The frequency and magnitude of price-promoted beverages available for sale in Australian supermarkets.

OBJECTIVE: Price promotions are used to influence purchases and represent an important target for obesity prevention policy. However, no long-term contemporary data on the extent and frequency of supermarket price promotions exists. We aimed to evaluate the frequency, magnitude and weekly variation of beverage price promotions available online at two major Australian supermarket chains over 50 weeks. METHODS: Beverages were categorised into four policy-relevant categories (sugar-sweetened beverages, artificially-sweetened beverages, flavoured milk and 100% juice, milk and water). The proportional contribution of each category to the total number of price proportions, the proportion of price promotions within the available product category, the mean discount, and weekly variation in price promotions were calculated. RESULTS: For Coles and Woolworths respectively, 26% and 30% of all beverages were price promoted in any given week. Sugar-sweetened beverages made up the greatest proportion of all price promotions (Coles: 46%, Woolworths: 49%). Within each product category, the proportion of sugar-sweetened and artificially-sweetened beverages that were price promoted was similar, higher than the other categories and reasonably constant over time. Diet drinks and sugar-sweetened soft drinks were most heavily discounted (by 29-40%). CONCLUSIONS: Beverage price promotions are used extensively in Australian supermarkets, undermining efforts to promote healthy population diets. Implications for public health: Policies restricting price promotions on sugar-sweetened beverages are likely to be an important part of strategies to reduce obesity and improve population nutrition.

Saccharomyces cerevisiae, key role of MIG1 gene in metabolic switching: putative fermentation/oxidation.

Saccharomyces cerevisiae can utilize a wide range of carbon sources; however, in the presence of glucose the use of alternate carbon sources would be repressed. Several genes involved in the metabolic pathways exert these effects. Among them, the zinc finger protein, Mig1 (multicopy inhibitor of GAL gene expression) plays important roles in glucose repression of Saccharomyces cerevisiae. To investigate whether the alleviation of glucose effect would result in a switch to oxidative production pathway, MIG1 were disrupted in a haploid laboratory strain (2805) of S. cerevisiae. The impact of this disruption was studied under fully aerobic conditions when glucose was the sole carbon source. Our results showed that glucose repression was partly alleviated; i.e., ethanol, as a significant fermentation marker, and acetate productions were respectively decreased by 14.13% and 43.71% compared to the wild type. In ΔMIG1 strain, the metabolic shifting on the aerobic pathway and a significant increase in pyruvate and glycerol production suggested it as an optimally productive industrial yeast strain. However, further studies are needed to confirm these findings.

MicroRNA dysregulation following spinal cord contusion: implications for neural plasticity and repair.

Spinal cord injury (SCI) is medically and socioeconomically debilitating. Currently, there is a paucity of effective therapies that promote regeneration at the injury site, and limited understanding of mechanisms that can be utilized to therapeutically manipulate spinal cord plasticity. MicroRNAs (miRNAs) constitute novel targets for therapeutic intervention to promote repair and regeneration. Microarray comparisons of the injury sites of contused and sham rat spinal cords, harvested 4 and 14 days following SCI, showed that 32 miRNAs, including miR124, miR129, and miR1, were significantly down-regulated, whereas SNORD2, a translation-initiation factor, was induced. Additionally, three miRNAs including miR21 were significantly induced, indicating adaptive induction of an anti-apoptotic response in the injured cord. Validation of miRNA expression by qRT-PCR and in situ hybridization assays revealed that the influence of SCI on miRNA expression persists up to 14 days and expands both anteriorly and caudally beyond the lesion site. Specifically, changes in miR129-2 and miR146a expression significantly explained the variability in initial injury severity, suggesting that these specific miRNAs may serve as biomarkers and therapeutic targets for SCI. Moreover, the pattern of miRNA changes coincided spatially and temporally with the appearance of SOX2, nestin, and REST immunoreactivity, suggesting that aberrant expression of these miRNAs may not only reflect the emergence of stem cell niches, but also the reemergence in surviving neurons of a pre-neuronal phenotype. Finally, bioinformatics analysis of validated miRNA-targeted genes indicates that miRNA dysregulation may explain apoptosis susceptibility and aberrant cell cycle associated with a loss of neuronal identity, which underlies the pathogenesis of secondary SCI.

