The frequency of CD127(low) expressing CD4(+)CD25(high) T regulatory cells is inversely correlated with human T lymphotrophic virus type-1 (HTLV-1) proviral load in HTLV-1-infection and HTLV-1-associated myelopathy/tropical spastic paraparesis

Background: CD4(+)CD25(high) regulatory T (T(Reg)) cells modulate antigen-specific T cell responses, and can suppress anti-viral immunity. In HTLV-1 infection, a selective decrease in the function of T(Reg) cell mediated HTLV-1-tax inhibition of FOXP3 expression has been described. The purpose of this study was to assess the frequency and phenotype of T(Reg) cells in HTLV-1 asymptomatic carriers and in HTLV-1-associated neurological disease (HAM/TSP) patients, and to correlate with measures of T cell activation. Results: We were able to confirm that HTLV-1 drives activation, spontaneous IFN gamma production, and proliferation of CD4+ T cells. We also observed a significantly lower proportion of CTLA-4(+) T(Reg) cells (CD4(+)CD25(high) T cells) in subjects with HAM/TSP patients compared to healthy controls. Ki-67 expression was negatively correlated to the frequency of CTLA-4(+) T(Reg) cells in HAM/TSP only, although Ki-67 expression was inversely correlated with the percentage of CD127(low) T(Reg) cells in healthy control subjects. Finally, the proportion of CD127(low) T(Reg) cells correlated inversely with HTLV-1 proviral load. Conclusion: Taken together, the results suggest that T(Reg) cells may be subverted in HAM/TSP patients, which could explain the marked cellular activation, spontaneous cytokine production, and proliferation of CD4(+) T cells, in particular those expressing the CD25(high)CD127(low) phenotype. T(Reg) cells represent a potential target for therapeutic intervention for patients with HTLV-1-related neurological diseases.

The cerebral sulci and gyri

The aim of this study was to describe in detail the microanatomy of the cerebral sulci and gyri, clarifying the nomenclature for microneurosurgical purposes. An extensive review of the literature regarding the historical, evolutionary, embryological, and anatomical aspects pertinent to human cerebral sulci and gyri was conducted, with a special focus on microneuroanatomy issues in the field of neurosurgery. An intimate knowledge of the cerebral sulci and gyri is needed to understand neuroimaging studies, as well as to plan and execute current microneurosurgical procedures. (DOI: 10.3171/2009.11.FOCUS09245)

Detection of dengue virus in saliva and urine by real time RT-PCR

Early diagnosis of dengue virus (DENV) infection is important for patient management and control of dengue outbreaks. The objective of this study was to analyze the usefulness of urine and saliva samples for early diagnosis of DENV infection by real time RT-PCR. Two febrile patients, who have been attended at the General Hospital of the School of Medicine of Ribeirao Preto, Sao Paulo University were included in the study. Serum, urine and saliva samples collected from both patients were subjected to real time RT-PCR for DENV detection and quantification. Dengue RNA was detected in serum, urine and saliva samples of both patients. Patient 1 was infected with DENV-2 and patient 2 with DENV-3. Data presented in this study suggest that urine and saliva could be used as alternative samples for early diagnosis of dengue virus infection when blood samples are difficult to obtain, e.g.,in newborns and patients with hemorrhagic syndromes.

Thunderclap headache attributed to reversible cerebral vasoconstriction: view and review

