Thymoquinone ameliorates symptoms of Parkinson's disease in a 6-OHDA rat model by downregulation of miR-204-3p.

microRNAs (miRNAs) play a significant role in the pathophysiology of Parkinson's disease. In this study, we evaluated the neuroprotective effect of thymoquinone on the expression profiles of miRNA and cognitive functions in the 6-hydroxydopamine (6-OHDA)-induced Parkinson's model. Male adult Wistar albino rats (200-230 g, n  = 36) were randomly assigned to six groups: Sham, thymoquinone (10 mg/kg, p.o.), 6-OHDA, 6-OHDA + thymoquinone (10 mg/kg), 6-OHDA + thymoquinone (20 mg/kg), and 6-OHDA + thymoquinone (50 mg/kg). Behavioral changes were detected using the open field and the elevated plus maze tests. The mature 728 miRNA expressions were evaluated by miRNA microarray (GeneChip miRNA 4.0). Ten miRNAs were selected (rno-miR-212-5p, rno-miR-146b-5p, rno-miR-150-5p, rno-miR-29b-2-5p, rno-miR-126a-3p, rno-miR-187-3p, rno-miR-34a-5p, rno-miR-181d-5p, rno-miR-204-3p, and rno-miR-30c-2-3p) and confirmed by real-time PCR. Striatum samples were stained with hematoxylin-eosin to determine the effect of dopaminergic lesions. One-way ANOVA test and independent sample t -test were used for statistical analyses. rno-miR-204-3p was upregulated at 6-OHDA and downregulated at the 50 mg/kg dose of thymoquinone. In conclusion, thymoquinone at a dose of 50 mg/kg ameliorates symptoms of Parkinson's disease in a 6-OHDA rat model by downregulation of miR-204-3p. Also, the results showed that thymoquinone can improve locomotor activity and willing exploration and decreased anxiety. Therefore, thymoquinone can be used as a therapeutic agent.

The Role of Glycogen Synthase Kinase-3ß in the Zinc-Mediated Neuroprotective Effect of Metformin in Rats with Glutamate Neurotoxicity.

Metformin has been suggested to have protective effects on the central nervous system, but the mechanism is unknown. The similarity between the effects of metformin and the inhibition of glycogen synthase kinase (GSK)-3ß suggests that metformin may inhibit GSK-3ß. In addition, zinc is an important element that inhibits GSK-3ß by phosphorylation. In this study, we investigated whether the effects of metformin on neuroprotection and neuronal survival were mediated by zinc-dependent inhibition of GSK-3ß in rats with glutamate-induced neurotoxicity. Forty adult male rats were divided into 5 groups: control, glutamate, metformin + glutamate, zinc deficiency + glutamate, and zinc deficiency + metformin + glutamate. Zinc deficiency was induced with a zinc-poor pellet. Metformin was orally administered for 35 days. D-glutamic acid was intraperitoneally administered on the 35th day. On the 38th day, neurodegeneration was examined histopathologically, and the effects on neuronal protection and survival were evaluated via intracellular S-100ß immunohistochemical staining. The findings were examined in relation to nonphosphorylated (active) GSK-3ß levels and oxidative stress parameters in brain tissue and blood. Neurodegeneration was increased (p < 0.05) in rats fed a zinc-deficient diet. Active GSK-3ß levels were increased in groups with neurodegeneration (p < 0.01). Decreased neurodegeneration, increased neuronal survival (p < 0.01), decreased active GSK-3ß (p < 0.01) levels and oxidative stress parameters, and increased antioxidant parameters were observed in groups treated with metformin (p < 0.01). Metformin had fewer protective effects on rats fed a zinc-deficient diet. Metformin may exert neuroprotective effects and increase S-100ß-mediated neuronal survival by zinc-dependent inhibition of GSK-3ß during glutamate neurotoxicity.

Deep phenotyping of miRNAs in exercise-induced cardiac hypertrophy and fibrosis.

