Survival and mortality of myotonic dystrophy type 1 (Steinert's disease) in the population of Belgrade.

The purpose of this investigation was to determine survival and mortality in patients with myotonic dystrophy type 1 (DM1) in the Belgrade population within the period from 1983 to 2002. Data of a number of diagnosed DM1 patients with their demographic, clinical and genetic characteristics were gathered from hospital records in all neurologic institutions in Belgrade for the period 1983-2002. Death certificates were reviewed to determine the cause of death.

Epidemiology of myotonic dystrophy type 1 (Steinert disease) in Belgrade (Serbia).

The aim of this study was to estimate the incidence and prevalence of myotonic dystrophy type 1 (DM1) in Belgrade during the period 1983-2002. The patients who had DM1 were ascertained through hospital records from all neurological departments in Belgrade during 1983-2002. The molecular genetic analysis was performed in all patents included in the study.

CaV3.2 is the major molecular substrate for redox regulation of T-type Ca2+ channels in the rat and mouse thalamus.

Although T-type Ca(2+) channels in the thalamus play a crucial role in determining neuronal excitability and are involved in sensory processing and pathophysiology of epilepsy, little is known about the molecular mechanisms involved in their regulation. Here, we report that reducing agents, including endogenous sulfur-containing amino acid l-cysteine, selectively enhance native T-type currents in reticular thalamic (nRT) neurons and recombinant Ca(V)3.2 (alpha1H) currents, but not native and recombinant Ca(V)3.

Conformational transitions and redox potential shifts of cytochrome P450 induced by immobilization.

Cytochrome P450 (P450) from Pseudomonas putida was immobilized on Ag electrodes coated with self-assembled monolayers (SAMs) via electrostatic and hydrophobic interactions as well as by covalent cross-linking. The redox and conformational equilibria of the immobilized protein were studied by potential-dependent surface-enhanced resonance Raman spectroscopy. All immobilization conditions lead to the formation of the cytochrome P420 (P420) form of the enzyme.

Dynamic Trees for unsupervised segmentation and matching of image regions.

We present a probabilistic framework--namely, multiscale generative models known as Dynamic Trees (DT)--for unsupervised image segmentation and subsequent matching of segmented regions in a given set of images. Beyond these novel applications of DTs, we propose important additions for this modeling paradigm. First, we introduce a novel DT architecture, where multilayered observable data are incorporated at all scales of the model.

Midpoint potentials of hemes a and a3 in the quinol oxidase from Acidianus ambivalens are inverted.

The aa3 type B oxygen reductase from the thermophilic archaeon Acidianus ambivalens (QO) was immobilized on silver electrodes and studied by potential-dependent surface-enhanced resonance Raman (SERR) spectroscopy. The immobilized enzyme retains the native structure at the level of the heme pockets and exhibits reversible electrochemistry. From the potential dependence of specific spectral marker bands, the midpoint potentials of hemes a and a3 were unambiguously determined for the first time, being 320 +/- 20 mV for the former and 390 +/- 20 mV for the latter.

The endogenous redox agent L-cysteine induces T-type Ca2+ channel-dependent sensitization of a novel subpopulation of rat peripheral nociceptors.

Recent studies have demonstrated a previously unrecognized contribution of T-type Ca2+ channels in peripheral sensory neurons to pain sensation (nociception). However, the cellular mechanisms underlying the functions of these channels in nociception are not known. Here, in both acutely dissociated and intact rat dorsal root ganglion neurons, we characterize a novel subpopulation of capsaicin- and isolectin B4-positive nociceptors that also expresses a high density of T-type Ca2+ currents.

Proximal dystrophin gene deletions and protein alterations in becker muscular dystrophy.

Alterations in production of cytoskeletal protein dystrophin caused by in-frame gene mutations lead to the Becker muscular dystrophy. In this study we analyzed genotype-phenotype correlation in a group of Becker muscular dystrophy patients with deletions affecting the proximal part of dystrophin gene, encompassing exons 3-13. Four patients with deletions affecting N terminal dystrophin domain had early onset and faster progression of the disease, while three patients with deletions in the proximal part of dystrophin's rod domain had a more benign disease course.

5alpha-reduced neuroactive steroids alleviate thermal and mechanical hyperalgesia in rats with neuropathic pain.

5alpha-reduced neuroactive steroids with selective modulatory action in vitro on T or combined modulatory action on T and GABA(A) currents present in peripheral sensory neurons have been shown to induce potent peripheral analgesia in vivo in intact animals. Although the role of T and GABA(A) currents in pathophysiology of neuropathic pain (NPP) is not established, it appears that blockade of T currents and/or potentiation of GABA(A) currents could be beneficial in the management of NPP. To study the potential usefulness of 5alpha-reduced neuroactive steroids in alleviating NPP, we selected two newly synthesized steroids-ECN and CDNC24-with a selective blocking effect on T currents and a selective potentiating effect on GABA(A) currents, respectively, and commercial analogs-alphaxalone and 3alpha5alphaP-with the effects on both ion channels.

