Albumin supplementation may have limited effects on prolonged hypoalbuminemia in major burn patients: An outcome and prognostic factor analysis.

BACKGROUND: Burns that affect ≥20% of the total body surface area (TBSA) trigger a major inflammatory response in addition to capillary leakage and loss of serum proteins including albumin. Persistent hypoalbuminemia is therefore common in major burn patients. The purpose of this study was to determine whether human albumin solutions can benefit major burn patients with persistent hypoalbuminemia. METHODS: We conducted a retrospective review of major burn patients with ≥20% of TBSA involved at Taipei Veterans General Hospital between January 2007 and December 2018. Thirty-eight patients were enrolled. Patient demographics, burn characteristics, fluid balance, laboratory results, and outcomes were recorded through chart review. RESULT: No significant differences were found in the baseline characteristics of patients who received <25 mg/kg/%TBSA/day of human albumin solutions and those who received more than this amount. Renal replacement therapy, duration of mechanical ventilation, length of stay in the burn unit, and in-hospital mortality rate were not statistically different between the two groups. The serum C-reactive protein/albumin ratio was associated with in-hospital mortality (p = 0.036). CONCLUSION: The administration of large amounts of albumin supplements for the correction of prolonged hypoalbuminemia in major burn patients had no significant benefits on mortality.

Melatonin successfully rescues hippocampal bioenergetics and improves cognitive function following drug intoxication by promoting Nrf2-ARE signaling activity.

Prolonged exposure to gamma-hydroxybutyric acid (GHB) would cause drug intoxication in which impaired cognitive function results from enhanced hippocampal oxidative stress may serve as a major symptom in this deficiency. Considering melatonin possesses significant anti-oxidative efficacy, this study aimed to determine whether melatonin would successfully promote the nuclear factor erythroid 2-related factor 2 and antioxidant responsive element (Nrf2-ARE) signaling, depress oxidative stress, and rescue hippocampal bioenergetics and cognitive function following drug intoxication injury. Adolescent rats subjected to 10 days of GHB were received melatonin at doses of either 10 or 100 mg/kg. Time-of-flight secondary ion mass spectrometry, biochemical assay, quantitative histochemistry, [14 C]-2-deoxyglucose analysis, together with Morris water maze were employed to detect the molecular signaling, oxidative status, bioenergetic level, as well as the cognitive performances, respectively. Results indicated that in GHB-intoxicated rats, enhanced oxidative stress, increased cholesterol level, and decreased anti-oxidative enzymes activities were detected in hippocampal regions. Intense oxidative stress paralleled well with reduced bioenergetics and poor performance in behavioral testing. However, in rats treated with melatonin following GHB intoxication, all above parameters and cognitive function were gradually returned to nearly normal levels. Melatonin also remarkably promoted the translocation of Nrf2 from cytoplasm to nucleus in a dose-dependent manner, thereby increased the Nrf2-ARE signaling-related downstream anti-oxidative enzymes activities. As melatonin effectively rescues hippocampal bioenergetics through depressing the oxidative stress by promoting Nrf2-ARE molecular machinery, this study thus highlights for the first time that clinical use of melatonin may serve as a therapeutic strategy to improve the cognitive function in unsuspecting victims suffered from GHB intoxication injury.

Early-life sleep deprivation persistently depresses melatonin production and bio-energetics of the pineal gland: potential implications for the development of metabolic deficiency.

Early-life sleep deprivation (ESD) is a serious condition with severe metabolic sequelae. The pineal hormone melatonin plays an important role in homeostatic regulation of metabolic function. Considering norepinephrine-mediated Ca(2+) influx and subsequent protein kinase A (PKA) activation is responsible for downstream cAMP-response element-binding protein (CREB) phosphorylation and melatonin biosynthesis, the present study determined whether Ca(2+) expression, together with the molecular machinery participated in melatonin production would significantly alter after ESD. Weaning rats subjected to chronic ESD and maintained naturally (light:dark cycle = 12:12) to adulthood were processed for time-of-flight secondary ion mass spectrometry, immunoblotting, immunohistochemistry together with spectrometric assay to detect the Ca(2+) signaling, adrenoreceptors, PKA, phosphorylated CREB (pCREB) as well as the serum level of melatonin, respectively. Pineal bio-energetics and metabolic function were determined by measuring the cytochrome oxidase activity and serum level of glucose, triglyceride, insulin, high- and low-density lipoproteins, respectively. Results indicated that in normal rats, strong Ca(2+) signaling along with intense adrenoreceptors, PKA, and pCREB activities were all detected in pinealocytes. Enhanced Ca(2+) imaging and signaling pathway corresponded well with intact bio-energetics, normal melatonin production and metabolic activity. However, following ESD, not only Ca(2+) but also pineal signaling activities were all significantly decreased. Blood analysis showed reduced melatonin level and impaired metabolic function after ESD. As depressed Ca(2+)-mediated signaling pathway and melatonin biosynthesis are positively correlated with the development of metabolic dysfunction, supplementary use of melatonin in childhood may thus serve as a practical way to prevent or counteract the ESD-induced metabolic deficiency.