Chronic Stress Improves the Myocardial Function without Altering L-type Ca+2 Channel Activity in Rats

Background: Chronic stress is associated with cardiac remodeling; however the mechanisms have yet to be clarified. Objective: The purpose of this study was test the hypothesis that chronic stress promotes cardiac dysfunction associated to L-type calcium Ca2+ channel activity depression. Methods: Thirty-day-old male Wistar rats (70 - 100 g) were distributed into two groups: control (C) and chronic stress (St). The stress was consistently maintained at immobilization during 15 weeks, 5 times per week, 1h per day. The cardiac function was evaluated by left ventricular performance through echocardiography and by ventricular isolated papillary muscle. The myocardial papillary muscle activity was assessed at baseline conditions and with inotropic maneuvers such as: post-rest contraction and increases in extracellular Ca2+ concentration, in presence or absence of specific blockers L-type calcium channels. Results: The stress was characterized for adrenal glands hypertrophy, increase of systemic corticosterone level and arterial hypertension. The chronic stress provided left ventricular hypertrophy. The left ventricular and baseline myocardial function did not change with chronic stress. However, it improved the response of the papillary muscle in relation to positive inotropic stimulation. This function improvement was not associated with the L-type Ca2+ channel. Conclusion: Chronic stress produced cardiac hypertrophy; however, in the study of papillary muscle, the positive inotropic maneuvers potentiated cardiac function in stressed rats, without involvement of L-type Ca2+ channel. Thus, the responsible mechanisms remain unclear with respect to Ca2+ influx alterations. (Arq Bras Cardiol 2012;99(4):907-914)

The impact of the CACNA1C risk allele on limbic structures and facial emotions recognition in bipolar disorder subjects and healthy controls

Introduction: Impairments in facial emotion recognition (PER) have been reported in bipolar disorder (BD) during all mood states. FER has been the focus of functional magnetic resonance imaging studies evaluating differential activation of limbic regions. Recently, the alpha 1-C subunit of the L-type voltage-gated calcium channel (CACNA1C) gene has been described as a risk gene for BD and its Met allele found to increase CACNA1C mRNA expression. In healthy controls, the CACNA1C risk (Met) allele has been reported to increase limbic system activation during emotional stimuli and also to impact on cognitive function. The aim of this study was to investigate the impact of CACNA1C genotype on FER scores and limbic system morphology in subjects with BD and healthy controls. Material and methods: Thirty-nine euthymic BD I subjects and 40 healthy controls were submitted to a PER recognition test battery and genotyped for CACNA1C. Subjects were also examined with a 3D 3-Tesla structural imaging protocol. Results: The CACNA1C risk allele for BD was associated to FER impairment in BD, while in controls nothing was observed. The CACNA1C genotype did not impact on amygdala or hippocampus volume neither in BD nor controls. Limitations: Sample size. Conclusion: The present findings suggest that a polymorphism in calcium channels interferes FER phenotype exclusively in BD and doesn't interfere on limbic structures morphology. (C) 2012 Elsevier B.V. All rights reserved.

The effect of intrathecal gabapentin on neuropathic pain is independent of the integrity of the dorsolateral funiculus in rats

Aim: This study evaluates the contribution of inhibitory pain pathways that descend to the spinal cord through the dorsolateral funiculus (DLF) on the effect of intrathecal gabapentin against spinal nerve ligation (SNL)-induced behavioral hypersensitivity to mechanical stimulation in rats. Main method: Rats were submitted to a sham or complete ligation of the right LS and L6 spinal nerves and a sham or complete DLF lesion. Next, the changes induced by intrathecal administration of gabapentin on the paw withdrawal threshold of rats to mechanical stimulation were evaluated electronically. Key findings: Intrathecal gabapentin (200 mu g/5 mu l) that was injected 2 or 7 days after surgery fully inhibited the SNL-induced behavioral hypersensitivity to mechanical stimulation in sham DLF-Iesioned rats; gabapentin was effective against the SNL-induced behavioral hypersensitivity to mechanical stimulation also in DLF-Iesioned rats. Significance: The effect of intrathecally administered gabapentin against SNL-induced behavioral hypersensitivity to mechanical stimulation in rats does not depend on the activation of nerve fibers that descend to the spinal cord via the DLF. (C) 2012 Elsevier Inc. All rights reserved.