Cardiac hypertrophy (CH) is an adaptational enlargement of the myocardium, in exposure to altered stress conditions or in case of injury which can lead to heart failure and death. MicroRNAs (miRNAs) are noncoding RNAs that play a significant role in modulating gene expression. Here, we aimed to identify new miRNAs effective in an experimental CH model and to find an epigenetic biomarker that could demonstrate therapeutic targets responsible for the pathology of heart tissue and serum. In this study, Sprague-Dawley male rats were divided into the training group (TG, n=9) and the control group (CG, n=6). Systolic and diastolic dimensions of the left ventricle and myocardial wall thickness were measured by echocardiography to assess CH. After the exercise program of the rats, miRNA expression measurements and histological analyses were performed. The 25,000 genes in the rat genome were searched using microarray analysis. A total of 128 miRNAs were selected according to the fold change rates, and nine miRNAs were validated for expression analysis. The terminal deoxynucleotidyl transferase dUTP nick (TUNEL) method was used to detect apoptotic cells. Cell proliferation was evaluated by the proliferative cell nuclear antigen (PCNA) method. Necrosis, bleeding, and intercellular edema were detected in TG. The mean histopathological score was higher in TG (p=0.03). There were rarely positive cells for apoptosis of both groups in cardiomyocytes. In the receiver characteristic curve analysis (ROC), the heart tissue rno-miR-290 had an area under the curve (AUC) of 0.920 with 100% sensitivity and 89.90% specificity (p=0.045), rno-miR-194-5p had AUC of 0.940 with 83.33% sensitivity and 100% specificity (p=0.003), and the serum rno-miR-132-3p AUC was 0.880 with 66.67% sensitivity and 100% specificity (p=0.004) in TG. miR-194-5p was used as a therapeutic target for remodeling the cardiac process. While miR-290 contributes to CH as a negative regulator, miR-132 in serum is effective in the pathological and physiological cardiac remodeling process and is a candidate biomarker.

The effects of sigma-1 agonist fluvoxamine on experimental induced tardive dyskinesia model in rats.

Tardive dyskinesia (TD) is a persistent involuntary complex movement disorder that is known to occur with long-term antipsychotic treatment. Despite being a well-recognized complication of this treatment, its symptoms are often masked by the antipsychotic agents, only to become apparent upon reducing or terminating the treatment. In an effort to advance our understanding of TD pathophysiology and to identify potential therapies, the current study aimed to establish an animal model of TD by administering haloperidol to rats and to evaluate the efficacy of fluvoxamine, a selective serotonin reuptake inhibitor (SSRI), in ameliorating TD symptoms. The study compared the behavioral and biochemical parameters of rats that were treated with either fluvoxamine, tetrabenazine, haloperidol, or saline (control group). The biochemical parameters of interest included the brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), superoxide dismutase (SOD), and malondialdehyde (MDA). To achieve the study objectives, 32 male Wistar Albino rats were assigned to four different groups. The control group received physiological saline for six weeks. The haloperidol group received 1 mg/kg/ip haloperidol for the first three weeks, followed by two weeks of saline. The haloperidol+fluvoxamine group received 1 mg/kg/ip haloperidol for the first three weeks, followed by 30 mg/kg/ip fluvoxamine. The haloperidol+tetrabenazine group was administered 1 mg/kg/ip haloperidol for the first three weeks, followed by 5 mg/kg/ip tetrabenazine. Behavioral assessments of the rats were performed by measuring vacuous chewing movements. Subsequently, samples were collected from the hippocampus, striatum, and frontal lobe tissues of the rats, and BDNF, NGF, SOD, and MDA levels were measured. The results of the study demonstrated significant differences between the groups with respect to behavioral observations. Furthermore, SOD levels in the hippocampus, as well as BDNF, NGF, and SOD levels in the striatum of the haloperidol+fluvoxamine group were significantly higher than those observed in the haloperidol group. Conversely, MDA levels in the hippocampus were significantly lower in the haloperidol+fluvoxamine group than in the haloperidol group. These findings provide evidence of the beneficial effects of fluvoxamine, acting as a sigma-1 agonist, in treating TD symptoms induced experimentally. The observed benefits were supported by the biochemical investigations performed on brain tissue samples. Therefore, fluvoxamine may be considered as a potential alternative treatment for TD in clinical practice, although further research is needed to corroborate these findings.

