Effect of vinpocetine on retrograde axoplasmic transport

Vinpocetine, a derivate of vincamine, is widely used in the clinical pharmacotherapy of cerebral circulatory diseases. Herewith we report on a novel effect of vinpocetine: inhibition of retrograde axoplasmic transport of nerve growth factor (NGF) in the peripheral nerve. Blockade of retrograde transport of NGF results in transganglionic degenerative atrophy (TDA) in the segmentally related ipsilateral superficial spinal dorsal horn, which is characterized by depletion of the marker enzymes fluoride-resistant acid phosphatase (FRAP) and thiamine monophosphatase (TMP). At the same time, pain-related neuropeptides such as substance P (SP) and calcitonin gene-related peptide (CGRP), are depleted from lamina I-III from the segmentally related, ipsitateral Rolando substance of the spinal cord. On the basis of these experiments it is suggested that vinpocetine may result in a locally restricted decrease of nociception, that might be useful in clinical treatment of intractable pain. Pilot self-experiments support this assumption.     

Activation of the primary motor cortex by somatosensory stimulation in adult rats is mediated mainly by associational connections from the somatosensory cortex

In anaesthetized adult rats, facial nerve injury causes a disinhibition of the interhemispheric connections between homotopic representation fields in the primary motor cortex with a latency of 4 min (Toldi et al., 1996, Neurosci Lett. 203, 179-182). One possible explanation for the induction of such rapid changes is an alteration of the somatosensory input to the motor cortex. To test this hypothesis, unit activity in primary motor cortex was recorded during electrical stimulation of trigeminal afferents in the contralateral whisker-pad. About one-third of all recorded primary motor cortex neurons responded with latencies shorter than in the ventrolateral and posterior nuclei of the thalamus. Responses failed at stimulation frequencies > or = 10 Hz and after elimination or inactivation of the somatosensory cortex. Within primary motor cortex, the activatable neurons displayed a bilaminar distribution and were identified as pyramidal neurons by neurobiotin labelling. The results suggest that trigeminal afferents participate in modulation of the activity of primary motor cortex output neurons via primary somatosensory cortex-to-primary motor cortex associational connections, even under anaesthesia.     

Reference data for ultrasound bone characteristics in Hungarian children aged 7–19 years

Backround: Osteoporosis is a common disease and physical activity (PA) has a favourable influence on bone status.

Aim: To establish normative data for calcaneal quantitative ultrasound (QUS) bone characteristics in children and to analyse the relationships between PA, anthropometric and bone parameters.

Subjects and methods: Hungarian children aged 7–19 (n?=?2674; 1325 girls, 1349 boys) provided PA, anthropometric and bone data. QUS parameters were registered with Sonost3000 densitometer (speed of sound: SOS, m/s; broadband ultrasound attenuation: BUA, dB/MHz; bone quantity index (BQI?=?αSOS?+?βBUA). Reference centiles of QUS parameters were constructed by LMS method. Multivariate linear regression models were used to analyse the relationships.

Results: QUS bone parameters increased with age. There were no gender differences, except in 11- and 19-year-old children, where boys showed higher values. SOS (1497.15?±?15.72 vs 1494.05?±?14.81?m/s) and BQI (65.31?±?16.71 vs 62.26?±?15.78) were higher in athletic children. The regression model revealed significant relations between SOS and age, relative muscle mass and PA; BUA correlated with gender, morphological age, BMI, relative muscle mass and PA.

Conclusions: Changes in the bone parameters among 7–19-year-old Hungarian children depended on age, anthropometric dimensions and the level of PA. The normative data could be used for monitoring QUS bone parameters in children, leading to more effective interventions for healthy bones.     