Thunderclap headache attributed to reversible cerebral vasoconstriction (THARCV) is a syndrome observed in a number of reported cases. In this article we reviewed this new headache entity (idiopathic form) using the clinical-radiological findings of 25 reported patients. In this series of patients 72% were women, the mean age at the onset of first headache episode was 39.4 +/- 2.3 years. In addition to the sine quanon condition of being abrupt and severe (thunderclap) at the onset, the headache was usually described as being explosive, excruciating, or crushing. The feature of pulsatility, accompanied or not by nausea was described by 80% of the patients. Forty percent of the cases manifested vomiting and 24% photophobia. Usually the headache was generalized, and in three cases it was unilateral at least at the onset. In 21 of 25 patients (84%) there was at least one recurrence or a sudden increase in the intensity of the headache. A past history of migraine was present in 52% of the patients. Precipitating factors were identified in 56% of the patients. Sexual intercourse was described by six patients. Of the 25 patients with THARCV syndrome studied, 12 (48%) developed focal neurological signs, transitory ischemic attack (n = 1), or ischemic stroke (n = 11, 44%), and two (8%) of them manifested seizures. The THARCV syndrome is a neurological disturbance perhaps more frequent than expected, preferentially affecting middle aged female migraineurs, and having an unpredictable prognosis, either showing a benign course or leading to stroke.

First Report on Rotenoids as Neurotoxic Principles of Seeds from Aeschynomene indica (Leguminosae)

Toxic principles from seeds of Aeschynomene indica collected in Brazil were analyzed. Dalpanol, 12 alpha-hydroxydalpanol and 11-hydroxydalpanol were identified using (1)H NMR in A. indica for the first time. 11-hydroxydalpanol has not been previously reported in the existing literature. Furthermore these rotenoids are likely the toxic principles that cause neurological signs in mice.

Hyperbaric Oxygen Prevents Early Death Caused by Experimental Cerebral Malaria

Background: Cerebral malaria (CM) is a syndrome characterized by neurological signs, seizures and coma. Despite the fact that CM presents similarities with cerebral stroke, few studies have focused on new supportive therapies for the disease. Hyperbaric oxygen (HBO) therapy has been successfully used in patients with numerous brain disorders such as stroke, migraine and atherosclerosis. Methodology/Principal Findings: C57BL/6 mice infected with Plasmodium berghei ANKA (PbA) were exposed to daily doses of HBO (100% O(2), 3.0 ATA, 1-2 h per day) in conditions well-tolerated by humans and animals, before or after parasite establishment. Cumulative survival analyses demonstrated that HBO therapy protected 50% of PbA-infected mice and delayed CM-specific neurological signs when administrated after patent parasitemia. Pressurized oxygen therapy reduced peripheral parasitemia, expression of TNF-alpha, IFN-gamma and IL-10 mRNA levels and percentage of gamma delta and alpha beta CD4(+) and CD8(+) T lymphocytes sequestered in mice brains, thus resulting in a reduction of blood-brain barrier (BBB)dysfunction and hypothermia. Conclusions/Significance: The data presented here is the first indication that HBO treatment could be used as supportive therapy, perhaps in association with neuroprotective drugs, to prevent CM clinical outcomes, including death.

VEGF Promotes Malaria-Associated Acute Lung Injury in Mice

The spectrum of the clinical presentation and severity of malaria infections is broad, ranging from uncomplicated febrile illness to severe forms of disease such as cerebral malaria (CM), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), pregnancy-associated malaria (PAM) or severe anemia (SA). Rodent models that mimic human CM, PAM and SA syndromes have been established. Here, we show that DBA/2 mice infected with P. berghei ANKA constitute a new model for malaria-associated ALI. Up to 60% of the mice showed dyspnea, airway obstruction and hypoxemia and died between days 7 and 12 post-infection. The most common pathological findings were pleural effusion, pulmonary hemorrhage and edema, consistent with increased lung vessel permeability, while the blood-brain barrier was intact. Malaria-associated ALI correlated with high levels of circulating VEGF, produced de novo in the spleen, and its blockage led to protection of mice from this syndrome. In addition, either splenectomization or administration of the anti-inflammatory molecule carbon monoxide led to a significant reduction in the levels of sera VEGF and to protection from ALI. The similarities between the physiopathological lesions described here and the ones occurring in humans, as well as the demonstration that VEGF is a critical host factor in the onset of malaria-associated ALI in mice, not only offers important mechanistic insights into the processes underlying the pathology related with malaria but may also pave the way for interventional studies.