Aerial organ anatomy of Smilax syphilitica (Smilacaceae)

Smilax L. in Brazil is represented by 32 taxa and it is a taxonomically difficult genus because the plants are dioecious and show wide phenotypic variation. The analysis and use of leaf anatomy characters is recognized as a frequently successful taxonomic method to distinguish between individual taxon, when floral material is absent or minute differences in flowers and foliage exist such as in Smilax. The aim of this study was to characterize the anatomical features of the aerial organs in Smilax syphilitica collected from the Atlantic Rainforest, in Santa Teresa-ES and the Smilax aff syphilitica from the Amazon Rainforest, in Manaus, Brazil. For this, a total of three samples of Smilax were collected per site. Sample leaves and stems were fixed with FAA 50, embedded in historesin, sectioned on a rotary microtome, stained and mounted in synthetic resin. Additionally, histochemical tests were performed and cuticle ornamentation was analyzed with standard scanning electron microscopy. S. syphilitica and S. aff syphilitica differed in cuticle ornamentation, epidermal cell arrangement and wall thickness, stomata type and orientation, calcium oxalate crystal type, and position of stem thorns. Leaf blades of S. syphilitica from the Amazon Rainforest have a network of rounded ridges on both sides, while in S. aff syphilitica, these ridges are parallel and the spaces between them are filled with numerous membranous platelets. Viewed from the front, the epidermal cells of S. syphilitica have sinuous walls (even more pronounced in samples from the Amazon); while in S. aff syphilitica, these cells are also sinuous but elongated in the cross-section of the blade and arranged in parallel. Stomata of S. syphilitica are paracytic, whereas in S. aff syphilitica, are both paracytic and anisocytic, and their polar axes are directed towards the mid-vein. Calcium oxalate crystals in S. syphilitica are prisms, whereas in S. aff syphilitica, crystal sand. Thorns occur in nodes and internodes in S. syphilitica but only in internodes in S. aff syphilitica. These features have proven to be of diagnostic value and may support a separation into two species, but future studies are needed to confirm that S. aff syphilitica is indeed a new taxon. Rev. Biol. Trop. 60(3): 1137-1148. Epub 2012 September 01.

Stability-indicating methods for the enantioselective determination of dihydropyridines by high performance liquid chromatography and capillary electrophoresis

This paper presents simple, rapid, precise and accurate stability-indicating HPLC and CE methods, which were developed and validated for the determination of nitrendipine, nimodipine and nisoldipine. These drugs are calcium channel antagonists of the 1,4-dihydropyridine type which are used in the treatment of cardiovascular diseases. Experimental results showed a good linear correlation between the area and the concentration of drugs covering a relatively large domain of concentration in all cases. The linearity of the analytical procedures was in the range of 2.0-120.0 mu g mL-1 for nitrendipine, 1.0-100.0 mu g mL(-1) for nimodipine and 100.0-600.0 mu g mL(-1) for nisoldipine, the regression determination coefficient being higher than 0.99 in all cases. The proposed methods were found to have good precision and accuracy. The chemical stability of these drugs was determined under various conditions and the methods have shown adequate separation for their enantiomers and degradation products. In addition, degradation products produced as a result of stress studies did not interfere with the detection of the drugs' enantiomers and the assays can thus be considered stability-indicating.

CIRCULATION AND SALT INTRUSION IN THE PIACAGUERA CHANNEL, SANTOS (SP)

Analysis of thermohaline properties and currents sampled at an anchor station in the Piacaguera Channel (Santos Estuary) in the austral winter was made in terms of tidal (neap and spring tidal cycles) and non-tidal conditions, with the objective to characterize the stratification, circulation and salt transport due to the fortnightly tidal modulation. Classical methods of observational data analysis of hourly and nearly synoptic observations and analytical simulations of nearly steady-state salinity and longitudinal velocity profiles were used. During the neap tidal cycle the flood (v<0) and ebb (v>0) velocities varied in the range of -0.20 m/s to 0.30 m/s associated with a small salinity variation from surface to bottom (26.4 psu to 30.7 psu). In the spring tidal cycle the velocities increased and varied in the range of -0.40 m/s to 0.45 m/s, but the salinity stratification remained almost unaltered. The steady-state salinity and velocity profiles simulated with an analytical model presented good agreement (Skill near 1.0), in comparison with the observational profiles. During the transitional fortnightly tidal modulation period there was no changes in the channel classification (type 2a - partially mixed and weakly stratified), because the potential energy rate was to low to enhance the halocline erosion. These results, associated with the high water column vertical stability (RiL > 20) and the low estuarine Richardson number (RiE = 1.6), lead to the conclusions: i) the driving mechanism for the estuary circulation and mixing was mainly balanced by the fresh water discharge and the tidal forcing associated with the baroclinic component of the gradient pressure force; ii) there was no changes in the thermohaline and circulation characteristics due to the forthnigtly tidal modulation; and iii) the nearly steady-state of the vertical salinity and velocity profiles were well simulated with a theoretical classical analytical model.

