Biomarkers of Alzheimer′s Disease in the Cerebrospinal Fluid of Spanish Patients With Mild Cognitive Impairment

The study of biomarkers in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) is a technique used with increasing frequency in the early diagnosis of Alzheimers disease (AD). Our objectiv was to gain an own experience while evaluating the reliability, sensitivity, and reproducibility of this technique in Spanish patients. Thirty-seven patients with MCI and twenty-four control subjects were studied by means of AD biomarker analysis in CSF. xMAP Luminex and INNO-BIA Alzbio3 reagents of Innogenetics were used. The study variables assessed were levels of Aβ_1–42, T-tau and P-tau_181p proteins as well as the ratios of T-tau/Aβ_1–42 and P-tau_181p/Aβ_1–42. Samples from nineteen patients were examined twice. Intra-class correlation coefficients for the three biomarkers used showed values higher than 0.95. We observed significant differences between the control group and the MCI groups. In the 6 months following lumbar puncture (LP), eleven (29%) patients with MCI developed AD. These patients showed significant lower levels in Aβ_1–42 protein (276.35 ± 78 vs. 367.13 ± 123.49, P < 0.03) and higher ratios (T-tau/Aβ_1–42 [0.38 ± 0.2 vs. 0.22 ± 0.14, P < 0.01] and P-tau_181p/Aβ_1–42 [0.27 ± 0.13 vs. 0.16 ± 0.1, P < 0.008]) to those in the same group who remained stable. We obtained similar results to those in the most recent reliable literature with our ROC curves, especially with our P-tau_181p values and T-tau/Aβ_1–42 ratio in order to differentiate between control and AD groups. Our experience showed that the analysis of CSF-AD biomarkers in patients with MCI is reliable, sensitive and reproducible. In our knowledge, this is the first experience in Spanish patients.     

Cerebrospinal Fluid Levels of Amyloid Precursor Protein Are Associated with Ventricular Size in Post-Hemorrhagic Hydrocephalus of Prematurity

Background

Neurological outcomes of preterm infants with post-hemorrhagic hydrocephalus (PHH) remain among the worst in infancy, yet there remain few instruments to inform the treatment of PHH. We previously observed PHH-associated elevations in cerebrospinal fluid (CSF) amyloid precursor protein (APP), neural cell adhesion molecule-L1 (L1CAM), neural cell adhesion molecule-1 (NCAM-1), and other protein mediators of neurodevelopment.

Objective

The objective of this study was to examine the association of CSF APP, L1CAM, and NCAM-1 with ventricular size as an early step toward developing CSF markers of PHH.

Methods

CSF levels of APP, L1CAM, NCAM-1, and total protein (TP) were measured in 12 preterm infants undergoing PHH treatment. Ventricular size was determined using cranial ultrasounds. The relationships between CSF APP, L1CAM, and NCAM-1, occipitofrontal circumference (OFC), volume of CSF removed, and ventricular size were examined using correlation and regression analyses.

Results

CSF levels of APP, L1CAM, and NCAM-1 but not TP paralleled treatment-related changes in ventricular size. CSF APP demonstrated the strongest association with ventricular size, estimated by frontal-occipital horn ratio (FOR) (Pearson R = 0.76, p = 0.004), followed by NCAM-1 (R = 0.66, p = 0.02) and L1CAM (R = 0.57,p = 0.055). TP was not correlated with FOR (R = 0.02, p = 0.95).

Conclusions

Herein, we report the novel observation that CSF APP shows a robust association with ventricular size in preterm infants treated for PHH. The results from this study suggest that CSF APP and related proteins at once hold promise as biomarkers of PHH and provide insight into the neurological consequences of PHH in the preterm infant.     