Vitrification of the inner perivitelline layer of chicken eggs for use in the sperm-egg interaction assay.

The sperm-egg interaction assay is a good predictor of the fertilizing potential of rooster semen; the ability of chicken sperm to interact with the egg can be assessed by counting the number of holes in the inner perivitelline layer (IPVL) of a freshly laid egg. Although isolated IPVL can be stored for up to 24h, preservation of IPVL for prolonged intervals in liquid nitrogen would facilitate the sperm-egg interaction assay. The objective of this study was to adapt the technique of vitrifying swine oocytes for use with the IPVL. Our hypothesis was that vitrification would not alter the ability of the membrane to bind sperm; therefore, there would be no difference between vitrified and fresh IVPL in the number of hydrolysis holes made by sperm. Our hypothesis was supported; there were no differences in the mean+/-SEM number of holes made by the same sample of sperm in vitrified and in fresh membranes (146.0+/-17.7 holes/mm(2) IPVL and 159.5+/-17.7 holes/mm(2) IPVL, respectively, P>0.05; n=123 IVPLs tested). Furthermore, 80% of frozen-thawed membranes were recovered intact. Because vitrification did not significantly change the ability of membranes to bind sperm, vitrified membranes can be safely used for the sperm-egg interaction assay. Vitrified IVPL would ensure availability for sperm evaluation and facilitate wide distribution of IPVL, enabling assays to be conducted even in the absence of facilities or expertise to prepare membranes.

Wrist and palm indexes in carpal tunnel syndrome.

According to median sensory latency >/= 3.7 ms (wrist-index finger [WIF], 14 cm), median/ulnar sensory latency difference to ring finger >/= 0.5 ms (14 cm) or median midpalm (8 cm) latency >/= 2.3 ms (all peak-measured), 141 Brazilian symptomatic patients (238 hands) have CTS confirmation. Wrist ratio (depth divided by width, WR) and a new wrist/palm ratio (wrist depth divided by the distance between distal wrist crease to the third digit metacarpophalangeal crease, WPR) were measured in all cases. Previous surgery/peripheral neuropathy were excluded; mean age 50.3 years; 90.8% female. Control subjects (486 hands) have mean age 43.0 years; 96.7% female. The mean WR in controls was 0.694 against 0.699, 0.703, 0.707 and 0.721 in CTS groups of progressive WIF severity. The mean WPR in controls was 0.374 against 0.376, 0.382, 0.387 and 0.403 in CTS groups of WIF progressive severity. Both were statistically significant for the last two groups (WIF > 4.4 ms, moderate, and, WIF unrecordable, severe). BMI increases togetherwith CTS severity and WR. It was concluded that both WR/WPR have a progressive correlation with the severity of CTS but with statistically significance only in groups moderate and severe. In these groups both WR and BMI have progressive increase and we believe that the latter could be a risk factor as important as important WR/WPR.

Body mass index and carpal tunnel syndrome.

Carpal tunnel syndrome (CTS) has been correlated to body mass index (BMI) increase. The present study was done in a Brazilian population to compare BMI values in the following groups: first, CTS vs. controls subjects, and, second CTS groups of increasing median sensory latency (MSL). According to MSL>/=3.7 ms (wrist-index finger, 14 cm), median/ulnar sensory latency difference>/=0.5 ms (ring finger, 14 cm) or median palm-to-wrist (8 cm) latency>/=2.3 ms (all peak-measured), 141 cases (238 hands) had CTS confirmation. All were symptomatic; previous surgery and polyneuropathy were excluded; mean age 50.3; 90.8% female. Controls subjects (n=243; mean age 43.0; 96. 7% female) and CTS cases had BMI calculated (kg/m2). Controls subjects had a mean BMI of 25.43+/-4.80 versus 28.38+/-4.69 of all CTS cases, a statistically significant difference (p < 0.001). The CTS groups of increasing MSL severity do not show additional increase in BMI (28.44 for incipient, 28.27 for mild, 28.75 for moderate and 29.0 for severe). We conclude that CTS cases have a significant correlation with higher BMI when compared to controls subjects; however, higher BMI do not represent a statistically significant increasing risk for more severe MSL.

