Post-traumatic unilateral atlanto-axial rotatory subluxation in an adult

This retrospective single-patient case report deals with a rare form of spinal trauma, i.e. atlantoaxial rotatory subluxation. The authors present a review of the literature including a classification of rotatory atlantoaxial subluxation types proposed by Fielding, and describe their own experience with treatment of this condition. A case is reported of a 29-year-old woman with a history of head contusion in a car accident. Immediately after the trauma she had the following symptoms: torticollis and neck pain with decreased cervical motion. Atlantoaxial rotatory subluxation of the right C1-C2 articulation was diagnosed by plain radiographs and CT. The patient was treated surgically by an open reduction, unilateral screw fixation of the right CI-C2 articulation (according to Magerl) and posterior C1-C2 wiring with graft. The normal atlantoaxial relation was restored with disappearance of torticollis. At follow-up certain limitation of neck movements due to C1-C2 stabilization persisted. No complications were noted. The patient remains neurologically intact and has radiographic documentation of fusion.     

The assessment of development of binding antibodies to interferon beta during interferon beta 1a treatment of multiple sclerosis

The importance of binding antibodies (BAb) that develop during the treatment of multiple sclerosis with interferon beta has not been fully explained yet. However, they are generally regarded as one of factors that may diminish treatment efficacy. The aim of the study was to evaluate firstly, BAb occurrence in interferon beta 1-a (IFN beta 1-a)-treated MS patients and secondly, BAb impact on clinical efficacy of this medication. In the 36-month study participants were 21 patients with relapsing-remitting multiple sclerosis, RR-MS, (14 women, 7 men, aged 29.6 +/- 8.5). All the patients were receiving intramuscular IFN beta-1a (Avonex) for 24 months, in the dose of 30 micrograms per week. Clinical parameters and serum BAb levels (the EIA method) were estimated every 3 months. Two control groups, examined only once, included 20 RR-MS patients without IFN-beta therapy and 20 healthy volunteers. While before treatment a high BAb level was found in 2 patients (9.5%), at 6 months of treatment it was found in 8 patients (38.1%). A similar number of patients with high BAb levels was seen throughout the study during the IFN-beta treatment. On therapy completion serum BAb levels decreased very rapidly. After 2 years of treatment, disability as measured by the EDSS scale was more pronounced in patients with serum BAb, but the differences were statistically not significant. No statistically significant relationship was found either between elevated BAb levels and the number of relapses during the IFN-beta treatment (including relapses that required steroid therapy).     

Relationship between oxidative stress and extrinsic coagulation pathway in haemodialyzed patients

Enhanced oxidative stress (SOX), endothelial dysfunction and haemostatic abnormalities are common in end-stage renal failure patients undergoing maintenance haemodialysis (HD). We studied associations among circulating immunoreactive total lipid peroxides as a marker of short-time SOX, autoantibodies against oxidized LDL as a surrogate of prolonged SOX, copper/zinc superoxide dismutase (Cu/Zn SOD) as a major antioxidant enzyme, tissue factor (TF) as a principal initiator of extrinsic coagulation pathway counteracted by its inhibitor (TFPI), and prothrombin fragment 1+2 (F 1+2) as a surrogate of activated haemostasis.

Pre-dialysis blood levels of all the markers studied were higher in 24 clinically stable HD patients compared to 11 healthy controls. Spearman's correlations among the three SOX markers were positive but nonsignificant in both HD patients and controls. In HD subjects, increased Cu/Zn SOD levels directly correlated with those of TF (rho=0.551, p=0.005) and TFPI (rho=0.501, p=0.001); the coagulation markers were also positively associated with each other (rho=0.663, p=0.0004). In healthy subjects, the relations between Cu/Zn SOD, TF and TFPI levels were inverse but not significant, and the direct association between TF and TFPI was nonsignificant either.

In conclusion, increased plasma levels of Cu/Zn SOD, the antioxidant enzyme with emerging endothelial cell-protective and antithrombotic properties, may be a novel part of the system counteracting activated extrinsic coagulation system in maintenance HD patients.     

Catalytic and structural role of the metal ion in dUTP pyrophosphatase

The metal ion dependence of the catalytic activity of recombinant Escherichia coli dUTP pyrophosphatase (dUTPase), an essential enzyme preventing incorporation of uracil into DNA, has been investigated by steady-state kinetic, electron paramagnetic resonance, and electron nuclear double resonance methods. Values of k(cat) and k(cat)K(m) were 4.5 +/- 0.1 s(-1) and 0.49 +/- 0.1 x 10(6) M(-1).s(-1) in the absence of divalent metal ions, 14.7 +/- 2.2 s(-1) and 25.1 +/- 7.4 x 10(6) M(-1).s(-1) in the presence of Mg(2+) or Mn(2+), and 24.2 +/- 3.6 s(-1) and 2.4 +/- 0.7 x 10(6) M(-1).s(-1) when supported by VO(2+) or bis(acetylacetonato)oxovanadium(IV). Binding of VO(2+) to the enzyme in the presence of dUDP, a nonhydrolyzable substrate analog, was specific and competitive with Mg(2+). Electron paramagnetic resonance spectra of the ternary enzyme-VO(2+)-chelate-dUDP complex revealed a pattern of (31)P superhyperfine coupling specifying two structurally equivalent phosphate groups equatorially coordinated to the VO(2+) ion. Proton electron nuclear double resonance spectra revealed an equatorial acetylacetonate ligand, indicating that one of the organic ligands had been displaced. By molecular graphics modeling, we show that the diphosphate group of enzyme-bound dUDP is sterically accessible to a hemi-chelate form of VO(2+). We propose a similar location compatible with all kinetic and spectroscopic results to account for the reactivity of VO(2+) and the VO(2+)-chelate in dUTP hydrolysis. In this location the metal ion could promote an ordered conformation of the C-terminal fragment that is obligatory for catalysis but dynamically flexible in the free enzyme.     