Serum and Cerebrospinal Fluid Magnesium Levels, Glasgow Coma Scores, and In-Hospital Mortality in Patients with Acute Stroke

The aim of this study was to determine the relationship between serum and cerebrospinal fluid (CSF) magnesium (Mg⁺²) levels, Glasgow Coma Scores (GCS), and 7-day mortality in acute stroke patients. Patients with acute ischemic or hemorrhagic stroke arriving within the first 3 h of symptoms were included in the study. The control group consisted of healthy volunteers. GCS was determined, and blood and CSF samples were taken in order to establish serum and CSF glucose, Mg⁺², sodium, potassium, calcium, and chlorine levels. Mortality was recorded at 7 days after admission. CSF Mg⁺² in the ischemic infarct group was significantly lower than in the control group (p = 0.006). CSF Mg⁺² in the ischemic infarct patients with a GCS ≤ 8 were significantly lower (p = 0.002) than controls and in ischemic infarct patients with a GCS ≥9. In the ischemic stroke patients, CSF Mg⁺² and GCS were significantly correlated (r = 55, p = 0.031). CSF Mg⁺² levels in ischemic stroke patients who died within 7 days were significantly lower than controls, ischemic stroke patients who survived, and hemorrhagic stroke patients who died (p = 0.002, p = 0.042, and p = 0.005, respectively). Low CSF Mg⁺² levels in patients with acute ischemic stoke at admission predicted a higher 1-week mortality.     

Contrast sensitivity in a harbor seal (<Emphasis Type="Italic">Phoca vitulina</Emphasis>)

In this study, the contrast sensitivity function (CSF) of one harbor seal was determined behaviorally in a go-/no-go-experiment at an ambient light of 0.9 lx in air. Contrast sensitivity was assessed as the reciprocal value of the threshold contrast for spatial frequencies varying between 0.03 and 1.5 cycles/deg, which were displayed with contrast ranging from 0.02 to 1 on a TFT monitor with a mean luminance of 3.8 cd/m2. The CSF of the harbor seal shows the general characteristics described for other species with a peak at an intermediate frequency, a low frequency roll-off and a high frequency cut-off towards the harbor seal’s resolution limit determined in a previous study. The position of the CSF’s peak lies at approximately 0.5 cycles/deg and adopts an absolute height of 40. These results compare well with the cat’s CSF assessed at a comparable adaptation light which might reflect similarities in lifestyle and optics.     

Treatment of Trigeminal Neuralgia with Percutaneous Glycerol Injection into Meckel’s Cavity: Experience in 4012 Patients

Percutaneous glycerol injection into Meckel’s cavity is widely used to treat trigeminal neuralgia. Reports published to date summarized clinical experiences in small or intermediately sized groups of patients. The efficacy of this procedure in a large group of patients has not been evaluated so far. From December 1983 to November 2008, patients with primary trigeminal neuralgia were treated in our clinic using percutaneous glycerol injection into Meckel’s cavity which was conducted according to the Hakanson’s anterior puncture method with some modifications. In total, 4012 patients (2205 female) with a mean age of 56.5 (23–87) years were treated. The majority of patients (99.23%) experienced unilateral pain, while a small cohort of patients (31; 0.77%) had bilateral pain. The immediate success rate of the procedure was 97.1%. There was a significant (P < 0.01) positive correlation between the presence of cerebrospinal fluid (CSF) outflow and the curative effect. Follow-up was done in 3157 patients for the period of 1–25 years. The long-term success rate was 81.18%. No serious adverse effects were observed. The procedure is very effective and applicable to a wide variety of patients with trigeminal neuralgia. The presence of CSF outflow during puncture predicts better immediate and long-term outcomes.     

Behavioral Deficit and Decreased GABA Receptor Functional Regulation in the Hippocampus of Epileptic Rats: Effect of <Emphasis Type="Italic">Bacopa monnieri</Emphasis>

In the present study, alterations of the General GABA and GABA_A receptors in the hippocampus of pilocarpine-induced temporal lobe epileptic rats and the therapeutic application of Bacopa monnieri and its active component Bacoside-A were investigated. Bacopa monnieri (Linn.) is a herbaceous plant belonging to the family Scrophulariaceae. Hippocampus is the major region of the brain belonging to the limbic system and plays an important role in epileptogenesis, memory and learning. Scatchard analysis of [³H]GABA and [³H]bicuculline in the hippocampus of the epileptic rat showed significant decrease in B_max (P < 0.001) compared to control. Real Time PCR amplification of GABA_A receptor sub-units such as GABA_Aά1, GABA_Aά5, GABA_Aδ, and GAD were down regulated (P < 0.001) in the hippocampus of the epileptic rats compared to control. GABA_Aγ subunit was up regulated. Epileptic rats have deficit in the radial arm and Y maze performance. Bacopa monnieri and Bacoside-A treatment reverses all these changes near to control. Our results suggest that decreased GABA receptors in the hippocampus have an important role in epilepsy associated behavioral deficit, Bacopa monnieri and Bacoside-A have clinical significance in the management of epilepsy.     

