Kallikrein-Kinin System Mediated Inflammation in Alzheimer`s Disease In Vivo

The Kallikrein-Kinin System (KKS) has been associated to inflammatory and immunogenic responses in the peripheral and central nervous system by the activation of two receptors, namely B1 receptor and B2 receptor. The B1 receptor is absent or under-expressed in physiological conditions, being up-regulated during tissue injury or in the presence of cytokines. The B2 receptor is constitutive and mediates most of the biological effects of kinins. Some authors suggest a link between the KKS and the neuroinflammation in Alzheimer`s disease (AD). We have recently described an increase in bradykinin (BK) in the cerebrospinal fluid and in densities of B1 and B2 receptors in brain areas related to memory, after chronic infusion of amyloid-beta (A beta) peptide in rats, which was accompanied by memory disruption and neuronal loss. Mice lacking B1 or B2 receptors presented reduced cognitive deficits related to the learning process, after acute intracerebroventricular (i.c.v). administration of A. Nevertheless, our group showed an early disruption of cognitive function by i.c.v. chronic infusion of A beta after a learned task, in the knock-out B2 mice. This suggests a neuroprotective role for B2 receptors. In knock-out B1 mice the memory disruption was absent, implying the participation of this receptor in neurodegenerative processes. The acute or chronic infusion of A beta can lead to different responses of the brain tissue. In this way, the proper involvement of KKS on neuroinflammation in AD probably depends on the amount of A beta injected. Though, BK applied to neurons can exert inflammatory effects, whereas in glial cells, BK can have a potential protective role for neurons, by inhibiting proinflammatory cytokines. This review discusses this duality concerning the KKS and neuroinflammation in AD in vivo.

Change in central kinin B2 receptor density after exercise training in rats

Cardiovascular responses elicited by the stimulation of kinin B2 receptors in the IV cerebral ventricle paratrigeminal nucleus or in the thoracic spinal cord are similar to those observed during an exercise bout Considering that the kalikrein-kinin system (KKS) could act on the cardiovascular modulation during behavioral responses as physical exercise or stress this study evaluated the central B2 receptor densities of Wistar (W) and spontani ously hypertensive rats (SHR) after chronic moderate exercise Animals we re exercise-trained for ten weeks on a treadmill Afterwards systolic blood pressure decreased in both trained strains Animals were killed and the medulla and spinal cord extracted for B2 receptor autoradiography Trained animals were compared to their sedentary controls Sedentary groups showed specific binding sites for Hoe-140 (fmol/mg of tissue) in laminas 1 and 2 of the spinal cord nucleus of the solitary tract (NTS) area postrema (AP) spinal trigeminal tract (sp5) and paratrigeminal nucleus (Pa5) In trained W a significant increase (p<0 05) in specific binding was observed in the Pa5 (31 3%) and NTS (28 2%) Trained SHR showed a significant decrease in n ceptor density in lamina 2 (21 9%) of the thoracic spinal cord and an increase in specific binding in Pa5 (36 1%) We suggest that in the medulla chronic exercise could hyper stimulate the KKS enhancing their efficiency through the increase of B2 receptor density involving this receptor in central cardiovascular control during exercise or stress In the lamina 2 B2 receptor might be involved in the exercise-induced hypotension (C) 2010 Elsevier BV All rights reserved

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.

Sagittal spinal alignment in paraplegics: a new paradigm for the rehabilitation under neuromuscular electrical stimulation

Study design: Radiographic analysis of sagittal spinal alignment of paraplegics in a standing position under surface neuromuscular electrical stimulation (NMES). Objectives: Describing the radiographic parameters of the sagittal spinal alignment of paraplegics going through a rehabilitation program with NMES. Setting: The University Hospital`s Ambulatory (UNICAMP), Campinas, Sao Paulo, Brazil. Methods: Panoramic X-ray images in profile were taken for 10 paraplegics. All patients participated in the rehabilitation program and were able to perform gait through NMES of the femoral quadriceps muscles. The radiographic parameters used for the analysis were the same as those described in the literature for healthy people. The results were didactically organized into three groups: anatomical shape of the spine, morphology and kinetics of the pelvis and spinopelvic alignment. Results: The physiological curvature of the spine in paraplegics showed average values similar to those described in the literature for healthy patients. The inversion of the pelvic tilt and the increase in the sacral slope were defined by the anterior backward rotation of the pelvis. The existing theoretical mathematical formulas that define lumbar lordosis, pelvic incidence and pelvic tilt showed normal values, despite the anterior intense sagittal imbalance. Conclusions: The adaptive posture of the spine in paraplegics standing through the stimulation of the femoral quadriceps does not allow for a neutral sagittal alignment. This novel radiographic detailed description of the various segments of the spine can be of assistance toward the understanding of the global postural control for such subjects. Spinal Cord (2010) 48, 251-256; doi: 10.1038/sc.2009.123; published online 29 September 2009