[Epidemiology of myotonic dystrophy type 1 in the population of central Serbia].

The objective of this epidemiological survey was to estimate the frequency and distribution of Myotonic dystrophy type 1 (MD1) (Steinert's disease) in central Serbia, during the period 1983-2002. The data on the number of diagnosed MD1 patients were obtained using the analysis of hospital records, which were examined in all the relevant neurological institutions in central Serbia in the mentioned period. Incidence rate and prevalence were used for the data analysis.

Different kinetic properties of two T-type Ca2+ currents of rat reticular thalamic neurones and their modulation by enflurane.

Currents arising from T-type Ca2+ channels in nucleus reticularis thalami (nRT) play a critical role in generation of low-amplitude oscillatory bursting involving mutually interconnected cortical and thalamic neurones, and are implicated in the state of arousal and sleep, as well as seizures. Here we show in brain slices from young rats that two kinetically different T-type Ca2+ currents exist in nRT neurones, with a slowly inactivating current expressed only on proximal dendrites, and fast inactivating current predominantly expressed on soma. Nickel was about twofold more potent in blocking fast (IC50 64 microM) than slow current (IC50 107 microM).

New evidence that both T-type calcium channels and GABAA channels are responsible for the potent peripheral analgesic effects of 5alpha-reduced neuroactive steroids.

Neurosteroids are potent blockers of neuronal low-voltage activated (T-type) Ca(2+) channels and potentiators of GABA(A) ligand-gated channels, but their effects in peripheral pain pathways have not been studied previously. To investigate potential analgesic effects and the ion channels involved, we tested the ability of locally injected 5alpha-reduced neurosteroids to modulate peripheral thermal nociception to radiant heat in adult rats in vivo and to modulate GABA(A) and T-type Ca(2+) channels in vitro. The steroid anesthetic alphaxalone (ALPX), the endogenous neurosteroid allopregnanolone (3alpha5alphaP), and a related compound ((3alpha,5alpha,17beta)-3-hydroxyandrostane-17-carbonitrile, (ACN)), induced potent, dose-dependent, enantioselective anti-nociception in vivo and modulation of both T-type Ca(2+) currents and GABA(A)-mediated currents in vitro.

Haplotype analysis of the DM1 locus in the Serbian population.

Objectives: Analysis of the CTG-repeat number and three biallelic markers, Alu(+/-), HinfI(+/-), and TaqI(+/-), in the DMPK gene in healthy and myotonic dystrophy type 1 (DM1) Serbian individuals. Also, the consideration of haplotypes in the light of the proposed models of CTG-repeat evolution and origin of the DM1 mutation.

Materials And Methods: Markers were analyzed by PCR and haplotypes were obtained on 203 unrelated normal chromosomes and 24 unrelated DM1 chromosomes.

Contrasting anesthetic sensitivities of T-type Ca2+ channels of reticular thalamic neurons and recombinant Ca(v)3.3 channels.

Reticular thalamocortical neurons express a slowly inactivating T-type Ca(2+) current that is quite similar to that recorded from recombinant Ca(v)3.3b (alpha1Ib) channels. These neurons also express abundant Ca(v)3.

[Deletions in the dystrophin gene and its phenotype expression].

About 60% of both Duchenne's muscular dystrophy (DMD) and Becker's muscular dystrophy (BMD) is due to deletions of dystrophin gene. For cases with deletion mutations the "reading frame" hypothesis predicts that deletions which result in disruption of the translation reading frame prevent production of stable protein and are associated with DMD. In contrast, intragenic deletions that involve exons encoding an integral number of triplet codons maintain proper reading frame.

5beta-reduced neuroactive steroids are novel voltage-dependent blockers of T-type Ca2+ channels in rat sensory neurons in vitro and potent peripheral analgesics in vivo.

T-type Ca(2+) channels are believed to play an important role in pain perception, and anesthetic steroids such as alphaxalone and allopregnanolone, which have a 5alpha-configuration at the steroid A, B ring fusion, are known to inhibit T-type Ca(2+) channels and cause analgesia in a thermal nociceptive model (Soc Neurosci Abstr 29:657.9, 2003). To define further the structure-activity relationships for steroid analgesia, we synthesized and examined a series of 5beta-reduced steroids for their ability to induce thermal antinociception in rats when injected locally into the peripheral receptive fields of the nociceptors and studied their effects on T-type Ca(2+) channel function in vitro.

Redox modulation of peripheral T-type Ca2+ channels in vivo: alteration of nerve injury-induced thermal hyperalgesia.