Caloric restriction and redox homeostasis in various regions of aging male rat brain: Is caloric restriction still worth trying even after early-adulthood?: Redox homeostasis and caloric restriction in brain.

Despite recent studies have shown that caloric restriction (CR) could improve some functional loss associated with brain aging, the biochemical effects of CR on brain aging are still not well understood on a quantifiable biochemical basis, including whether CR could be protective when started around middle adulthood, when age-related neurodegenerative diseases are thought to set in. Therefore, in the light of more than ever aging societies and increasing neurodegenerative diseases, we aimed to test the biochemical effects of CR on redox homeostasis in different parts of male Sprague-Dawley rat brain by using the biomarkers we consistently validated in our previous work (TOS, PCO, AOPP, AGEs, sRAGE, P-SH, LHPs, 4-HNE, TAS, Cu, Zn-SOD). Our results indicate that oxidative stress biomarkers are lower in CR group, implying a more favorable redox status that has been previously shown to be correlated with better neural function. PRACTICAL APPLICATIONS: We report that the beneficial effects of caloric restriction (CR) on various brain tissues result in significant improvements in biochemical markers, even though CR is not started in early adulthood. Hence, our select age group provides a sound redox status-related neurochemical understanding for many recent CR studies, where a functional loss was detected at this age.

The effects of lipoic acid on redox status in brain regions and systemic circulation in streptozotocin-induced sporadic Alzheimer's disease model.

While the deterioration of insulin-glucose metabolism (IGM), impaired redox homeostasis (IRH), ß-amyloid accumulation was reported in Sporadic Alzheimer's Disease (SAD) model, aforementioned factors related to lipoic acid administration and anthropometric indexes (AIs) are not yet studied with integrative approach. ß-amyloid accumulation, redox homeostasis biomarkers and AIs are investigated in SAD model. Streptozotocin-induced inhibition of insulin-signaling cascade but not GLUT-2 and GLUT-3 transporters takes a role in ß-amyloid accumulation. Inhibition types are related to IRH in cortex, hippocampus and systemic circulation. Lipoic acid (LA) shows both antioxidant and prooxidant effect according to the anatomical location. LA administration also leads to improved AIs during GLUT-2 inhibition and cortical redox status in GLUT-3 inhibited group. Optimal LA action could be possible if its redox behavior is balanced to antioxidant effect. Diagnostic usage of systemic IRH parameters as biomarkers and their possible correlations with deteriorated IGM should be investigated. Graphical abstract ᅟ.

Interaction of Cocaine- and Amphetamine-regulated Transcript and Neuropeptide Y on Behavior in the Central Nervous System.

INTRODUCTION: In the central nervous system, cocaine- and amphetamine-regulated transcript (CART) 55-102 peptide is localized in areas, such as the ventral tegmental area, amygdala, hypothalamus, and hippocampus, where emotional activity is regulated. Studies on the effects of the intracerebroventricular (ICV) administration of CART peptide on behavior remain limited. The findings from these studies suggest that this neuropeptide has anxiogenic-like effects. In the central nervous system, neuropeptide Y (NPY) has similar localization as CART. Previous behavioral studies have demonstrated that the ICV administration of NPY has anxiolytic-like effects. METHODS: In our study, we established five experimental groups of male Wistar rats to study the competitive effects of NPY and CART peptide. These groups were sham (n=10), CART (n=10), NPY (n=10), CART-NPY (n=10), and NPY-CART (n=10). The open field test, elevated plus maze test, and Porsolt swim test were performed for behavioral analyses. Moreover, the rats were decapitated after the behavioral tests, and the amount of these two peptide in their brains was quantified. RESULTS: Our study revealed that the ICV administration of CART peptide is anxiogenic and inhibits animals undergoing learned helplessness in the Porsolt swim test. When we evaluated the results of our study with respect to NPY, we observed its anxiolytic-like effects; in the Porsolt swim test, although it reduced the duration of immobilization, it did not affect the period of struggle. CONCLUSION: Our results revealed that during the competitive interaction of these two peptides, anxiogenic CART peptide suppressed the anxiolytic effects of NPY.

In Vitro Fertilization, Levels of Pro-Inflammatory Factors and Lipid Peroxidation.