Up-regulation of serum- and glucocorticoid-induced protein kinase 1 in the brain tissue of human and experimental epilepsy

Several studies have shown that serum- and glucocorticoid-induced protein kinase 1(SGK1) can regulate both glutamate receptors and glutamate transporters and may participate in the regulation of neuroexcitability in neuronal diseases. In our previous study, we analyzed differential gene expression in the anterior temporal neocortex of drug-refractory epilepsy patients relative to control patients using a complementary DNA microarray and found that the SGK1 gene was up-regulated more than twofold in the brain tissues of epileptic patients. In the current study, we measured SGK1 expression in the brain tissues of humans and in an experimental model of rat epilepsy in order to explore the relationship between SGK1 expression and epilepsy. The SGK1 expression was detected in thirty human brain tissues derived from patients undergoing operation for drug-refractory epilepsy and was also detected in eight samples from autopsies. Meanwhile, we investigated SGK1 expression during the epileptic process in rats using immunofluorescence, RT-PCR and western blot analysis. SGK1 expression was enhanced in the temporal neocortex of patients with drug-refractory epilepsy and was also highly expressed in the rat brain during different phases of the epileptic process. SGK1 expression was also related with the elevation of EAAT3, which expression reduced after knockdown SGK1. These results provide new insight into the potential role of SGK1 in the pathophysiology of epilepsy.     

Up-regulation of serum- and glucocorticoid-induced protein kinase 1 in the brain tissue of human and experimental epilepsy

Several studies have shown that serum- and glucocorticoid-induced protein kinase 1(SGK1) can regulate both glutamate receptors and glutamate transporters and may participate in the regulation of neuroexcitability in neuronal diseases. In our previous study, we analyzed differential gene expression in the anterior temporal neocortex of drug-refractory epilepsy patients relative to control patients using a complementary DNA microarray and found that the SGK1 gene was up-regulated more than twofold in the brain tissues of epileptic patients. In the current study, we measured SGK1 expression in the brain tissues of humans and in an experimental model of rat epilepsy in order to explore the relationship between SGK1 expression and epilepsy. The SGK1 expression was detected in thirty human brain tissues derived from patients undergoing operation for drug-refractory epilepsy and was also detected in eight samples from autopsies. Meanwhile, we investigated SGK1 expression during the epileptic process in rats using immunofluorescence, RT-PCR and western blot analysis. SGK1 expression was enhanced in the temporal neocortex of patients with drug-refractory epilepsy and was also highly expressed in the rat brain during different phases of the epileptic process. SGK1 expression was also related with the elevation of EAAT3, which expression reduced after knockdown SGK1. These results provide new insight into the potential role of SGK1 in the pathophysiology of epilepsy.     

Selenium Concentration in Cerebrospinal Fluid Samples from a Paediatric Population

Selenium is an important trace element for brain function. Our objective was to analyse cerebrospinal fluid (CSF) selenium (Se) in 89 paediatric patients. We also studied correlations between Se and other biochemical variables (age, CSF protein concentrations and glutathione peroxidase activity and plasma Se values). Cerebrospinal fluid Se values showed a significant negative correlation with the age of patients (r = −0.476; p < 0.0001), and positive with CSF total protein concentrations and GPX activity (r = 0.446, p < 0.001; r = 0.431; p = 0.001, respectively). No association was observed between plasma and CSF Se concentrations. Median CSF Se values were 32 times lower when compared with those for plasma. In conclusion, CSF Se concentrations depend on age and total CSF protein values. The association observed between CSF Se and GPX activity suggests that Se quantification might be a reflection of some Se-dependent protein function. Cerebrospinal fluid Se values were independent of serum Se concentrations.     

