vitamin C has been proposed as a potential adjunct treatment in patients with sepsis. This study aims to evaluate the benefits of vitamin C administration in patients with sepsis. A systematic search was conducted using electronic databases PubMed, Scopus, ProQuest, and Cochrane with keywords combination of vitamin C/ascorbic acid and sepsis/septic. The limits of the search included English language, human subjects, and adults. To limit the confounding effect, only studies with vitamin C monotherapy were considered for inclusion. Seven relevant studies comprising five clinical trials and two retrospective studies were included in this paper for critical appraisal. Most studies found some clinical benefits with the use of vitamin C in patients with sepsis compared to placebo, such as a reduction in SOFA score and mortality. However, these favourable outcomes were not consistent in all studies. In conclusion, vitamin C is a promising adjunct treatment option in patients with sepsis, however further large, optimized multicenter trials are needed to definitively confirm its benefits. Keywords: vitamin C, ascorbic acid, sepsis, septic shock.   Manfaat Vitamin C Dosis Tinggi untuk Pasien Sepsis Abstrak Kondisi sepsis menyebabkan peningkatan stres oksidatif yang berperan penting dalam menyebabkan gangguan fisiologis lebih lanjut. Karena memiliki efek antioksidan yang kuat, vitamin C telah diusulkan sebagai terapi adjuvan yang menjanjikan pada pasien sepsis. Penelitian ini bertujuan untuk mengevaluasi manfaat pemberian vitamin C pada pasien sepsis. Pencarian sistematis dilakukan menggunakan database elektronik PubMed, Scopus, ProQuest, dan Cochrane dengan kombinasi kata kunci vitamin C/asam askorbat dan sepsis/ septik. Batas pencarian yaitu bahasa Inggris, subjek manusia, dan usia dewasa. Untuk membatasi efek perancu, hanya studi yang menggunakan monoterapi vitamin C yang dipertimbangkan untuk dimasukkan. Tujuh studi relevan yang terdiri dari lima uji klinis dan dua studi retrospektif dimasukkan dalam tulisan ini untuk telaah kritis. Sebagian besar studi mendapatkan manfaat klinis penggunaan vitamin C pada pasien sepsis dibandingkan dengan plasebo, misalnya penurunan skor SOFA dan angka mortalitas, namun hasil positif ini tidak konsisten dalam semua penelitian. Sebagai kesimpulan, vitamin C adalah pilihan terapi adjuvan yang menjanjikan pada pasien sepsis, namun butuh penelitian multisenter yang lebih besar dan optimal untuk memastikan manfaatnya secara definitif. Kata kunci: vitamin C, asam askorbat, sepsis, syok sepsis