BACKGROUND: Infertility is a problem concerning 10-15% of the individuals in the fertile period. This study investigated effects of proinflammatory factors as well as lipid hydroperoxides (LPO) levels upon in vitro fertilization (IVF) success. MATERIALS AND METHODS: In this prospective, non-randomized, controlled clinical study, sera obtained from 26 fertile (group-1), 26 infertile women before (group-2) and after (group-3) IVF treatment were analyzed. Leptin, leptin receptor, resistin, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) were analyzed using enzyme-linked immunosorbent assay (ELISA). LPO was determined spectrophotometrically. Mann- Whitney U test, paired samples t test, Wilcoxon signed-rank test as well as Pearson correlation analysis by SPSS were performed for statistical analysis. RESULTS: TNF-α, resistin and LPO levels increased (P=0.020, P=0.003, P=0.001, respectively) in group-3 compared to group-2. A significant increase in LPO was noted both in group-2 and -3 compared to controls (P=0.000). LPO were higher in non-pregnants than pregnants in group-2. For pregnants, significant correlations were observed between leptin and resistin in group-2 and TNF-α and leptin in group-3. None of these correlations were found for the women, who could not conceive. CONCLUSION: LPO, leptin-resistin correlation, associations with TNF-α may be helpful during the interpretation of IVF success rates.

Age-related changes in rat prostate tissue; perspective of protein oxidation.

BACKGROUND: Increased systemic oxidative stress is considered as an important risk factor for prostate cancer occurrence; however, the relationship between impaired redox homeostasis of prostate tissue and aging remains unclear. OBJECTIVE: In our study, we hypothesized that age-related deterioration of redox homeostasis in prostate tissue may be considered as a predisposing factor for prostate cancer occurrence. METHODS: Sprague-Dawley rats were divided into two groups as young control (5 months) and naturally aged (24 months). We investigated the levels of oxidant and antioxidant parameters in prostate tissue. RESULTS: Advanced oxidation protein products, protein carbonyl, non-protein thiol and lipid hydroperoxides levels of aged rats were significantly higher than in the young control rats (p < 0.01, p < 0.05, p < 0.001, p < 0.05, respectively). Additionally, antioxidant activity of Cu-Zn-superoxide dismutase in elderly group was significantly lower than young controls (p < 0.05). CONCLUSIONS: We suggest that increased non-protein thiol levels found in aged rats may prevent further dissemination of oxidative protein damage. We also propose that the increased levels of oxidative protein damage markers and decreased Cu-Zn superoxide dismutase activity in aged prostate may be considered as a predisposing factor for prostate cancer. Further studies are warranted to clarify all these oxidative changes as initiation factors for prostate cancer in the association of aging with prostate cancer.

A comprehensive study of myocardial redox homeostasis in naturally and mimetically aged rats.

Age-related myocardial dysfunction has important implications with impaired redox homeostasis. Current study focused on investigation of redox homeostasis and histopathological changes in the myocardium of mimetically (MA), naturally aged (NA), and young control (YC) rats. Chronic D-galactose administration to young male Wistar rats (5 months old) was used to set up experimental aging models. We investigated 16 different oxidative damage biomarkers which have evaluated redox homeostasis of cellular macromolecules such as protein, lipid, and DNA. As a protein oxidation biomarker, advanced oxidation end products, protein carbonyl groups, protein-bound advanced glycation end products, dityrosine, kynurenine, and N-formylkynurenine concentrations in MA and NA rats were found to be significantly higher compared to those in YC rats. On the other hand, the levels of protein thiol groups were not significantly different between groups, whereas lipid peroxidation biomarkers such as conjugated diens, lipid hydroperoxides, and malondialdehyde in MA and NA rats were found to be significantly higher in comparison to those in YCs. For the assessment of oxidative DNA damage, we analyzed eight hydroxy-5'-deoxyguanosine concentrations of MA and NA groups which were higher than YCs. As an antioxidant status in the MA and NA groups, Cu-Zn superoxide dismutase, ferric reducing antioxidant power, and total thiol levels were lower than those in the YCs. Only nonprotein thiol levels were not significantly different. We also observed similar histopathological changes in MA and NA rats. We concluded that the mimetic aging model could be considered as a reliable experimental model for myocardial senescence.

