Severe dystonic encephalopathy without hyperphenylalaninemia associated with an 18‐bp deletion within the proximal GCH1 promoter

In a recent GCH1 mutation screen, an 18‐bp deletion was identified within the proximal promoter in two patients with early‐onset Parkinson's disease. The mutation removes cAMP response element critical for adequate GTP cyclohydrolase I activity in selected cell types, including dopaminergic neurons, but its biological significance was unclear as it was also detected in one control individual. We present an 11‐year‐old boy with infantile‐onset severe dystonic encephalopathy without hyperphenylalaninemia whom we found compound heterozygous for the same promoter GCH1 deletion and another common missense mutation associated with classical dopa‐responsive dystonia. Extensive diagnostic work up excluded other causes of dystonia, and comprehensive mutation scan did not reveal any additional GCH1 sequence variations, supporting the association between the promoter deletion and disease phenotype. © 2010 Movement Disorder Society     

Ureteral damage during appendicectomy

A case of right ureteric damage in a 7-year-old boy who underwent appendicectomy is described. Ultrasound, magnetic resonance urography, nephrostogram, and retrograde ureterogram were helpful in defining the nature and extent of the lesion. He underwent staged procedures of percutaneous nephrostomy, elective resection and reconstruction of midureteral segment, and subsequent removal of double J stent and made a smooth recovery.Ureteric injuries, although rare, have serious consequences. A high index of suspicion is essential for diagnosis. Management is influenced by site, type, extent, and mechanism of injury, as well as the timing of detection.     

PLP1 gene duplication as a cause of the classic form of Pelizaeus-Merzbacher disease - case report

Pelizaeus-Merzbacher disease (PMD) is a rare X-linked dysmyelination disorder of the central nervous system (CNS). PMD is caused by mutations in the PLP1 gene located at Xq22 and encoding the major myelin component in CNS, proteolipid protein 1 (PLP1). The disease is clinically heterogeneous. Phenotypes are generally categorized into classic and connatal forms. Connatal PMD has more rapid progression with early death, while patients with classic PMD generally survive to adulthood. Both forms of the disease are caused by point mutations as well as rearrangements - multiplication (mainly duplication) and deletion of the PLP1 gene. We present a case of a male patient affected by the classic form of PMD with benign course, except severe dysarthria with the characteristic laryngeal stridor, which is more typical for connatal form of the disease. The diagnosis has been confirmed at the molecular level. The patient has duplication of all 7 exons of the PLP1 gene. This duplication was inherited from the patient's mother, who is an unaffected carrier of the mutation. The patient's family pedigree analysis revealed the interfamilial variability of the phenotype among affected male relatives.     

Evaluation of postural balance control in patients with multiple sclerosis – effect of different sensory conditions and arithmetic task execution. A pilot study

Background and purposeThe purpose of this study was to investigate the effect of concomitant cognitive task execution and different sensory conditions on balance control in patients with multiple sclerosis (MS).Material and methodsThirty-two subjects with MS and 30 healthy age- and sex-matched control subjects were included in the study. Balance Performance Oriented Mobility Assessment was performed in all subjects. Their spontaneous sway characteristics while standing with different sensory conditions and during execution of a simple arithmetic task were analysed. Mean sway in the coronary and sagittal plane, as well as sway velocity, were measured.ResultsThe values of all evaluated variables obtained in all tests were significantly higher in the MS group than in controls. In the MS group, more pronounced progression of changes in response to increased difficulty of the test was also observed. Analysis of risk of falls in MS revealed a significant increase of sway velocity and mean sway in the mediolateral and anteroposterior plane in the majority of tests.ConclusionsPostural stability in patients with MS is significantly decreased in comparison with the control group in all evaluated conditions. Stability deficit is enhanced in response to more difficult conditions of evaluation. Increased risk of falls is related to the increased postural sway velocity and length of mean sway; this association is most pronounced in the coronary plane.     