Theiler's murine encephalomyelitis virus induces rapid necrosis and delayed apoptosis in myelinated mouse cerebellar explant cultures.

Infection with the Daniel strain of Theiler's murine encephalomyelitis (TMEV-DA) virus induces persistent demyelinating lesions in mice and serves as a model for multiple sclerosis. During the acute phase of the disease, however, viral infection leads to cell death in vivo. Viral-induced death may result directly from viral infection of neural cells, or indirectly, by activation of the immune system. To examine the direct effects of TMEV infection on neural cells, myelinated explant cultures of the murine cerebellum were infected with 10(5) pfu of TMEV-DA for periods ranging from 1 to 72 h. Our results indicate that TMEV-DA replicates in cultured neural tissue. Initially, viral antigen is localized to a few isolated neural cells. However, within 72 h antigen was observed in multiple foci that included damaged cells and extracellular debris. Viral infection led to a rapid and cyclical induction of necrosis with a time period that was consistent with the lytic phase of the viral life-cycle. Simultaneously, we observed an increase in apoptosis 48 h post-infection. Electron micrographic analysis indicated that viral-infected cultures contained cells with fragmented nuclei and condensed cytoplasm, characteristic of apoptosis. The localization of apoptosis to the cerebellar granule cell layer, identified these cells as presumptive granule neurons. Viral infection, however, did not lead to myelin damage, though damaged axons were visible in TMEV-infected cultures. These results suggest that during the acute phase of infection, TMEV targets neural cells for apoptosis without directly disrupting myelin. Myelin damage may therefore result from the activation of the immune system.

Ethanol induces Fas/Apo [apoptosis]-1 mRNA and cell suicide in the developing cerebral cortex.

INTRODUCTION: Animal studies modeling fetal alcohol syndrome have demonstrated that developmental exposure to alcohol is associated with decreased brain weight and significant neuronal loss in multiple regions of the developing brain. Our previous data suggest that the Fas/Apo [apoptosis]-1 receptor is transiently expressed in the developing cerebral cortex during the peak period of naturally occurring apoptotic cell death and maximum sensitivity to alcohol. Therefore, we hypothesized that ethanol increases the expression of suicide receptors such as Fas/Apo-1 in the developing fetal cerebral cortex and leads to an upregulation or extension of the normal period of apoptosis and consequent disorganization of the neural circuitry. METHODS: Ethanol was administered in one of four doses (120, 320, 630, and 950 mg/dl) to organotypic explant cultures of the developing cerebral cortex established from postnatal day 2 rats and maintained for 6 days in vitro. The number of cells expressing Fas/Apo-1 receptor mRNA was counted. Apoptosis was measured by the use of two independent assays; a cell death enzyme-linked immunosorbent assay for DNA fragmentation and flow cytometric analysis of Annexin-V binding to phosphatidylserine externalized to the outer leaflet of the plasma membrane. Necrosis was also estimated by two independent measures, the amount of lactate dehydrogenase released into culture medium and flow cytometric analysis of cells that were positive for both Annexin-V and propidium iodide. RESULTS: A significantly larger number of developing cortical cells expressed Fas/Apo-1 mRNA at the lower doses (120 and 320 mg/dl) than at the higher doses (630 and 950 mg/dl). Furthermore, ethanol induced apoptosis in a dose-related manner, with peak apoptosis observed at a dose of 630 mg/dl in the case of DNA fragmentation and at 630 and 950 mg/dl in the case of phosphatidylserine translocation to the outer leaflet of the plasma membrane. Ethanol did not induce necrosis at any of the administered doses of ethanol. CONCLUSIONS: Our data suggest that ethanol induces a susceptibility to apoptotic signals at low doses by upregulating the expression of mRNAs for cytotoxic receptors such as Fas/Apo-1 in the developing cerebral cortex. However, ethanol itself specifically induces apoptosis in the developing cerebral cortex only at higher doses.

Ribonucleotide reductase subunit R1: a gene conferring sensitivity to valproic acid-induced neural tube defects in mice.

