Targeting higher levels of lactate in the post-injury period following traumatic brain injury.

BACKGROUND: Secondary traumatic brain injury (TBI) consequences continue multiple cascades of biochemical reactions caused by initial neurotrauma and one of the important pathogenetic processes is mitochondrial dysfunction partly characterized by elevation of lactate/pyruvate ratio in brain following metabolic failure. OBJECTIVE: To identify lactate, pyruvate, lactate dehydrogenase, tau protein, ceruloplasmin blood levels in the post-injury period following TBI in relation to its different forms. PATIENTS AND METHODS: Ninety-six patients (mean age ± SD 38.8 ± 10.39 years) at 12 months post-injury follow-ups TBI (post-TBI) were investigated; plasma lactate and pyruvate levels were measured by the spectrophotometric method according to the manufacturer protocols; tau protein, ceruloplasmin and lactate dehydrogenase (LDH) were measured in sera by enzyme-linked immunosorbent assays. Group 1 was comprised of 54 participants who had a history of mild TBI, group 2 was comprised of 42 patients who had a history of moderate TBI. RESULTS: In this work, we found the highest plasma lactate levels in the patients with the post-injury period following moderate TBI as compared to controls (p = 0.0047, t = 2.924, 95 % CI -0.2154 to -0.04071) where the median lactate level was 0.832 ± 0.033 and 0704 ± 0.021 mmol/L in controls. No significant differences were seen between mild and moderate post-TBI (p = 0.079; t = 1.772); significant difference was also seen between general post-TBI group versus controls (p = 0.0181; t = 2.396; 95 % CI -0.1627 to -0.01551) with the median total lactate level of 0.793 ± 0.019 mmol/L. Lactate data did not distinguish with the respect to gender or age. The results showed no significant differences in tau protein, pyruvate, LDH and ceruloplasmin levels. CONCLUSION: This study shows higher lactate levels in the post-injury period following TBI that reflect post-injury oxidative dysmetabolism and are more expressed in the post-injury period following moderate TBI.

Targeting Higher Levels of Tau Protein in Ukrainian Patients with Wilson's Disease.

INTRODUCTION: Wilson's disease (WD) is a rare genetic disorder of copper metabolism in which impaired copper homeostasis may enhance amyloid aggregation and trigger neurodegeneration. Tau protein is a highly soluble microtubule-associated phosphoprotein that plays a significant role in microtubule stabilization; it is also a critical component of neurotoxic degenerative mechanisms. Tau has been shown to be involved in neuronal degeneration and axonal damage, and impaired copper metabolism has been shown to be involved in copper intoxication and thus associated with the processes of neurodegeneration and cellular damage. We have therefore investigated tau protein as a potential marker of axonal impairment and neurodegeneration. METHODS: Patients with WD (n = 47; mean age ± standard deviation [SD] 30.19 ± 7.87 years; mean disease duration : 10.06 ± 3.9 years) and healthy controls (HC; n = 30; mean age 29.6 ± 4.73 years) were tested for serum tau protein levels using an enzyme-linked immunosorbent assay method. All patients were receiving a stable penicillamine dose as ongoing therapy. RESULTS: Patients with WD had a higher mean tau protein level than did the HC (221.7 ± 135.1 vs. 71.14 ± 20.56 pg/mL, p < 0.0001). Patients with WD also had abnormally high serum tau protein levels (t statistic 6.047, 95% confidence interval - 218.2 to - 95.86) in both the cerebral and hepatocerebral forms of WD, with patients having the cerebral form showing a tendency toward higher tau levels. We found that tau protein did not differ according to gender, disease duration, age at disease onset, ceruloplasmin serum level and copper serum level. CONCLUSION: This study provides novel data revealing that high tau protein levels in WD patients could be a potential biomarker for axonal impairment and possible neuronal damage due to tau protein, leading to neurodegeneration in WD.

Rhodiola rosea in Subjects with Prolonged or Chronic Fatigue Symptoms: Results of an Open-Label Clinical Trial.

BACKGROUND: Rhodiola rosea roots and rhizomes are a herbal medicine for temporary relief of stress symptoms such as fatigue and sensed weakness. A daily dosage of 400 mg is recommended. METHODS: A dry ethanolic extract of R. rosea (WS® 1375) was studied in 100 subjects with prolonged or chronic fatigue symptoms. In an uncontrolled, open-label multicenter clinical trial, the subjects were administered 2 × 200 mg WS® 1375 over 8 weeks. Outcome measures were scales and tests related to fatigue. They were evaluated in an exploratory data analysis to generate hypotheses regarding efficacy. The pilot character of the trial is marked by its broad focus on subjects suffering from fatigue in general and by its comparatively long duration. RESULTS: The greatest change was observed after 1 week of treatment. The fatigue symptoms continued to decline further, with statistically significant improvement at week 8. The safety assessments of WS® 1375 during the trial proved to be favorable, with most adverse events being of mild intensity and not related to the study drug. CONCLUSIONS: The results indicate that 2 × 200 mg WS® 1375 may be an effective treatment in subjects suffering from prolonged or chronic fatigue. The safety and tolerability of WS® 1375 also presented a favorable profile.