Prognostic factors of neuroinflammation and oxidative stress in brain injury patients at Cipto Mangunkusumo Hospital Jakarta.

Background: This study aims to determine the association between neuroinflammation and oxidative stress with prognosis of brain injury patients and the association between neurosurgical procedure with neuroinflammation and oxidative stress condititons. Methods: The study design is a prospective observation of 40 brain injury patients who underwent surgery. IL-6, uric acid, MDA, NR2A antibodies and GSH serum level of pre- and 1 day post-operation on brain injury patients were measured, and their association with GCS, GOS and neurosurgical procedures were analyzed. Results: The post-operative IL-6 serum level showed a downward trend compared to pre-operative value (mean decrease: -190.61 pg/mL). The post-operative IL-6 level was significantly associated with GCS 7 days post-operation (p = 0.006), with OR 24. The post-operative IL-6 serum level was significantly associated with GOS 3 months post-trauma (p = 0.016) with OR 11.6. The post-operative uric acid serum level showed a downward trend compared to pre-operative value (mean decrease: -0.26 mg/dL). There was a significant difference between the mean value of post-operative uric acid serum level in patients with 7 days post-trauma with GCS ≤ 8 (mean: 4.16 mg/dL) and GCS > 8 (mean: 2.71 mg/dL), (p = 0.042). The post-operative MDA serum level showed a downward trend compared to pre-operative value (mean decrease: -0.08 nmol/mL). There is no significant association between MDA serum level, GCS and GOS and no significant association of NR2A antibody and GSH serum level with GCS, GOS and neurosurgical procedure. From the multivariate analysis, the most important neuroinflammatory variable associated with GCS and GOS is IL-6. Conclusion: Neuroinflammation and oxidative stress may have prognostic values in brain-injured patients, in particular IL-6. Neurosurgical procedures may decrease the neuroinflammation process

Correlation of hypoxia inducible factor-1α and vascular endothelium growth factor in rat myocardium during aerobic and anaerobic exercise.

Background: Exercise increases the need for oxygen to generate ATP through oxidative phosphorylation. If the high energy demand during exercise is not balanced by sufficient oxygen supply, hypoxia occurs in skeletal muscle tissue leading to upregulation of hypoxia inducible factor-1α (HIF-1α). The activity of HIF-1α increases the expression of various genes in order to reduce the metabolic dependence on oxygen and to increase oxygen supply to the tissue, e.g., VEGF which plays a role in angiogenesis. In myocardium, it is unclear whether exercise leads to hypoxia and whether HIF-1α and VEGF play a role in the mechanism of hypoxic adaptation. This study aimed to investigate the correlation of HIF-1α and VEGF in heart muscle tissue of rats during aerobic and anaerobic exercise. Methods: A rat treadmill was used with a specific exercise program for 1, 3, 7 and 10 days. The concentrations of HIF-1α and VEGF were measured the myocardium. Results: Both, HIF-1α protein and VEGF were increased (p < 0.05) in the groups with aerobic and anaerobic exercise. Concentrations of HIF-1α were highest on the first day of activity, being higher in the anaerobic than in the aerobic group (156.8 ± 33.1 vs. 116.03 ± 5.66). Likewise, the highest concentration of VEGF in the group with anaerobic exercise occurred on the first day (36.37 ± 2:35), while in the aerobic group, VEGF concentration was highest on day 3 (40.66 ± 1.73). The correlation between the myocardial tissue consentrations of HIF-1α and VEGF is moderate (r = 0.59) in the aerobic group and strong in the anaerobic group (r = 0.69). Conclusion: Aerobic and anaerobic exercise increase HIF-1α and VEGF concentrations in rat myocardium in specific patterns. The anaerobic condition triggers vascularization stronger and obviously earlier than aerobic exercise.

Schizonticidal effect of a combination of Amaranthus spinosus L. and Andrographis paniculata Burm. f./Nees extracts in Plasmodium berghei-infected mice.