Neural tube defects (NTDs), although prevalent and easily diagnosed, are etiologically heterogeneous, rendering mechanistic interpretation problematic. To date, there is evidence that mammalian neural tube closure (NTC) initiates and fuses intermittently at four discrete locations. Disruption of this process at any of these four sites may lead to a region-specific NTDs, possibly arising through closure site-specific genetic mechanisms. Although recent efforts have focused on elucidating the genetic components of NTDs, a void persists regarding gene identification in closure site-specific neural tissue. To this end, experiments were conducted to identify neural tube closure site-specific genes that might confer regional sensitivity to teratogen-induced NTDs. Using an inbred mouse strain (SWV/Fnn) with a high susceptibility to VPA- induced NTDs that specifically targets and disrupts NTC between the prosencephalon and mesencephalon region (future fore/midbrain; neural tube closure site II), we identified a VPA-sensitive closure site II-specific clone. Sequencing of this clone from an SWV neural tube cDNA library confirmed that it encodes the r1 subunit of the cell cycle enzyme ribonucleotide reductase (RNR). The abundance of rnr-r1 mRNA was significantly increased in response to VPA drug treatment. This upregulated expression was accompanied by a significant decrease in cellular proliferation in the closure site II neural tube region of the embryos, as determined by ELISA cellular proliferation assays performed on BrdU-pulsed neuroepithelial cells in vivo. We hypothesize that rnr-r1 plays a critical role in the development of VPA-induced exencephaly.

Glial-derived neurotrophic factor (GDNF) prevents ethanol-induced apoptosis and JUN kinase phosphorylation.

Ethanol exposure during neural development leads to substantial neuronal loss in multiple brain regions. Our previous research indicated that exogenous glial-derived neurotrophic factor (GDNF) attenuated ethanol-induced cerebellar Purkinje cell loss. Additionally, ethanol decreased GDNF release suggesting that ethanol disrupts GDNF-signaling pathways. The present experiments utilized a homogeneous GDNF-responsive neuroblastoma cell line (SK-N-SH) to test the hypothesis that exogenous GDNF could attenuate ethanol-induced cell loss by suppressing cytotoxic signaling pathways and cell suicide. We measured two independently regulated markers of apoptosis, DNA fragmentation and the externalization of phosphatidylserine to the outer cell membrane leaflet. Ethanol induced a dose-related increase in both apoptosis and necrosis. Lower concentrations of ethanol (34 and 68 mM) specifically increased DNA fragmentation, while all concentrations (up to 137 mM) increased phosphatidylserine translocation, suggesting that ethanol induction of apoptosis is not a unitary process. Furthermore, only higher concentrations of ethanol (103 and 137 mM) induced necrosis. Additionally, ethanol specifically induced phosphorylation of c-jun N-terminal-kinase (JNK), a mitogen-activated protein (MAP) kinase selectively associated with apoptosis. In contrast, ethanol did not alter the phosphorylation of another MAP kinase, the extracellular signal-regulated kinases (ERK) that mediate cell survival. Thus, ethanol activated specific intracellular cell death-associated pathways and induced cell death. GDNF, in turn, prevented both ethanol-induced apoptosis and the activation of the death-associated JNK cascade. Therefore, GDNF may regulate multiple pathways to prevent ethanol-induced cell loss.

Ethanol decreases Glial-Derived Neurotrophic Factor (GDNF) protein release but not mRNA expression and increases GDNF-stimulated Shc phosphorylation in the developing cerebellum.