Inhibition of vesicular stomatitis virus replication in the course of HIV infection in patients with different stages of immunodeficiency

The replication of vesicular stomatitis virus (VSV) in isolated human leukocytes has been used to measure the level of nonspecific antiviral immunity. However, during infection with some pathogens, the main effect observed is caused by interaction between the pathogen and VSV. This was also noted in advanced stages of HIV infection, when an inverse association between HIV viral load and VSV replication was found. The mutual effect was markedly stronger than the correlation between the VSV replication level and CD4(+) T-cell count. Since successful antiretroviral therapy is associated with a decrease in HIV viremia to undetectable levels, the effect of such therapy on VSV replication was expected and confirmed in this investigation. In fact, increased VSV titers were observed together with decreased HIV viral load, particularly in the case of efficient therapeutic schemes, for example those including lopinavir/ritonavir. The results showed that VSV replication capacity reflected the progression of HIV infection. Moreover, the presence of interferon in the plasma of AIDS patients was found to be only partially responsible for the inhibition of VSV replication. The results suggest a specific HIV-VSV interaction, whether direct or indirect. Thus the VSV replication assay may be applied in evaluating the stage of HIV infection.     

Antioxidant potential, paraoxonase 1, ceruloplasmin activity and C-reactive protein concentration in diabetic retinopathy

The aim of this study was to evaluate the ferric-reducing ability of serum (FRAS), paraoxonase 1 (PON1), ceruloplasmin serum oxidase activity and hsCRP level in patients with type1 diabetes mellitus without and with diabetic retinopathy. The study was performed in 76 patients with type 1 diabetes mellitus, 35 without diabetic retinopathy (group 1) and 41 with preproliferative and proliferative retinopathy (group 2). Control group consisted of 35 nondiabetic, age-, gender-, body mass-matched healthy volunteers who came to the outpatient clinic for a routine health check-up. We evaluated FRAS using the method described by Benzie and Strain; PON1 by kinetic spectrophotometric assay with paraoxon as substrate and ceruloplasmin using its oxidative activity with 3-phenylenodiamine as substrate. CRP was measured with a high sensitive enzyme immunoassay. PON1 activity was significantly decreased in patients with diabetic retinopathy (227.66 ± 123.57 U/l) when compared with control (312.04 ± 129.77 U/l). FRAS was significantly decreased in group 2 (439.33 ± 79.87 μmol/l) when compared with group 1 (522.79 ± 167.56 μmol/l) and control (529.80 ± 81.99 μmol/l). Ceruloplasmin activity was significantly elevated in group 1 (58.36 ± 22.56 U/g protein) when compared with control (45.22 ± 14.96 U/g protein). We have found significant increase in hsCRP level in group 2 (3.71 ± 2.47 mg/l) when compared with group 1 (1.75 ± 1.01 mg/l) and control (0.57 ± 0.46 mg/l). The PON1/CRP ratio in control group was significantly increased when compared with diabetic patients and was significantly decreased in group 2 compared with group 1. We have not found gender-dependent difference in studied parameters in both control and in study groups. We have found tendency to decrease the serum activity of FRAS and hsCRP in elder patients but the difference was significant only in group 2. FRAS and PON 1 activity is decreased in patients with type 1 diabetes mellitus with presence of diabetic retinopathy which confirms that oxidative stress could play a role in pathogenesis of diabetic retinopathy. Significantly elevated levels of hsCRP in diabetic patients with the presence of diabetic retinopathy compared with patients without diabetic retinopathy providing a link between inflammation and the development of microvascular complication of diabetes. Because of the significant difference in PON1/CRP ratio between patients without and with the presence of diabetic retinopathy, it seems that PON1:CRP ratio may be used as a biochemical marker for progression of retinopathy. The link between the antioxidant concentration, inflammation and the development of diabetes complications needs further longitudinal studies in order to confirm our findings.     

Extract from Aronia melanocarpa fruits potentiates the inhibition of platelet aggregation in the presence of endothelial cells

Introduction

Some polyphenolic compounds extracted from Aronia melanocarpa fruits (AM) have been reported to be cardioprotective agents. In this study we evaluated the ability of AM extract to increase the efficacy of human umbilical vein endothelial cells (HUVECs) to inhibit platelet functions in vitro.

Material and methods

This study encompasses two models of monitoring platelet reactivity: optical aggregation and platelet degranulation (monitored as the surface CD62P expression) in PRP upon the stimulation with ADP.

Results

We observed that only at low concentrations (5 µg/ml) did AM extract significantly improve antiplatelet action of HUVECs towards ADP-activated platelets in the aggregation test.

Conclusions

It is concluded that the potentiating effect of AM extract on the endothelial cell-mediated inhibition of platelet aggregation clearly depends on the used concentrations of Aronia-derived active compounds. Therefore, despite these encouraging preliminary outcomes on the beneficial effects of AM extract polyphenols, more profound dose-effect studies should certainly be considered before the implementation of Aronia-originating compounds in antiplatelet therapy and the prevention of cardiovascular diseases.