Regular aerobic training combined with range of motion exercises in juvenile idiopathic arthritis.

OBJECTIVE: To assess the effects of regular aerobic training combined with range of motion (ROM) exercises on aerobic capacity, quality of life, and function in children with juvenile idiopathic arthritis (JIA). METHODS: Thirty patients with JIA and 20 healthy age-matched controls (mean age ± SD, 11.3 ± 2.4 versus 11.0 ± 2.3, resp.; P > 0.05) were included. All patients performed aerobic walking (4 days a week for 8 weeks) and active and passive ROM exercises of involved joints. All patients completed the childhood health assessment questionnaire (CHAQ) and the child health questionnaire. ROM measurements of joints were performed by using universal goniometer. Aerobic capacity was determined by measuring peak oxygen uptake (VO2peak) during an incremental treadmill test. RESULTS: Peak oxygen uptake and exercise duration were significantly lower in JIA group than in controls (32.5 ± 6.6 versus 35.9 ± 5.8 and 13.9 ± 1.9 versus 15.0 ± 2.0, resp.; P < 0.05 for both). Eight-week combined exercise program significantly improved exercise parameters of JIA patients (baseline versus postexercise VO2peak and exercise duration, 32.5 ± 6.6 to 35.3 ± 7.9 and 13.9 ± 1.9 to 16.3 ± 2.2, resp.; P < 0.001 for both). Exercise intervention significantly improved CHAQ scores in JIA patients (0.77 ± 0.61 to 0.20 ± 0.28, P < 0.001). CONCLUSION: We suggest that regular aerobic exercise combined with ROM exercises may be an important part of treatment in patients with JIA.

Association of fetuin A, adiponectin, interleukin 10 and total antioxidant capacity with IVF outcomes.

BACKGROUND: Possible roles of anti-inflammatory factors as well as total antioxidative capacity in reproductive processes of women undergoing in vitro fertilization (IVF) are still being investigated and the contributions by some of them remain controversial. OBJECTIVE: The aim of this study is to investigate the relationship between anti-inflammatory parameters and total antioxidative capacity (TAC) of the body during IVF. In this respect, adiponectin, interleukin-10 (IL-10), interleukin-1 receptor antagonist (IL-1RA), fetuin A and TAC analyses have been performed. MATERIALS AND METHODS: In this prospective, non-randomized, controlled clinical study, sera obtained from 26 fertile (Group-1), and 26 infertile women before (Group-2) and after (Group-3) IVF treatment were analyzed. IL-1RA, IL-10, fetuin A, adiponectin and insulin were determined by ELISA. TAC was determined spectrophotometrically. Mann-Whitney U test, paired sample t-test, Wilcoxon signed-rank test as well as Pearson correlation analysis by SPSS were performed for statistical analysis. RESULTS: Clinical pregnancy and live birth rates were determined as 30.8% and 23.1%, respectively, in pregnant group. For the pregnant, significant indirect correlations were detected between fetuin A and adiponectin (r=-0.843; p=0.035) as well as IL-10 (r=-0.846; p=0.034) in Group 2. The correlation between adiponectin and IL-10 doubled in pregnant compared to non-pregnant (r=0.929; p=0.007 vs. r=0.478; p=0.033). The correlations between fetuin A and TAC in pregnant were noted both in Group 2 (r=0.892; p=0.017) and Group 3 (r=0.875; p=0.022). No correlation of fetuin A with these parameters was detected in non-pregnant group. CONCLUSION: Fetuin A, TAC, IL-10, adiponectin and their associations may be important from their predictive values for IVF success point of view. Parameters with anti-inflammatory or antioxidant property appear to improve pregnancy in women undergoing IVF.

Pallidal deep brain stimulation in a 5-year-old child with dystonic storm: case report.

A 5-year-old child had a medical history of epilepsy and a newly presented mental retardation with a life-threatening dystonic storm. Neuroimagings showed bilateral calcification of the pallidum. Several treatment modalities were performed, but the symptoms showed no significant improvement. The patient was operated on in order to place a deep brain stimulation (DBS) targeting bilateral globus pallidum internus (GPi). The dystonia showed a remarkable improvement after surgery, with 81% reduction of dystonia severity after 15 months. To our best knowledge, this is the youngest patient mentioned in the literature to be treated with DBS, which was also life-saving in this case.