Arginine induces GH gene expression by activating NOS/NO signaling in rat isolated hemi-pituitaries

The amino acid arginine (Arg) is a recognized secretagogue of growth hormone (GH), and has been shown to induce GH gene expression. Arg is the natural precursor of nitric oxide (NO), which is known to mediate many of the effects of Arg, such as GH secretion. Arg was also shown to increase calcium influx in pituitary cells, which might contribute to its effects on GH secretion. Although the mechanisms involved in the effects of Arg on GH secretion are well established, little is known about them regarding the control of GH gene expression. We investigated whether the NO pathway and/or calcium are involved in the effects of Arg on GH gene expression in rat isolated pituitaries. To this end, pituitaries from approximately 170 male Wistar rats (~250 g) were removed, divided into two halves, pooled (three hemi-pituitaries) and incubated or not with Arg, as well as with different pharmacological agents. Arg (71 mM), the NO donor sodium nitroprusside (SNP, 1 and 0.1 mM) and a cyclic guanosine monophosphate (cGMP) analogue (8-Br-cGMP, 1 mM) increased GH mRNA expression 60 min later. The NO acceptor hemoglobin (0.3 µM) blunted the effect of SNP, and the combined treatment with Arg and L-NAME (a NO synthase (NOS) inhibitor, 55 mM) abolished the stimulatory effect of Arg on GH gene expression. The calcium channel inhibitor nifedipine (3 µM) also abolished Arg-induced GH gene expression. The present study shows that Arg directly induces GH gene expression in hemi-pituitaries isolated from rats, excluding interference from somatostatinergic neurons, which are supposed to be inhibited by Arg. Moreover, the data demonstrate that the NOS/NO signaling pathway and calcium mediate the Arg effects on GH gene expression.

Circulation and salt intrusion in the Piaçaguera Channel, Santos (SP)

Analysis of thermohaline properties and currents sampled at an anchor station in the Piaçaguera Channel (Santos Estuary) in the austral winter was made in terms of tidal (neap and spring tidal cycles) and non-tidal conditions, with the objective to characterize the stratification, circulation and salt transport due to the fortnightly tidal modulation. Classical methods of observational data analysis of hourly and nearly synoptic observations and analytical simulations of nearly steady-state salinity and longitudinal velocity profiles were used. During the neap tidal cycle the flood (v<0) and ebb (v>0) velocities varied in the range of -0.20 m/s to 0.30 m/s associated with a small salinity variation from surface to bottom (26.4 psu to 30.7 psu). In the spring tidal cycle the velocities increased and varied in the range of -0.40 m/s to 0.45 m/s, but the salinity stratification remained almost unaltered. The steady-state salinity and velocity profiles simulated with an analytical model presented good agreement (Skill near 1.0), in comparison with the observational profiles. During the transitional fortnightly tidal modulation period there was no changes in the channel classification (type 2a - partially mixed and weakly stratified), because the potential energy rate was to low to enhance the halocline erosion. These results, associated with the high water column vertical stability (RiL >20) and the low estuarine Richardson number (RiE=1.6), lead to the conclusions: i) the driving mechanism for the estuary circulation and mixing was mainly balanced by the fresh water discharge and the tidal forcing associated with the baroclinic component of the gradient pressure force; ii) there was no changes in the thermohaline and circulation characteristics due to the forthnigtly tidal modulation; and iii) the nearly steady-state of the vertical salinity and velocity profiles were well simulated with a theoretical classical analytical model.