Identification of protein-coding and non-coding RNA expression profiles in CD34(+) and in stromal cells in refractory anemia with ringed sideroblasts

Background: Myelodysplastic syndromes (MDS) are a group of clonal hematological disorders characterized by ineffective hematopoiesis with morphological evidence of marrow cell dysplasia resulting in peripheral blood cytopenia. Microarray technology has permitted a refined high-throughput mapping of the transcriptional activity in the human genome. Non-coding RNAs (ncRNAs) transcribed from intronic regions of genes are involved in a number of processes related to post-transcriptional control of gene expression, and in the regulation of exon-skipping and intron retention. Characterization of ncRNAs in progenitor cells and stromal cells of MDS patients could be strategic for understanding gene expression regulation in this disease. Methods: In this study, gene expression profiles of CD34(+) cells of 4 patients with MDS of refractory anemia with ringed sideroblasts (RARS) subgroup and stromal cells of 3 patients with MDS-RARS were compared with healthy individuals using 44 k combined intron-exon oligoarrays, which included probes for exons of protein-coding genes, and for non-coding RNAs transcribed from intronic regions in either the sense or antisense strands. Real-time RT-PCR was performed to confirm the expression levels of selected transcripts. Results: In CD34(+) cells of MDS-RARS patients, 216 genes were significantly differentially expressed (q-value <= 0.01) in comparison to healthy individuals, of which 65 (30%) were non-coding transcripts. In stromal cells of MDS-RARS, 12 genes were significantly differentially expressed (q-value <= 0.05) in comparison to healthy individuals, of which 3 (25%) were non-coding transcripts. Conclusions: These results demonstrated, for the first time, the differential ncRNA expression profile between MDS-RARS and healthy individuals, in CD34(+) cells and stromal cells, suggesting that ncRNAs may play an important role during the development of myelodysplastic syndromes.

ABNORMAL EXPRESSION OF VOLTAGE-GATED SODIUM CHANNELS Nav1.7, Nav1.3 AND Nav1.8 IN TRIGEMINAL NEURALGIA

Voltage-gated sodium channels have been implicated in acute and chronic neuropathic pain. Among subtypes, Nav1.7 single mutations can cause congenital indifference to pain or chronic neuropathic pain syndromes, including paroxysmal ones. This channel is co-expressed with Nav1.8, which sustains the initial action potential; Nav1.3 is an embrionary channel which is expressed in neurons after injury, as in neuropathic conditions. Few studies are focused on the expression of these molecules in human tissues having chronic pain. Trigeminal neuralgia (TN) is an idiopathic paroxysmal pain treated with sodium channel blockers. The aim of this study was to investigate the expression of Nav1.3, Nav1.7 and Nav1.8 by RT-PCR in patients with TN, compared to controls. The gingival tissue was removed from the correspondent trigeminal area affected. We found that Nav1.7 was downregulated in TN (P=0.017) and Nav1.3 was upregulated in these patients (P=0.043). We propose a physiopathological mechanism for these findings. Besides vascular compression of TN, this disease might be also a channelopathy. (C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.

EIS study of Ti-23Ta alloy in artificial saliva

Although titanium and Ti-6Al-4V alloy have been widely used as dental materials, possible undesirable effects such as cytotoxic reactions and neurological disorder due to metal release led to the development of more corrosion resistant and V and Al free titanium alloys, containing Nb, Zr, Mo and Ta atoxic elements. Fluoride containing products used in the prevention of plaque formation and dental caries can affect the stability of the passive oxide films formed on the Ti alloys. In this work, the corrosion behaviour of the new Ti-23Ta alloy has been evaluated in artificial saliva of different pH and fluoride concentration using electrochemical impedance spectroscopy. Electrochemical impedance spectroscopy study showed that the oxide film formed on the alloy in artificial saliva consists of an inner compact film and an outer porous layer. The corrosion resistance of Ti-23Ta alloy which is reduced by increasing F concentration or decreasing pH is related to the resistance of the inner compact layer. The presence of fluoride and low pH of the saliva enhance the porosity of the oxide film and its dissolution.