Early detection of renal diseases-urgency or clever choice?

Economical end medical benefits of early referral and nephrological care were presented in patients with very early stages of renal disease.     

Changes in APP,PS1 and other factors related to Alzheimer's disease pathophysiology after trimethyltin-induced brain lesion in the rat

Trimethyltin (TMT) chloride induces limbic system neurodegeneration, resulting in behavioral alterations including cognitive deficits. Different factors related to Alzheimer's disease (AD) were studied after TMT lesion in Sprague-Dawley rats. The expression of amyloid precursor protein (APP) containing 695 amino acids (APP695), APP containing the Kuniz protease inhibitor domain (APP- KPI), presenilin 1 (PS1), c- fos and IL- 1Beta was investigated at different timepoints after a single TMT injection (7 mg/kg i.p.) using in situ hybridization and immunohistochemistry. After the TMT treatment, extensive degeneration of pyramidal neurons was observed in the CA3 region of the hippocampus, concomitant with neurodegeneration in the outer layer of the CA1 region and layer II of entorhinal and piriform cortex. The affected regions showed abundant condensed eosinophilic and TUNEL-positive neuronal cells, that were apparent at day 4 after TMT, increasing to day 7 and subsequently disappearing. In the affected regions the levels of APP695 mRNA gradually declined with time after the TMT injection. While there was no apparent alteration in the overall expression of APP- KPI or PS1 mRNA, detailed analysis of the CA3c region showed that the mRNA expression shifted from neurons to glial cells. Three days after TMT, neurons in the piriform cortex, the CA3 region and DG expressed high levels of c-fos mRNA that slowly declined to become normalized when analyzed at day 28. At day 7 after TMT a few distinct IL- 1Beta mRNA expressing glial cells were observed in the CA3c region. Thus, TMT exposure leads to alterations in the expresson of APP, APP- KPI, PS1, c-fos and IL- 1Beta in the limbic system. These findings suggest that TMT lesions, not only share certain key features of AD symptomatology and regional neurodegeneration, but also induce effects on important factors related to the pathophysiology of AD.     

In vitro antioxidant properties of pentoxifylline, piracetam, and vinpocetine

Oxygen-free radicals play an important role in several physiologic and pathophysiologic processes. In pathologic circumstances, they can modify and damage biologic systems. Because oxygen-free radicals are involved in a wide range of diseases (cerebrovascular, cardiovascular, etc.), scavenging these radicals should be considered as an important therapeutic approach. In our in vitro study, we investigated the antioxidant capacity of three drugs: pentoxiphylline (Sigma Aldrich, St. Louis, MO, USA) piracetam (Sigma Aldrich), and vinpocetine (Richter Gedeon RT, Budapest, Hungary). Phenazine methosulphate was applied to generate free radicals, increasing red blood cell rigidity. Filtration technique and potassium leaking were used to detect the cellular damage and the scavenging effect of the examined drugs. According to our results, at human therapeutic serum concentration, only vinpocetine (Richter Gedeon RT) had significant (p < 0.01) scavenging activity with a protective effect that increased further at higher concentrations. Pentoxiphylline (Sigma Aldrich) and piracetam (Sigma Aldrich) did not have significant antioxidant capacity at therapeutic concentrations, but increasing their concentrations (pentoxiphylline at 100-times, and piracetam at 10-times higher concentrations) led to a significant (p < 0.01) scavenger effect. Our findings suggest that this pronounced antioxidant effect of vinpocetine and even the milder scavenging capacity of pentoxiphylline and piracetam may be of value in the treatment of patients with cerebrovascular disorders, but merits further investigations.     

Effect of 3-nitropropionic acid on kynurenine aminotransferase in the rat brain

Activation of excitatory amino acid receptors by endogenous excitotoxins results in degenerative changes characteristic of neurodegenerative brain diseases such as Huntington's disease. Excitatory amino acid receptors are present in the highest concentration in the striatum, the hippocampal region, and the temporal lobe. The most potent, naturally occurring excitatory amino acid receptor antagonist is kynurenic acid (KYNA) which acts preferentially on N-methyl-D-aspartate (NMDA) receptors. KYNA is produced from L-kynurenine, by the action of the enzymes kynurenine aminotransferases (KAT I and KAT II). Several inhibitors of mitochondrial energy metabolism result in an indirect excitotoxic neuronal degeneration. We examined whether systemic administration of the mitochondrial toxin 3-nitroproprionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase, which also acts by an indirect excitotoxic mechanism, would produce alterations in the immunohistochemical pattern of KAT I. Our present investigations demonstrate that after 15 days of administration of 3-NP, an inhibitor of mitochondrial Complex II, the most severe depletion of KAT I occurred in the striatum; less severe depletion occurred in other brain areas investigated, following a striatum > hippocampus > temporal cortex gradient. The alterations induced by 15 days of 3-NP treatment were less conspicuous in 6-week-old (young) animals than in 3-month-old adults. In these adult animals, 3-NP induced necrotic cores in the striatum, characterized by destruction of neuronal and glial elements, similar to that seen in the histologic and neurochemical features of Huntington's disease. It appears that immunohistochemical depletion of KAT after administration of 3-NP to adult animals may contribute to the pathological processes that characterize Huntington's disease.