Multiple sclerosis: Identification and clinical evaluation of novel CSF biomarkers

Multiple sclerosis (MS) is a neuro-inflammatory and neurodegenerative disease that results in damage to myelin sheaths and axons in the central nervous system and which preferentially affects young adults. We performed a proteomics-based biomarker discovery study in which cerebrospinal fluid (CSF) from MS and control individuals was analyzed (n = 112). Ten candidate biomarkers were selected for evaluation by quantitative immunoassay using an independent cohort of MS and control subjects (n = 209). In relapsing–remitting MS (RRMS) patients there were significant increases in the CSF levels of alpha-1 antichymotrypsin (A1AC), alpha-1 macroglobulin (A2MG) and fibulin 1 as compared to control subjects. In secondary progressive MS (SPMS) four additional proteins (contactin 1, fetuin A, vitamin D binding protein and angiotensinogen (ANGT)) were increased as compared to control subjects. In particular, ANGT was increased 3-fold in SPMS, indicating a potential as biomarker of disease progression in MS. In PPMS, A1AC and A2MG exhibit significantly higher CSF levels than controls, with a trend of increase for ANGT. Classification models based on the biomarker panel could identify 70% of the RRMS and 80% of the SPMS patients correctly. Further evaluation was conducted in a pilot study of CSF from RRMS patients (n = 36), before and after treatment with natalizumab.     

Influence of Plasma and Cerebrospinal Fluid Levels of Endothelin-1 and No in Reducing Cerebral Vasospasm after Subarachnoid Hemorrhage During Treatment with Mild Hypothermia,in a Dog Model

Using vascular heat-exchange controller implemented mild hypothermia treatment, the authors established the cerebral vasospasm model in which blood was injected twice into dog’s foramen magnum; and it was discussed the influence of the concentration of endothelin-1 and NO in blood plasma and cerebrospinal fluid through continuing treatment of mild hypothermia at different times in secondary brain vasospasm model after subarachnoid hemorrhage. Thirty healthy mongrel dogs were randomly divided into five groups; artificial cerebrospinal fluid group (group A), normal temperature control group (group C), mild hypothermia 8 h group (group H1), mild hypothermia 16 h group (group H2), and mild hypothermia 32 h group (group H3). The authors injected the artificial CSF into dog’s foramen magnum in group A while the other four groups were injected with autologous arterial blood. The normal group’s temperature maintained 38.5°C. The authors set the temperature at 33.5°C in mild hypothermia groups and this was maintained for 8, 16, and 32 h, respectively. ET-1 and NO levels in the cerebrospinal fluid and plasma were assayed in each group on days 0, 7, 14, and 21. Then the changes of the diameter of blood vessels of cerebral basilar artery and overall performance categories score in each group through application of CT angiography were recorded. In the cerebral vasospasm model which was constructed by injecting the blood to dog twice, mild hypothermia treatment, through the application of vascular heat-exchange controller, could reduce cerebral vasospasm. It was observed that the duration of the mild hypothermia is directly proportional to the longer duration of the relieving of cerebral vasospasm. The reciprocal changes observed in the levels of ET-1 and NO in cerebrospinal fluid and plasma revealed that it might be possible to reduce the cerebral vasospasm by regulating the rising amplitude of ET-1 and the decrease in NO in CSF and plasma.     

Neuroprotective Role of <Emphasis Type="Italic">Bacopa monnieri</Emphasis> Extract in Epilepsy and Effect of Glucose Supplementation During Hypoxia: Glutamate Receptor Gene Expression