BACKGROUND: Ethanol exposure during development leads to substantial neuronal loss in multiple regions of the brain. Although differentiating Purkinje cells of the cerebellum are particularly vulnerable to ethanol exposure, the mechanisms underlying ethanol-induced Purkinje cell loss have not been well defined. Our previous research indicated that exogenous Glial-Derived Neurotrophic Factor (GDNF) attenuated ethanol-induced Purkinje cell loss in cerebellar explant cultures, which suggests that ethanol, in turn, may decrease endogenous trophic factor-mediated survival mechanisms. METHODS: The present experiments used an explant culture model of the developing rat cerebellum to test the hypothesis that ethanol decreases endogenous trophic support by limiting the availability of trophic factors, such as GDNF, or by altering the activation of key adapter proteins such as Shc (Src homology domain carboxy-terminal) that couple GDNF binding to multiple intracellular signaling pathways. GDNF mRNA and protein levels were measured by reverse northern blot analysis and sandwich enzyme-linked immunosorbent assay respectively, whereas Shc phosphorylation was measured by immunoprecipitation/western immunoblot analysis. RESULTS: The developing cerebellum expresses both GDNF mRNA and protein in vitro. Ethanol exposure (68, 103, or 137 mM) had no effect on cerebellar levels of GDNF mRNA. However, ethanol (68 and 137 mM) decreased levels of GDNF protein released into culture medium. In addition, ethanol itself had no effect on She phosphorylation. However, in the presence of the highest dose of ethanol (137 mM) GDNF did stimulate Shc phosphorylation. CONCLUSIONS: Together, these results suggest that ethanol decreases GDNF-mediated trophic support of Purkinje cells in the developing cerebellum. However, GDNF in turn activates intracellular signaling pathways throughout the developing cerebellum as part of its Purkinje cell-selective neuroprotective response to ethanol exposure.

Overlapping and divergent actions of estrogen and the neurotrophins on cell fate and p53-dependent signal transduction in conditionally immortalized cerebral cortical neuroblasts.

The developing cerebral cortex undergoes overlapping periods of neurogenesis, suicide, and differentiation to generate the mature cortical plate. The following experiments examined the role of the gonadal hormone estrogen in comparison to the neurotrophins, in the regulation of p53-dependent cortical cell fate. To synchronize choices between neurogenesis, apoptosis, and neural differentiation, embryonic rat cerebral cortical neuroblasts were conditionally immortalized with the SV40 large T antigen containing the tsA58/U19 temperature-sensitive mutations. At the nonpermissive temperature, cessation of large T antigen expression was accompanied by induction of p53, as well as the p53-dependent proteins, wild-type p53-activated fragment-1/Cdk (cyclin-dependent kinase)-interacting protein-1 (p21/Waf1), Bcl (B-cell lymphoma)-associated protein (Bax), and murine double minute 2 (MDM2), that lead to cell cycle-arrest, suicide, and p53 inhibition, respectively. Simultaneously, neuroblasts exit cell cycle and die apoptotically or differentiate primarily into astrocytes and immature postmitotic neuroblasts. At the nonpermissive temperature, estrogen specifically induced an antagonist-independent increase in phosphorylated p53 expression, while increasing p21/Waf1 and decreasing Bax. Coincidentally, estrogen rapidly increased and then decreased MDM2 relative to controls, suggesting temporal modulation of p53 function. Both estrogen and neurotrophins prevented DNA fragmentation, a marker for apoptosis. However, estrogen also induced a transient increase in released lactate dehydrogenase, suggesting that estrogen simultaneously induced rapid cell death in a subpopulation of cells. In contrast to the neurotrophins, estrogen also increased cell proliferation. Both estrogen and the neurotrophins supported neuronal differentiation. However, in contrast to the neurotrophins, estrogen only supported the expression of a subset of oligodendrocytic markers. These results suggest that estrogen and the neurotrophins support overlapping and distinct aspects of differentiation in the developing cerebral cortex.

Fas/Apo [apoptosis]-1 and associated proteins in the differentiating cerebral cortex: induction of caspase-dependent cell death and activation of NF-kappaB.