Diltiazem como alternativa ao betabloqueador na angiotomografia de artérias coronárias

FUNDAMENTO: A redução da frequência cardíaca (FC) na angiografia por tomografia das artérias coronarianas (ATCCor) é fundamental para a qualidade de imagem. A eficácia dos bloqueadores de cálcio como alternativas para pacientes com contraindicações aos betabloqueadores não foi definida. OBJETIVOS: Comparar a eficácia na redução da FC e variabilidade RR do metoprolol e diltiazem na ATCCor. MÉTODOS: Estudo prospectivo, randomizado, aberto, incluiu pacientes com indicação clínica de ATCCor, em ritmo sinusal, com FC>70bpm e sem uso de agentes que interferissem com a FC. Cinquenta pacientes foram randomizados para grupos: metoprolol IV 5-15 mg ou até FC≤60 bpm(M), e diltiazem IV 0,25-0,60mg/kg ou até FC≤60 bpm (D). Pressão arterial (PA) e FC foram aferidas na condição basal, 1min, 3min e 5min após agentes, na aquisição e após ATCCor. RESULTADOS: A redução da FC em valores absolutos foi maior no grupo M que no grupo D (1, 3, 5min, aquisição e pós-exame). A redução percentual da FC foi significativamente maior no grupo M apenas no 1 min e 3 min após início dos agentes. Não houve diferença no 5 min, durante a aquisição e após exame. A variabilidade RR percentual do grupo D foi estatisticamente menor do que a do grupo M durante a aquisição (variabilidade RR/ FC média da aquisição). Um único caso de BAV, 2:1 Mobitz I, revertido espontaneamente ocorreu (grupo D). CONCLUSÃO: Concluímos que o diltiazem é uma alternativa eficaz e segura aos betabloqueadores na redução da FC na realização de angiografia por tomografia computadorizada das artérias coronarianas. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)

Cardiac Rhythm Disturbances Associated with Amlodipine Acute Intoxication

Amlodipine is a dihydropyridine calcium channel antagonist extensively used for the treatment of arterial hypertension, with predominant effect on the peripheral vascular territory. In most cases of severe intoxication, important hypotension and reflex tachycardia are usually observed. We report a case of young man with severe amlodipine intoxication that developed important bradyarrhythmias, such as low atrial rhythm, prolonged PR interval, atrioventricular block, and left bundle branch block. These rhythm disturbances suggest that, during acute intoxication, dihydropyridine loses its selective action on the vascular territory and can depress automatism and conduction of cardiac electrical stimulus.

Oral Lesions in Renal Transplant

To prevent rejection of kidney transplants, patients must be kept in immunosuppressive therapy for a long time, which includes the use of drugs such as cyclosporine, azathioprine, cyclophosphamide, and prednisone. The action of these drugs reduces the general immune response of transplant patients and thus increases their susceptibility to infections. Moreover, these drugs increase the potential of developing lesions. Therefore, oral hygiene in kidney transplant recipients contributes to maintenance of the transplanted organ and its function. Thus, an investigation of oral lesions could be counted as a notable work. The aim of this study was to investigate oral lesions in a group of 21 kidney transplant patients under immunosuppressive therapy attended during a 1-year period in the Nephrology Department of the Federal University of Sergipe, Brazil. Data related to sex, age, etiology of renal disease, types of renal transplant, time elapsed after transplantation, immunosuppressive treatment, use of concomitant agents, and presence of oral lesions were obtained. All patients received a kidney transplant from a living donor, and the mean posttransplantation follow-up time was 31.6 months; 71.5% used triple immunosuppressive therapy with cyclosporine A, azathioprine, and prednisone. Ten patients were also treated with calcium-channel blockers. Of the 21 transplant patients, 17 (81%) presented oral lesions. Gingival overgrowth was the most common alteration, followed by candidiasis and superficial ulcers. One case of spindle cell carcinoma of the lower lip was observed. Oral cavity can harbor a variety of manifestations related to renal transplantation under immunosuppressive therapy.

Characterization of aflatoxigenic and non-aflatoxigenic strains of Aspergillus section Flavi isolated from corn grains of different geographic origins in Brazil