Corrosion behavior of Ti-xNb-13Zr alloys in Ringer`s solution

Ti-6Al-4V alloy has been widely used in restorative surgery due to its high corrosion resistance and biocompatibility. Nevertheless, some studies showed that V and Al release in the organism might induce cytotoxic effects and neurological disorders, which led to the development of V-free alloys and both V- and Al-free alloys containing Nb, Zr, Ta, or Mo. Among these alloys, Ti-13Nb-13Zr alloy is promising due to its better biomechanical compatibility than Ti-6Al-4V. In this work, the corrosion behavior of Ti, Ti-6Al-4V, and Ti-xNb-13Zr alloys (x=5, 13, and 20) was evaluated in Ringer`s solution (pH 7.5) at 37 degrees C through open-circuit potential measurements, potentiodynamic polarization, and electrochemical impedance spectroscopy. Spontaneous passivity was observed for all materials in this medium. Low corrosion current densities (in the order of 10(-7) A/cm(2)) and high impedance values (in the order of 10(5) Omega cm(2) at low frequencies) indicated their high corrosion resistance. EIS results showed that the passivating films were constituted of an outer porous layer (very low resistance) and an inner compact layer (high resistance), the latter providing the corrosion resistance of the materials. There was evidence that the Ti-xNb-13Zr alloys were more corrosion resistant than both Ti and Ti-6Al-4V in Ringer`s solution.

Upper limb assessment in tetraplegia: clinical, functional and kinematic correlations

The aim of this study was to correlate clinical and functional evaluations with kinematic variables of upper limp reach-to-grasp movement in patients with tetraplegia. Twenty chronic patients were selected to perform reach-to-grasp kinematic assessment using a target placed at a distance equal to the arm`s length. Kinematic variables (hand peak velocity, movement time, percent time-to-maximal velocity, index of curvature, number of peaks, and joint range of motion) were correlated to clinical (Standard Neurological Classification of Spinal Cord Injury-American Spinal Injury Association) and functional [Functional Independence Measure (FIM) and Spinal Cord Independence Measure II (SCIM II)) evaluation scores. Twenty control participants were also selected to obtain normal reference parameters. There was a positive correlation between total motor index and FIM (r=0.6089; P=0.0044) and SCIM II (r=0.5229; P=0.018). Both functional scores showed positive correlation with each other (r=0.8283; P<0.0001). A correlation was also observed between the right and left motor indices, the motor AM, and the SCIM II in most of the reach-to-grasp kinematic variables studied (hand peak velocity, movement time, index of curvature, and number of peaks). In contrast, for the joint range of motion (shoulder, elbow, and wrist), only the wrist in the horizontal plane showed correlation with clinical variables. This study shows that muscle strength assessed by the American Spinal Injury Association motor index influences the reach-to-grasp kinematic variables of patients with tetraplegia. However, the functional assessments did not present the same influence.

Denoising swallowing sound to improve the evaluator`s qualitative analysis

Swallowing dynamics involves the coordination and interaction of several muscles and nerves which allow correct food transport from mouth to stomach without laryngotracheal penetration or aspiration. Clinical swallowing assessment depends on the evaluator`s knowledge of anatomic structures and of neurophysiological processes involved in swallowing. Any alteration in those steps is denominated oropharyngeal dysphagia, which may have many causes, such as neurological or mechanical disorders. Videofluoroscopy of swallowing is presently considered to be the best exam to objectively assess the dynamics of swallowing, but the exam needs to be conducted under certain restrictions, due to patient`s exposure to radiation, which limits periodical repetition for monitoring swallowing therapy. Another method, called cervical auscultation, is a promising new diagnostic tool for the assessment of swallowing disorders. The potential to diagnose dysphagia in a noninvasive manner by assessing the sounds of swallowing is a highly attractive option for the dysphagia clinician. Even so, the captured sound has an amount of noise, which can hamper the evaluator`s decision. In that way, the present paper proposes the use of a filter to improve the quality of audible sound and facilitate the perception of examination. The wavelet denoising approach is used to decompose the noisy signal. The signal to noise ratio was evaluated to demonstrate the quantitative results of the proposed methodology. (C) 2007 Elsevier Ltd. All rights reserved.