The experiments were designed to study the glutamate gene expression during epilepsy in adult and hypoxic insult to brain during the neonatal period and the therapeutic role of neuroprotective supplements. We investigated the role of metabotropic glutamate-8 receptor (mGluR8) gene expression in cerebellum during epilepsy and neuroprotective role of Bacopa monnieri extract in epilepsy. We also studied the effect of NMDA receptor 1 (NMDAR1) gene expression during neonatal hypoxia and therapeutic role of glucose, oxygen and epinephrine supplementation. During epilepsy a significant down-regulation (P < 0.01) of mGluR8 gene expression was observed which was up-regulated (P < 0.05) near control level after B. monnieri treatment which is supported by Morris water maze experiment. In hypoxic neonates we observed up-regulation (P < 0.001) of the NMDAR1 gene expression whereas glucose and glucose + oxygen was able to significantly reverse (P < 0.001) the gene expression to near control level when compared to hypoxia and epinephrine treatment which was supported by open field test. Our results showed that B. monnieri treatment to epileptic rats significantly brought the reversal of the down-regulated mgluR8 gene expression toward control level. In neonatal rats, hypoxia induced expressional and functional changes in the NMDAR1 receptors of neuronal cells which is corrected by supplementation of glucose alone or glucose followed by oxygen during the resuscitation to prevent the glutamate related neuronal damage. Thus, the results suggest the clinical significance of corrective measures for epileptic and hypoxic management.     

Valproic Acid Modulates Superoxide Dismutase,Uric Acid-Independent FRAP and Zinc in Blood of Adult Epileptic Patients

We aimed to evaluate changes in antioxidant status in blood during valproate (VPA) monotherapy of adult patients with epilepsy. Antioxidant enzymes [plasma superoxide dismutase (pSOD), erythrocyte superoxide dismutase (eSOD)] and non-enzymatic indices [concentration of trace elements in serum: selenium, copper, zinc (sZn) and uric acid (UA), as well as the ferric reducing ability of plasma (FRAP) and UA-independent FRAP (UAiFRAP)] were evaluated in 21 adult patients with epilepsy and 21 healthy controls. Significant differences between the study group and controls were found for pSOD (p = 0.002) and UAiFRAP (p = 0.003). pSOD was higher, whilst UAiFRAP was lower in patients compared to controls. The activity of eSOD was higher in patients treated with VPA for a longer period (7–14 years) in comparison to controls (p = 0.001) and patients with a short period of VPA treatment (p < 0.001). Patients with uncontrolled epilepsy exhibited higher sZn than seizure-free patients (p = 0.041). Standard diet and moderate use of alcohol and/or nicotine did not exert significant effects on redox balance. We conclude that the antioxidant status of epileptic patients is modified by valproate monotherapy. The frequency of seizures and duration of VPA therapy are associated with changes of oxidative/antioxidative balance. The most sensitive and relevant parameters for antioxidative defence mechanism are pSOD, UAiFRAP and sZn.     

Preventive Role of Magnesium on Skeletal Muscle Ischemia–Reperfusion Injury—an Experimental Study

The present study aims to explore whether Mg infusion has a preventive effect on ischemia–reperfusion injury in rats. A total of 20 Sprague-Dawley-type adult male rats were used. In group 1 (control), 0.9% isotonic solution was administered. In group 2 (experiment), magnesium sulfate (0.5 mg per 100 g) was administered. Ischemia was induced for 15 min for the two groups. Magnesium (Mg), interleukin 8 (IL-8), and malondialdehyde levels were analyzed in blood, while edema, neutrophil infiltration, eosinophilia, loss of striation, and nucleolization were evaluated in histopathological examination. Mg levels in the experiment group were higher than those in the control group after ischemia–reperfusion (p < 0.05). In the control group, postischemia and postreperfusion IL-8 values were higher than preoperative values (p < 0.05). As for eosinophilia and loss of striation values, these were higher in the experiment group after ischemia–reperfusion than the values in the control group (p < 0.05). Histopathologically, Mg infusion cannot prevent the tissue injury triggered in ischemia–reperfusion periods. Eosinophilia can be one of the major and earliest markers of ischemia–reperfusion injury.     