The developing cerebral cortex undergoes a period of substantial cell death. The present studies examine the role of the suicide receptor Fas/Apo[apoptosis]-1 in cerebral cortical development. Fas mRNA and protein are transiently expressed in subsets of cells within the developing rat cerebral cortex during the peak period of apoptosis. Fas-immunoreactive cells were localized in close proximity to Fas ligand (FasL)-expressing cells. The Fas-associated signaling protein receptor interacting protein (RIP) was expressed by some Fas-expressing cells, whereas Fas-associated death domain (FADD) was undetectable in the early postnatal cerebral cortex. FLICE-inhibitory protein (FLIP), an inhibitor of Fas activation, was also expressed in the postnatal cerebral cortex. Fas expression was more ubiquitous in embryonic cortical neuroblasts in dissociated culture compared to in situ within the developing brain, suggesting that the environmental milieu partly suppresses Fas expression at this developmental stage. Furthermore, FADD, RIP, and FLIP were also expressed by subsets of dissociated cortical neuroblasts in culture. Fas activation by ligand (FasL) or anti-Fas antibody induced caspase-dependent cell death in primary embryonic cortical neuroblast cultures. The activation of Fas was also accompanied by a rapid downregulation of Fas receptor expression, non-cell cycle-related incorporation of nucleic acids and nuclear translocation of the RelA/p65 subunit of the transcription factor NF-kappaB. Together, these data suggest that adult cortical cell number may be established, in part, by an active process of receptor-mediated cell suicide, initiated in situ by killer (FasL-expressing) cells and that Fas may have functions in addition to suicide in the developing brain.

Glial-derived neurotrophic factor rescues calbindin-D28k-immunoreactive neurons in alcohol-treated cerebellar explant cultures.

Ethanol exposure during development leads to alterations in neuronal differentiation and profound neuronal loss in multiple regions of the developing brain. Although differentiating Purkinje cells of the cerebellum are particularly vulnerable to ethanol exposure, the mechanisms that ameliorate ethanol-induced Purkinje cell loss have not been well defined. Previous research indicates that glial-derived neurotrophic factor (GDNF), a member of the transforming growth factor-beta family, promotes the survival of several neuronal populations, including cerebellar Purkinje cells. Therefore, we examined whether GDNF could attenuate ethanol-induced Purkinje cell loss in an in vitro model system using calbindin-D28k immunoreactivity as a specific marker for Purkinje cells. We found that ethanol led to a significant dose-related decline in calbindin-D28k-immunoreactive cells in explant cultures of the developing cerebellum. However, concurrent administration of GDNF led to a significant rescue of calbindin-D28k-immunoreactive cells. Therefore, our results suggest that GDNF prevents ethanol-associated Purkinje cell loss.

Fibrilação atrial no idoso: uma abordagem prática / Atrial fibrillation in the elderly: a practical approach

A incidência da fibrilação atrial aumenta com a idade, bem como as complicaçöes decorrentes dela própria e de seu tratamento, isto é, a anticoagulação. A principal complicação é a embolia cerebral, aumentada no idoso. Infelizamente, a incidência de complicaçöes hemorrágicas graves devido aos anticoagulantes está também aumentada e o ácido acetilsalicílico não se mostrou muito eficaz nessa faixa etária. A disfunção diastólica e as cardiopatias usualmente concomitantes tornam o idoso particularmente sensível às alteraçöes hemodinâmicas impostas pela fibrilação atrial, não sendo raras a dispnéia, as palpitaçöes constantes, a insufuciência cardíaca e as síncopes. Sendo assim, os autores propöem uma ênfase maior na tentativa de restauração e manutenção do ritmo sinusal nessa população, a fim de evitar a ocorrência de embolias sistêmicas sem o risco de hemorragias, além de proporcionar melhora mais eficaz da sintomatologia.

Heart rate variability in myocardial infarction with and without malignant arrhythmias: comparison with heart transplant recipients and normal subjects.

Myocardial autonomic denervation occurs after acute MI. This process is followed by a reduction of heart rate variability (HRV) and an increase of malignant ventricular arrhythmias and sudden death. This study investigated whether there are any significant differences in HRV among the population of MI who did and did not have malignant ventricular arrhythmias (MVAs), normal subjects and heart transplant recipients, the paradigm of the denervated heart. We studied 25 subjects aged 42 +/- 17 years, with normal clinical and cardiac noninvasive evaluation (group A); 70 patients aged 57 +/- 14 years, who had MI but no arrhythmic event in 36 months of follow-up (group B); 13 patients with MI aged 65 +/- 9 years, who had had sustained VT, VF, or sudden death (group C); and 16 cardiac transplant recipients aged 35 +/- 14 years (group D). The ECG was sampled for 256 seconds. We calculated, in time and frequency domain, the standard deviation of the RR cycle length and the spectral component's very low frequency (< 0.05 Hz), low frequency (0.05-0.15 Hz), and high frequency (0.15-0.35 Hz). The values of HRV in group A were significantly greater than in groups B, C, and D (P < 0.001) and greater in group B than in groups C and D (P < 0.001). Groups C and D did not differ (P = 0.610). These data indicate that HRV of patients who have had an MI and MVAs is very similar to that of heart transplant recipients. This is an indirect evidence that myocardial autonomic denervation may play an important role in the genesis of malignant arrhythmic events.