Enterotoxigenic and genetic profiles of Bacillus cereus strains of food origin in Brazil

In Brazil. the incidence of Bacillus cereus outbreaks is unknown, and there is little information about B. cereus occurrence in food. In addition, data on toxin production and genetic characterization of the B. cereus isolates cannot be found. This pathogen causes two distinct types of toxin-mediated foodborne illnesses known as diarrheal and emetic syndromes. Diarrheal syndrome has been linked to three different enterotoxins: two protein complexes, hemolysin BL (HBL) and nonhemolytic enterotoxin (NHE); and an enterotoxic protein, cytotoxin K (cytK). Emetic syndrome is related to cereulide, a toxin encoded by the ces gene. In this study, NHE and HBL production capacities of 155 strains of B. cereus isolated from Brazilian food products were evaluated with an immunoassay. Strains were also tested for the presence of the genes of the HBL and NHE complexes, cytK, cytK-1, cytK-2, and ces, using PCR. HBL was detected in 105 (67.7%) strains and NHE in 154 (99.4%) strains. All the strains harbored at least one gene of the NHE complex, while 96.1% of them were positive for at least one of those of the HBL complex. Genes cytK1 and ces were not detected. All strains showed toxigenic capacity and could represent a risk for consumers if good practices are not followed. This is the first report on toxigenic and genetic profiles of B. cereus strains isolated in Brazil.

Timing and Dose of Statin Therapy Define Its Impact on Inflammatory and Endothelial Responses During Myocardial Infarction

Objective-Clinical trials of statins during myocardial infarction (MI) have differed in their therapeutic regimes and generated conflicting results. This study evaluated the role of the timing and potency of statin therapy on its potential mechanisms of benefit during MI. Methods and Results-ST-elevation MI patients (n = 125) were allocated into 5 groups: no statin; 20, 40, or 80 mg/day simvastatin starting at admission; or 80 mg/day simvastatin 48 hours after admission. After 7 days, all patients switched their treatment to 20 mg/day simvastatin for an additional 3 weeks and then underwent flow-mediated dilation in the brachial artery. As of the second day, C-reactive protein (CRP) differed between non-statin users (12.0 +/- 4.1 mg/L) and patients treated with 20 (8.5 +/- 4.0 mg/L), 40 (3.8 +/- 2.5 mg/L), and 80 mg/day (1.4 +/- 1.5 mg/L), and the daily differences remained significant until the seventh day (P < 0.0001). The higher the statin dose, the lower the elevation of interleukin-2 and tumor necrosis factor-alpha, the greater the reduction of 8-isoprostane and low-density lipoprotein(-), and the greater the increase in nitrate/nitrite levels during the first 5 days (P < 0.001). Later initiation of statin was less effective than its early introduction in relation to attenuation of CRP, interleukin-2, tumor necrosis factor-alpha, 8-isoprostane, and low-density lipoprotein(-), as well as in increase in nitrate/nitrite levels (P < 0.0001). At the 30th day, there was no longer a difference in lipid profile or CRP between groups; the flow-mediated dilation, however, was proportional to the initial statin dose and was higher for those who started the treatment early (P = 0.001). Conclusion-This study demonstrates that the timing and potency of statin treatment during MI are key elements for their main mechanisms of benefit.