Aflatoxins can cause great economic losses and serious risks to humans and animals health. The largest aflatoxin producers belong to Aspergillus section Flavi and can occur naturally in food commodities. Studies showed that molecular tools as well as the type of sclerotia produced by the strains could be helpful for identification of Aspergillus species and could be correlated with levels of toxin production. The purpose of this work was to characterize the genetic diversity using AFLP technique, the type of sclerotia and the ability of aflatoxin production by isolated strains from corn of different origins in Brazil, and to verify whether qPCR based on aflR and aflP genes is appropriate for estimating the level of aflatoxin production. All the 75 strains were classified as A. flavus and the AFLP technique showed a wide intraspecific variability within them. Regarding sclerotia production, 34% were classified as S and 66% as L type. Among the aflatoxin-producers, 52.8% produced aflatoxin B-1, while 47.2% aflatoxins B-1 and B-2. Statistical analysis showed no correlation between sclerotia production and aflatoxigenicty, and no correlation between the phylogenetic clusters and aflatoxin production. Concerning the relative expression of aflR and aflP, Pearson's correlation test demonstrated low positive correlation between the expression of the aflR and aflP genes and the production of AFB(1) and AFB(2), but showed high positive correlation between aflR and aflP expression. In contrast to the other reference strains, A. oryzae ATCC 7282 showed no amplification of aflR and aflP. The results highlight the need for detection of reliable and reproducible markers with a high positive correlation with aflatoxin production.

The role of cytoskeleton, components of inositol phospholipid signaling pathway and iron in Ehrlichia canis in vitro proliferation

Ehrlichia canis, etiologic agent of Canine Monocytic Ehrlichiosis, is an obligatory intracellular bacterium that parasitizes monocytes and macrophages. In this study we analyzed the role of the cytoskeleton specifically actin microfilaments and microtubules, components of inositol phospholipid signaling pathway such as phospholipase C (PLC), protein kinase (PTK) and calcium channels as well as the role of iron in the E. canis proliferation in DH82 cells. Different inhibitory compounds were used for each component: Cytochalasin D (inhibits actin polymerization), Nocodazole (inhibits microtubule polymerization), Neomycin (PLC inhibitor), Genistein (PTK inhibitor), Verapamil (calcium channel blocker) and Deferoxamine (iron chelator). We observed a significant decrease in the total number of bacteria in infected cells treated suggesting that these cellular components analized are essentials to E. canis proliferation.

Tailored norbornene-based copolymer with systematic variation of norbornadiene as a crosslinker obtained via ROMP with alternative amine Ru catalysts

Copolymers of norbornene (NBE) with norbomadiene (NBD) were obtained via ROMP with [RuCl2(PPh3)(2)(L)] type complexes as initiators (1 for L = piperidine and 2 for L = 3,5-Me(2)piperidine). The reactions were performed using a fixed quantity of NBE (5000 equivalents/[Ru]) for different concentrations of NBD (500, 1000, 1500 and 2000 equivalents/ [Ru]) in CHCl3, initiated with ethyl diazoacetate at room temperature. The presence of NBD in the NBE chains was characterized by H-1 and C-13 NMR. Whereas the copolymer microstructure was influenced neither by the NBD quantity nor by the initiator type, the N-n and PDI values were improved when increasing the NBD quantity in the medium. When raising the NBD amount, DMA results indicated increased cross-linking with increasing T-g and E ' storage modulus, as well as the fact that SEM micrographs indicated decreased pore sizes in the porous isolated copolymers. (C) 2011 Elsevier Ltd. All rights reserved.

Models of passive and active dendrite motoneuron pools and their differences in muscle force control

Motoneuron (MN) dendrites may be changed from a passive to an active state by increasing the levels of spinal cord neuromodulators, which activate persistent inward currents (PICs). These exert a powerful influence on MN behavior and modify the motor control both in normal and pathological conditions. Motoneuronal PICs are believed to induce nonlinear phenomena such as the genesis of extra torque and torque hysteresis in response to percutaneous electrical stimulation or tendon vibration in humans. An existing large-scale neuromuscular simulator was expanded to include MN models that have a capability to change their dynamic behaviors depending on the neuromodulation level. The simulation results indicated that the variability (standard deviation) of a maintained force depended on the level of neuromodulatory activity. A force with lower variability was obtained when the motoneuronal network was under a strong influence of PICs, suggesting a functional role in postural and precision tasks. In an additional set of simulations when PICs were active in the dendrites of the MN models, the results successfully reproduced experimental results reported from humans. Extra torque was evoked by the self-sustained discharge of spinal MNs, whereas differences in recruitment and de-recruitment levels of the MNs were the main reason behind torque and electromyogram (EMG) hysteresis. Finally, simulations were also used to study the influence of inhibitory inputs on a MN pool that was under the effect of PICs. The results showed that inhibition was of great importance in the production of a phasic force, requiring a reduced co-contraction of agonist and antagonist muscles. These results show the richness of functionally relevant behaviors that can arise from a MN pool under the action of PICs.