Downregulation of hippocampal GABA after hypoxia-induced seizures in neonatal rats

This study aims to determine the expression of Gamma-aminobutyric acid (GABA) following hypoxia in neonatal rats and explore how it may increase susceptibility to epilepsy later in life. A modified model of neonatal hypoxia-induced epileptic susceptibility was simulated by 17 min of hypoxia (5% O₂ and 95% N₂) in postnatal day (P) 10 rats. Hippocampal glutamate decarboxylase (GAD) and parvalbumin (PV) during the development with or without hypoxia were examined using immunohistochemistry. No detectable neuronal loss was observed in the hippocampus either immediately or 14 days after hypoxia. During the development GAD- and PV-immunoreactivity increased substantially during P 11–13 and reached mature expression in the control rats, and decreased significantly at different time points except for a transient increase during P 11–13 in the hypoxic groups. Our study indicates that downregulation of hippocampal GABA after hypoxia-induced seizures in neonatal rats may contribute to higher epileptic susceptibility in later life.     

An Association Analysis of Reelin Gene (<Emphasis Type="Italic">RELN</Emphasis>) Polymorphisms with Childhood Epilepsy in Eastern Indian Population from West Bengal

Epilepsy is a common neurological condition characterized by unprovoked seizure attacks. Early brain developmental abnormalities involving neuronal migration and lamination are implicated in childhood epilepsy. Reelin, a neuronal-signaling molecule plays a crucial role in these migratory processes. Therefore, reelin gene (RELN), which is located on human chromosome 7q22 is considered as a potential candidate gene for childhood epilepsy. In this study, we recruited 63 patients with childhood-onset epilepsy and 103 healthy controls from West Bengal in India. Genomic DNA isolated from leukocytes of cases and control individuals were used for genotyping analysis of 16 markers of RELN. Case–control analysis revealed significant over-representation of G/C and (G/C+C/C) genotypes, and C allele of exon 22 G/C marker (rs362691) in cases as compared to controls. Pair-wise linkage disequilibrium analysis demonstrated two separate LD blocks with moderately high D′ values in epileptic cases. Based on these data, we have carried out haplotype case–control analysis. Even though we found over-representation of A-C haplotype of intron 12 A/C/exon 22 G/C markers and haplotype combination involving G-allele of exon 22 marker in cases and controls, respectively, the overall test was not significant. LD in this region involving this marker was also more robust in epileptic cases. Taken together, the results provide possible evidences for association of exon 22 G/C marker or any marker in the vicinity, which is in LD with this marker with epilepsy in the West Bengal population. Further investigations involving higher sample sizes are warranted to validate the present finding.     

Adhesion Pattern and Prognosis Studies of T4N0M0 Colorectal Cancer Following En Bloc Multivisceral Resection: Evaluation of T4 Subclassification

In current TNM stage system, T4 lesions represent a complex group and should be considered to further optimize the classification. This study evaluates the significance of adhesion pattern in T4 subclassification based on prognostic analysis of T4N0M0 colorectal cancer following en bloc multivisceral resection (MVR). Prospectively collected data (1992–2004) were analyzed for 278 patients with stage T4N0M0 lesions following MVR for colorectal cancer. Patients were divided into inflammatory adhesion (IA) and malignant invasion (MI) groups based on adhesion to adjacent organs. Survival was evaluated by Kaplan–Meier and Cox proportional hazards regression analyses. MI was detected in 249 of 460 (54.1%) resected organs and in 159 of 287 (55.40%) patients undergoing MVR. Compared with IA group, patients in MI group showed no significant difference in clinicopathological data except tumor differentiation (P = 0.0376). Cox proportional hazards regression showed that MI was independently associated with overall survival among both colon (HR = 2.028; P = 0.0001) and rectal (HR = 0.451; P = 0.0002) cancer patients. Kaplan–Meier analysis showed that MI patients had a significantly higher MVR compared with IA patients (colon cancer: P = 0.0018; rectal cancer: P = 0.0116). In conclusion, MI was validated as an adverse prognostic factor for stage T4N0M0 colorectal cancer following MVR suggesting that it may be classified as a T4-subgroup in order to reinforce practice guidelines.     