Background: Amaranthus spinosus and Andrographis paniculata are traditionally used as antimalarial herbs, but the combination of both has not yet been tested. The aim of this study was to determine the schizonticidal anti-malaria effect of a combination in Plasmodium berghei-infected mice. Methods: Male mice (Balb/c strain) weighing 28-30 g, 7-8 weeks old, were randomly devided into 5 groups of 4 animals each. Group A: controls (nil) and 4 treatment groups (B, C, D, and E). Group B: Amarathus 10 mg/kgBW, group C: Andrographis 2 mg/kgBW, group D: combination of Amaranthus + Andrographis 10 mg + 2 mg/kgBW. All treatment with plant extracts was administered orally, once per day for 7 days. Group E was given chloroquine 10 mg/kgBW, once a day orally, for 3 days. Results: The body weigh increased only in group D, hemoglobin concentration increased significantly vs controls (p < 0.05) in treatment groups C, D, and E, and blood schizonticidal activity was seen in all treatment groups, highest at almost 90% in groups D and E. Survival rate was 100% in all groups. Conclusion: The combination of Amaranthus and Andrographis (10 mg + 2 mg/kgBW) exerts the same blood schizonticidal activity as chloroquine 10 mg/kgBW.

Plasma lipid pattern and red cell membrane structure in β-thalassemia patients in Jakarta.

Background: Over the last 10 years, we have investigated thalassemia patients in Jakarta to obtain a comprehensive picture of iron overload, oxidative stress, and cell damage. Methods: In blood samples from 15 transfusion-dependent patients (group T), 5 non-transfused patients (group N) and 10 controls (group C), plasma lipids and lipoproteins, lipid-soluble vitamin E, malondialdehyde (MDA) and thiol status were measured. Isolated eryhtrocyte membranes were investigated with electron paramagnetic resonance (EPR) spectroscopy using doxyl-stearic acid and maleimido-proxyl spin lables. Data were analyzed statistically with ANOVA. Results: Plasma triglycerides were higher and cholesterol levels were lower in thalassemic patients compared to controls. Vitamin E, group C: 21.8 vs T: 6.2 μmol/L) and reactive thiols (C: 144 vs. T: 61 μmol/L) were considerably lower in transfused patients, who exert clear signs of oxidative stress (MDA, C: 1.96 vs T: 9.2 μmol/L) and of tissue cell damage, i.e., high transaminases plasma levels. Non-transfused thalassemia patients have slight signs of oxidative stress, but no signifi cant indication of cell damage. Erythrocyte membrane parameters from EPR spectroscopy differ considerably between all groups. In transfusion-dependent patients the structure of the erythrocyte membrane and the gradients of polarity and fl uidity are destroyed in lipid domains; binding capacity of protein thiols in the membrane is lower and immobilized. Conclusion: In tranfusion-dependent thalassemic patients, plasma lipid pattern and oxidative stress are associated with structural damage of isolated erythrocyte membranes as measured by EPR spectroscopy with lipid and proteinthiol spin labels.

Application of α-lipoic acid beyond peripheral diabetic polyneuropathy (A report of 3 cases).

Background: In Germany, lipoic acid is registered with the indication of “peripheral diabetic polyneuropathy”. This report intends to demonstrate therapeutic activity beyond this indication. In Indonesia, the substance is not registered for therapy. Methods: Three patients (two of them in Germany and one in Indonesia) with pathoneurological symptoms different from peripheral diabetic polyneuropathy were treated with α-lipoic acid: i) post-borelliosis infl ammation with arthritic and paraesthetic symptoms, ii) post-operative (mamma carcinoma) and post-chemotherapeutic sensoric and motoric neural deficits occurring in parallel with additional radiation therapy, and iii) post-traumatic (cerebral) and postoperative (brain surgery) cardiovascular and pulmonary crisis with broad pathoneurological (sensoric and motoric, visual, auditory) deficits and dysarthria. Results: All three patients improved in close correlation with the onset and continuation of lipoic acid intake, whereas other therapeutic measures did not appear very successful. It cannot be ruled out that the other therapeutic regimens applied interacted with lipoic acid in a supporting additive or synergistic manner, because three cases as reported here do not allow for such conclusion; however, separately, or with interaction, lipoic acid helped the patients to recover from their pathoneurological symptoms in the meaning of the traditional medical term “restitutio ad integrum”. Conclusion: In the three cases in this study, lipoic acid was effective in therapy of pathoneurological symptoms different from peripheral diabetic neuropathy. Further confirmative studies are suggeted.