Unilateral thalamic Vim and GPi stimulation for the treatment of Holmes' tremor caused by midbrain cavernoma: case report and review of the literature.

A 30-year-old man with brainstem cavernoma experienced hemorrhage and was operated in 2008. Six months after the operation, the patient presented with new complaints of left arm tremor namely Holmes' tremor. Neurological examination also revealed left-sided internuclear ophthalmoplegia, left-sided mild paresis, and increased deep tendon reflexes of the left upper extremity, truncal ataxia, and dysarthria. Brain magnetic resonance imaging showed a postoperative cavity and gliosis at the level of the superior and inferior colliculus in the right tegmentum and right red nucleus with extension to the substantia nigra. Fahn-Tolosa-Marin tremor rating scale (TRS) for his left upper extremity (Part A, score 6) was 11 for the proximal and the distal arm. After the failure of medical treatment, the patient underwent right globus pallidum internus and ventral intermediate thalamic nucleus deep brain stimulation. There were no side effects related to the stimulation. Final TRS months after operation was 3 for the proximal and 4 for the distal arm.

Alterations of central hypercapnic respiratory response induced by acute central administration of serotonin re-uptake inhibitor, fluoxetine.

Long-term neurochemical changes are responsible for therapeutic actions of fluoxetine. The role of increased central concentration of serotonin by inhibiting its re-uptake via fluoxetine on the central hypercapnic ventilatory response is complex and little is known. We aimed to research the effect of acute intracerebroventricular (ICV) injection of fluoxetine on hypercapnic ventilatory response in the absence of peripheral chemoreceptor impulses and the role of 5-HT2 receptors on responses. Eighteen anesthetized albino rabbits were divided as Fluoxetine and Ketanserin groups. For ICV administration of fluoxetine and ketanserin, a cannula was placed in the left lateral ventricle by the stereotaxic method. Respiratory frequency (fR), tidal volume (V(T)) and ventilation minute volume (V(E)) were recorded in both groups. ICV fluoxetine (10.12 mmol/kg) injection during normoxia caused significant increases in V(T) and V(E) (both P < 0.01) in the fluoxetine group. When the animals were switched to hypercapnia f/min, V(T) and V(E) increased significantly. The increases in percentage values in V(T) and V(E) in Fluoxetine + Hypercapnia phase were higher than those during hypercapnia alone (P < 0.01 and P < 0.05, respectively). On blocking of 5-HT2 receptors by ketanserin (0.25 mmol/kg), the ventilatory response to Fluoxetine was abolished and the degree of increases in V(T) and V(E) in the Ketanserin + Hypercapnia phase were lower than those during hypercapnia alone (P < 0.01 and P < 0.001, respectively). We concluded that acute central fluoxetine increases normoxic ventilation and also augments the stimulatory effect of hypercapnia on respiratory neuronal network by 5-HT2 receptors in the absence of peripheral chemoreceptor impulses.

Protein and DNA oxidation in different anatomic regions of rat brain in a mimetic ageing model.

It has been reported that d-galactose administration causes an increase in oxidative and osmotic stresses in several tissues of rodents. In this study, we established a brain ageing model by using d-galactose and investigated the concentrations of oxidative stress markers on the hippocampus, parietal and frontal lobes of male Sprague-Dawley rats. A mimetic ageing model was established by injecting d-galactose (60 mg/kg/day/i.p.) in the experimental group for 42 days. At the end of this period, we tested spatial memory using the Morris water maze test. To investigate the magnitude of oxidative damage in proteins, lipids and DNA, we studied the concentrations of various oxidative stress parameters in the hippocampus, parietal and frontal lobes of the brain. Glial and neuronal cell oxidative damage was observed in each of the three anatomic regions. It was found that protein carbonyl groups and advanced oxidation product concentrations in the d-galactose applied group were significantly high in each of the three brain lobes compared with the control group. Thiol concentration was found to be decreased in the parietal lobe. A concurrent increase in lipid hydroperoxides was also observed in this lobe. On the other hand, 8-hydroxy-2'-deoxyguanosine concentration was significantly increased in the hippocampal lobe of rats in the experimental group when compared with the controls. The results obtained from the mimetic ageing model rats showed that various anatomical regions of brain have different susceptibility to oxidative damage of proteins, lipids and DNA.