Adhesion to the hydrocarbon phase increases phenanthrene degradation by <Emphasis Type="Italic">Pseudomonas fluorescens</Emphasis> LP6a

Microbial adhesion is an important factor that can influence biodegradation of poorly water soluble hydrocarbons such as phenanthrene. This study examined how adhesion to an oil–water interface, as mediated by 1-dodecanol, enhanced phenanthrene biodegradation by Pseudomonas fluorescens LP6a. Phenanthrene was dissolved in heptamethylnonane and added to the aerobic aqueous growth medium to form a two phase mixture. 1-Dodecanol was non-toxic and furthermore could be biodegraded slowly by this strain. The alcohol promoted adhesion of the bacterial cells to the oil–water interface without significantly changing the interfacial or surface tension. Introducing 1-dodecanol at concentrations from 217 to 4,100 mg l⁻¹ increased phenanthrene biodegradation by about 30% after 120 h incubation. After 100 h incubation, cultures initially containing 120 or 160 mg l⁻¹ 1-dodecanol had mineralized >10% of the phenanthrene whereas those incubated without 1-dodecanol had mineralized only 4.5%. The production and accumulation of putative phenanthrene metabolites in the aqueous phase of cultures likewise increased in response to the addition of 1-dodecanol. The results suggest that enhanced adhesion of bacterial cells to the oil–water interface was the main factor responsible for enhanced biodegradation of phenanthrene to presumed polar metabolites and to CO₂.     

Effect of Ganciclovir on murine cytomegalovirus-induced hearing loss in a mouse model

We evaluated the effect of Ganciclovir on murine cytomegalovirus (MCMV)-induced hearing impairment in a mouse model by studying modulations in auditory brainstem response (ABR) and pathological changes in the inner ear. MCMV infection was established via trans-brain. For this purpose, 24 BALB/c newborn mice were randomly and equally divided into control group (10 μl of sterile normal saline was injected); model group (10 μl of MCMV TCID50—10⁴ IU/0.1 ml was injected); and interfered group (Trans-brain MCMV; Ganciclovir at the rate of 60 mg/kg was intraperitoneally injected). ABR audiometry was performed after 14 days. Acoustic vesicles were obtained for MCMV-PCR analysis and histopathological examination. Comparing ABR in model group against controls, incubation period of wave was lengthened (F = 9.151, P = 0.011–0.05) and wave amplitude was cut down (F = 5.095, P = 0.043–0.05). Comparing ABR in model group against interfered group, incubation period and amplitude of wave were F = 13.797 (P = 0.003–0.05) and F = 14.587 (P = 0.002–0.05), respectively. Cochlear histopathological changes in model group included thickening of vestibular membrane, lymphocytic infiltration, and fibrous degeneration of cochlear duct. In Ganciclovir interfered group, however, these pathologic changes were less significant as compared with those of model group. We, therefore, conclude that Ganciclovir treatment at the early stage of MCMV-induced hearing impairment inhibits the disease progression in infected mice.     

Protection of Selenium on Hepatic Mitochondrial Respiratory Control Ratio and Respiratory Chain Complex Activities in Ducklings Intoxicated with Aflatoxin B<Subscript>1</Subscript>

To investigate the protection of selenium on hepatic mitochondrial functions, 90 7-day-old ducklings were randomly divided into three groups (groups I–III). Group I was used as a blank control. Group II was administered with aflatoxin B₁ (0.1 mg/kg body weight). Group III was administered with aflatoxin B₁ (0.1 mg/kg body weight) plus selenium (sodium selenite, 1 mg/kg body weight). All treatments were given once daily for 21 days. The results showed that the activities of hepatic mitochondrial complexes I–IV in group II ducklings significantly decreased when compared with group I (P < 0.01). Furthermore, the activities of hepatic mitochondrial complexes I–IV in group III significantly increased when compared with group II (P < 0.05). The hepatic mitochondrial respiratory control ratio (RCR) in group II ducklings significantly decreased when compared with group I (P < 0.01). In addition, the hepatic mitochondrial RCR in group III significantly increased when compared with group II (P < 0.05). These results revealed that the aflatoxin B₁ significantly induced hepatic mitochondrial dysfunction in the activities of hepatic mitochondrial respiratory chain complexes I–IV and the RCR in ducklings. However, sodium selenite could significantly ameliorate the negative effect induced by aflatoxin B₁.