We reported recently that redox agents, including the endogenous amino acid L-cysteine, modulate T-type Ca2+ currents in primary sensory neurons in vitro, and alter mechanical and thermal nociception in peripheral nociceptors in vivo in intact animals [Neuron 31 (2001) 75]. Here, we studied the effects of locally applied redox agents (L-cysteine and 5,5'-dithio-bis-(2-nitrobenzoic acid) (DTNB) on thermal hyperalgesia in animals with neuropathic pain due to chronic constrictive injury (CCI) of the sciatic nerve. We found that, following injection into the peripheral receptive fields, the endogenous reducing agent L-cysteine increased thermal hyperalgesia in a dose-dependent manner in rats with CCI of the sciatic nerve as well as in sham-operated rats.

Mechanical and thermal anti-nociception in rats after systemic administration of verapamil.

Voltage-gated Ca(2+) channels expressed in neurons may contribute to nociceptive information processing. However, the role of L-type Ca(2+) channels in pain transmission is not well understood. In this study, we examined the effects of systemically administered verapamil, an antihypertensive agent and L-type Ca(2+) channel blocker, on mechanical and thermal withdrawal thresholds in rats.

The recurrence risk of ischemic stroke in childhood.

Objective: To determine the risk of recurrence of ischemic stroke in children and to evaluate the influence of etiological factors and underlying mechanisms on recurrence rate.

Subjects And Methods: Thirty-six children (21 boys and 15 girls) with clinically and radiographically proven ischemic cerebral infarction were prospectively followed up over a period of 1-9 years (median 5 years 5 months). The median age of onset of stroke was 8.

Potent analgesic effects of anticonvulsants on peripheral thermal nociception in rats.

1. Anticonvulsant agents are commonly used to treat neuropathic pain conditions because of their effects on voltage- and ligand-gated channels in central pain pathways. However, their interaction with ion channels in peripheral pain pathways is poorly understood.

[Clinical course and prognosis in hypoxic-ischemic encephalopathy].

Background: Establishing the value of neurological examination, and additional diagnostic methods (ultrasonography and magnetic resonance imaging of the brain) in the diagnosis and prognosis of hypoxic-ischemic encephalopathy and its treatment, tracking the clinical course, and making the prognosis of neurological development in newborn infants with hypoxic-ischemic encephalopathy.

Methods: The group of 40 term newborn infants with suspected intrauterine asphyxia was examined. All the infants were prospectively followed until the 3rd year of age at the Clinic for Neurology and Psychiatry for Children and Youth in order to estimate their neurological development and to diagnose the occurrence of persistent neurological disorders.

[Duchenne's and Becker's muscular dystrophy: analysis of phenotype-genotype correlation in 28 patients] ].

Duchenne's and Becker's muscular dystrophy (DMD & BMD) is a X linked disease caused by mutations in the dystrophic gene. DMD is the malign form of the disease, which significantly shortens the lifetime of the patient, while BMD has late onset with slow progression. Sixty five percent of DMD and BMD cases are caused by deletion of one or more exons in the dystrophic gene, while duplications cause these diseases in 6 to 7% of the cases.

Mechanical and thermal antinociception in rats following systemic administration of mibefradil, a T-type calcium channel blocker.

Voltage-gated Ca(2+) channels play a crucial role in pain perception. We studied the antinociceptive potential of systemically administered mibefradil, a peripherally acting antihypertensive agent and preferential T-type Ca(2+) channel blocker. Systemic injections of mibefradil, in clinically relevant doses, induced mechanical and thermal antinociception in adult rats without compromising their sensorimotor abilities.

Is the 31 CAG repeat allele of the spinocerebellar ataxia 1 (SCA1) gene locus non-specifically associated with trinucleotide expansion diseases?

A number of human hereditary neuromuscular and neurodegenerative disorders are caused by the expansion of trinucleotide repeats within certain genes. The molecular mechanisms that underlie these expansions are not yet known. We have analyzed six trinucleotide repeat-containing loci [spinocerebellar ataxias (SCA1, SCA3, SCA8), dentatorubral-pallidoluysian atrophy (DRPLA), Huntington chorea (HD) and fragile X syndrome (FRAXA)] in myotonic dystrophy type 1 (DM1) patients (n = 52).

250 CTG repeats in DMPK is a threshold for correlation of expansion size and age at onset of juvenile-adult DM1.

Myotonic dystrophy type 1 (DM1) is associated with an expansion of CTG repeats in the 3'UTR of the DMPK gene. It is accepted, as in other trinucleotide diseases, that the number of the repeats is correlated with age at onset and severity of the disease. However, assessment of genotype-phenotype correlation in DM1 is complicated with the expansion-biased somatic instability of mutant alleles over time and difficulties in precise assessment of the number of repeats by standard Southern blot hybridization.