Ablaçäo transcateter por radiofrequência. Tratamento curativo da taquicardia por reentrada nodal

A taquicardia por reentrada nodal (TRN) corresponde, aproximadamente, 50 a 70 por cento dos tipos de taquicardia paroxística supraventricular (TPSV). Existe certa prevalência favorável ao sexo feminino e em menores de 40 anos de idade. A frequência cardíaca (FC), durante o paroxismo taquicárdico, pode oscilar de 100 a 280bpm, com valores médios em torno de 170bpm. A arquitetura complexa do nódulo atrioventricular (NAV), com sua característica de anisotropia tissular e heterogeneidade de conduçäo dompulso elétrico, com dissociaçäo longitudinal, levando ao chamado comportamento dual de conduçäo atrioventricular (AV) ou ventrículo-atrial, predispöes ao microcircuito de reentrada intranodal -base fisiopatológica da TRN. A seguir, as características eletrofisiológicas da estrutura do sistema de conduçäo, desde aspectos eletrofisiológicos até modalidades de abordagem terapêutica, visando o esclarecimento do mecanismo da taquicardia e o procedimento técnico utilizado para sua erradiaçäo.

Identification of a putative estrogen response element in the gene encoding brain-derived neurotrophic factor.

We have been studying the role and mechanism of estrogen action in the survival and differentiation of neurons in the basal forebrain and its targets in the cerebral cortex, hippocampus, and olfactory bulb. Previous work has shown that estrogen-target neurons in these regions widely coexpress the mRNAs for the neurotrophin ligands and their receptors, suggesting a potential substrate for estrogen-neurotrophin interactions. Subsequent work indicated that estrogen regulates the expression of two neurotrophin receptor mRNAs in prototypic peripheral neural targets of nerve growth factor. We report herein that the gene encoding the neurotophin brain-derived neurotrophic factor (BDNF) contains a sequence similar to the canonical estrogen response element found in estrogen-target genes. Gel shift and DNA footprinting assays indicate that estrogen receptor-ligand complexes bind to this sequence in the BDNF gene. In vivo, BDNF mRNA was rapidly up-regulated in the cerebral cortex and the olfactory bulb of ovariectomized animals exposed to estrogen. These data suggest that estrogen may regulate BDNF transcription, supporting our hypothesis that estrogen may be in a position to influence neurotrophin-mediated cell functioning, by increasing the availability of specific neurotrophins in forebrain neurons.

Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. Regulation of expression in response to injury.

The neurotrophins, a family of related polypeptide growth factors including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3 and NT-4/5 promote the survival and differentiation of distinctive sets of embryonic neurons. Here we define a new functional role for neurotrophins, as autocrine or local paracrine mediators of vascular smooth muscle cell migration. We have identified neurotrophins, and their cognate receptors, the trk tyrosine kinases, in human and rat vascular smooth muscle cells in vivo. In vitro, cultured human smooth muscle cells express BDNF; NT-3; and trk A, B, and C. Similarly, rat smooth muscle cells expressed all three trk receptors as well as all four neurotrophins. Moreover, NGF induces cultured human smooth muscle cell migration at subnanomolar concentrations. In the rat aortic balloon deendothelialization model of vascular injury, the expression of NGF, BNDF, and their receptors trk A and trk B increased dramatically in the area of injury within 3 days and persisted during the formation of the neointima. In human coronary atherosclerotic lesions, BDNF, NT-3, and NT-4/5, and the trk B and trk C receptors could be demonstrated in smooth muscle cells. These findings suggest that neurotrophins play an important role in regulating the response of vascular smooth muscle cells to injury.