Treatment of homocystinuria-related dystonia with deep brain stimulation: a case report.

A 23-year-old woman with the medical history of homocystinuria that had been diagnosed at the age of 14 has been non-responsive to treatment. The patient presented with the symptoms of dysphonia, dysarthria and severe dystonia of the neck and left extremities. Blood and urine biochemistry revealed high levels of homocystine. Brain magnetic resonance imaging was normal with no detectable pathologies. Medical treatment strategies were used and repeated injections of botulinum toxin A were administered, but the symptoms showed no significant improvement. The patient was then operated, and deep brain stimulators targeting the bilateral globus pallidus internus were implanted. After the activation of the electrodes, dystonia symptoms showed a remarkable improvement. Good outcome was documented during the follow-up period of 7 months. To our best knowledge, this is the first reported case of homocystinuria-related dystonia symptoms that were successfully treated with deep brain stimulation.

Influence of intermittent hypobaric exposure on SOD and TBARS levels in trained rats.

Live high train low (LHTL) is a well-known training model for preparation of competitions. In this study, the thiobarbituric acid reacting substances (TBARS) levels and superoxide dismutase (SOD) activity were determined in heart, lung and muscle tissues of rats. They were intermittently exposed to hypobaric pressure of 523 mmHg, corresponding to an altitude of 3,000 m, and they performed swim training at sea level. Two groups of male rats were trained to swim for thirty minutes a day and 4 days a week, lasting 9 weeks. Two groups were exposed to hypobaria for 120 min a day and 4 days a week for 9 weeks in pressure cabin. In heart tissue, TBARS levels of normobaric trained (NbT) group was higher (P < 0.05) than those of the normobaric sedentary (control) group. TBARS levels of hypobaric trained (HbT) group was higher than those of the control and hypobaric sedentary (Hb) groups (P < 0.001; P < 0.01, respectively). TBARS levels of lung tissue of HbT group was also higher than those of the same groups (control; P < 0.01, Hb; P < 0.05, respectively). In muscle tissue, TBARS levels of HbT group was higher than those of the sedentary groups (control; P < 0.001, Hb; P < 0.05, respectively). SOD activity of heart tissue of HbT group was higher (P < 0.001) than that of the other groups. In lung tissue, SOD activity of control group was lower than that of the other groups (HbT; P < 0.001, NbT; P < 0.01, Hb; P < 0.01, respectively). In muscle tissue, SOD activity of HbT group was higher (P < 0.01) than that of the control group. The results of this study suggest that intermittent hypobaric exposure may augment exercise-induced oxidative stress in heart, lung and muscle of trained rats.

Intraventricular albumin: an optional agent in experimental post-traumatic brain edema.

HYPOTHESIS: Human albumin may be effective in the treatment of posttraumatic brain edema due to its hyperoncotic features. Therefore, the aim of the experimental study presented in this paper has two points: the first is to evaluate the efficacy of intraventricular hyperoncotic human albumin on post-traumatic brain edema and the second is to try to show the appropriate posttraumatic time window for albumin administration. METHOD: Traumatic brain injury and subsequent edema was formed by a model of impact acceleration injury in rats. Human albumin was administered via intraventricular route by using a stereotactic head holder. All animals in each group were decapitated 24 hours after the procedure and the effect of albumin was evaluated by measurement of tissue specific gravity. RESULTS: Tissue specific gravity decreased in edematous tissue (trauma indicator), increased after albumin administration at the 12th (p < 0.001), and both at the 1st and 12th hour of the trauma (edema treatment; p < 0.001). On the other hand, albumin administered at the 12th, and at both the 1st and 12th hours in the rats without trauma has caused the formation of the brain edema. CONCLUSION: We conclude that human albumin is effective in cytotoxic, but not in vasogenic edema and exerts its best anti-edematous effect at the 12th hour of severe head trauma and this study may help future studies that will try to show the effects of albumin with different time modalities after severe head injury.