β-Cell neogenesis: experimental considerations in adult stem cell differentiation

The contribution of stem cells derived from adult tissues to the recovery of pancreatic islets from chemical injury is controversial. Analysis of nonhematopoietic differentiation of bone marrow-derived cells has yielded positive and negative results under different experimental conditions. Using the smallest subset of bone marrow cells lacking immuno-hematopoietic lineage markers, we have detected incorporation and conversion into insulin-producing cells. Donor cells identified by genomic markers silence green fluorescent protein (GFP) expression as a feature of differentiation, in parallel to expressing PDX-1 and proinsulin. Here we elaborate potential experimental difficulties that might result in false-negative results. The use of GFP as a reporter protein is suboptimal for differentiation experiments: (a) the bone marrow of GFP donors partially expresses the reporter protein, (b) differentiating bone marrow cells silence GFP expression, and (c) the endocrine pancreas is constitutively negative for GFP. In addition, design of the experiments, data analysis, and interpretation encounter numerous objective and subjective difficulties. Rigorous evaluation under optimized experimental conditions confirms the capacity of adult bone marrow-derived stem cells to adopt endocrine developmental traits, and demonstrates that GFP downregulation and silencing is a feature of differentiation.     

Dynamic changes in the trends in incidence of type 1 diabetes in children in Hungary (1978-98)

Abstract: Objective: To determine the recent trends in incidence, to analyze the age and geographic distribution, as well as the seasonal pattern of type 1 diabetes in Hungarian children aged 0–14 yr for the period from 1978 to 1998. Methods: Primary ascertainment of cases was by retrospective (1978–88) and by prospective (1989–98) registration using hospital notifications. The level of ascertainment was estimated by the capture–recapture method. The temporal trend was estimated by fitting Poisson regression models to the yearly incidence data. Roger's test was used to investigate possible seasonal variation in time of diagnosis. Heterogeneity between geographic areas was assessed by Poisson regression. Results: A total of 2616 patients (1214 in the first 11 yr, 1402 in the remaining 10 yr) were identified; the male:female ratio was 0.93. The overall standardized incidence rate was 7.87 (95% CI = 7.57–8.18) per 100 000 person‐yr, the lowest in the youngest (0–4 yr) and highest in the oldest (10–14 yr) age group. There was an increasing trend in incidence with a largest relative annual increase in the youngest age group. Seasonal and regional variations in incidence were also observed. Conclusion: Our 21‐yr study shows dynamic changes in incidence of childhood type 1 diabetes in Hungary, probably reflecting changes in the environment.     

Systemic lupus erythematosus: all roads lead to type I interferons

In recent years, the study of systemic lupus erythematosus (SLE) patients has revealed a central role for type I interferon (IFN) in disease pathogenesis. IFN induces the unabated activation of peripheral dendritic cells, which select and activate autoreactive T cells rather than deleting them, thus failing to induce peripheral tolerance. IFN also directly affects T cells and B cells. Furthermore, immune complexes binding to FcgammaR and Toll-like receptors provide an amplification loop for IFN production and B-cell activation in SLE. Polymorphisms in genes that control IFN production or its downstream signaling pathway, such as IRF5, might be responsible for some of these alterations. This novel information is leading to the development of IFN antagonists as a potential therapeutic intervention in SLE, thus bringing hope to SLE patients.     

Isolation and complete genome characterization of novel reassortant orthoreovirus from common vole (<Emphasis Type="Italic">Microtus arvalis</Emphasis>)

A novel mammalian orthoreovirus (MRV) strain was isolated from the lung tissue of a common vole (Microtus arvalis) with Tula hantavirus infection. Seven segments (L1–L3, M2–M3, S2, and S4) of the Hungarian MRV isolate MORV/47Ma/06 revealed a high similarity with an MRV strain detected in bank vole (Myodes glareolus) in Germany. The M1 and S3 segment of the Hungarian isolate showed the closest relationship with the sequence of a Slovenian human and a French murine isolate, respectively. The highest nucleotide and amino acid identity values were above 90 and 95% in all of the comparisons to the reference sequences in GenBank, except for the S1 with a maximum of 69.6% nucleotide and 75.4% amino acid identity. As wild rodents are among the main sources of zoonotic infections, the reservoir role of these animals and zoonotic potential of rodent origin MRVs need to be further investigated.