A hybrid system for upper limb movement restoration in quadriplegics

Generally, quadriplegic individuals have difficulties performing object manipulation. Toward satisfactory manipulation, reach and grasp movements must be performed with voluntary control, and for that, grasp force feedback is essential. A hybrid system aiming at partial upper limb sensory-motor restoration for quadriplegics was built. Such device is composed of an elbow dynamic orthosis that provides elbow flexion/extension (range was approximately from 20 degrees to 120 degrees, and average angular speed was approximately 15 degrees/s) with forearm support, a wrist static orthosis and neuromuscular electrical stimulation for grasping generation, and a glove with force sensors that allows grasping force feedback. The glove presents two user interface modes: visual by light emitting diodes or audio emitted by buzzer. Voice control of the entire system (elbow dynamic orthosis and electrical stimulator) is performed by the patient. The movements provided by the hybrid system, combined with the scapular and shoulder movements performed by the patient, can aid quadriplegic individuals in tasks that involve reach and grasp movements.

Electrical stimulation and treadmill gait in tetraplegic patients: assessment of its effects on the knee with magnetic resonance imaging

Study design: Evaluation of knees of tetraplegic patients who have been walking for several months with the aid of a system that involves neuromuscular stimulation, treadmill and a harness support device. Objectives: To investigate if the training program could cause knee injury to tetraplegic patients. Setting: Hospital das Clinicas - UNICAMP. Campinas-SP, Brazil. Methods: Nine patients were evaluated. Clinical exam and magnetic resonance images (MRIs) were used for evaluation. MRIs were taken before and after the training program, in a 6-month interval for each patient. There were two sessions of training every week. Each session lasted 20 min. Results: No severe clinical abnormality was observed in any patient. Mild knee injury was observed in four of nine patients studied. Conclusions: Tetraplegic patients undergoing treadmill gait training deserve a close follow-up to prevent knee injury.

Variability on red blood cell transfusion practices among Brazilian neonatal intensive care units

BACKGROUND: Guidelines for red blood cell (RBC) transfusions exist; however, transfusion practices vary among centers. This study aimed to analyze transfusion practices and the impact of patients and institutional characteristics on the indications of RBC transfusions in preterm infants. STUDY DESIGN AND METHODS: RBC transfusion practices were investigated in a multicenter prospective cohort of preterm infants with a birth weight of less than 1500 g born at eight public university neonatal intensive care units of the Brazilian Network on Neonatal Research. Variables associated with any RBC transfusions were analyzed by logistic regression analysis. RESULTS: Of 952 very-low-birth-weight infants, 532 (55.9%) received at least one RBC transfusion. The percentages of transfused neonates were 48.9, 54.5, 56.0, 61.2, 56.3, 47.8, 75.4, and 44.7%, respectively, for Centers 1 through 8. The number of transfusions during the first 28 days of life was higher in Center 4 and 7 than in other centers. After 28 days, the number of transfusions decreased, except for Center 7. Multivariate logistic regression analysis showed higher likelihood of transfusion in infants with late onset sepsis (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.8-4.4), intraventricular hemorrhage (OR, 9.4; 95% CI, 3.3-26.8), intubation at birth (OR, 1.7; 95% CI, 1.0-2.8), need for umbilical catheter (OR, 2.4; 95% CI, 1.3-4.4), days on mechanical ventilation (OR, 1.1; 95% CI, 1.0-1.2), oxygen therapy (OR, 1.1; 95% CI, 1.0-1.1), parenteral nutrition (OR, 1.1; 95% CI, 1.0-1.1), and birth center (p < 0.001). CONCLUSIONS: The need of RBC transfusions in very-low-birth-weight preterm infants was associated with clinical conditions and birth center. The distribution of the number of transfusions during hospital stay may be used as a measure of neonatal care quality.

Body composition and quality of life (QoL) of the elderly offered by the ""University Third Age`` (UTA) in Brazil

The investigation of the factors that interfere in the well-being of the elderly and their QoL can provide theoretical and methodological subsidies in structuring actions and policies in the health area, in order to fulfill the needs of that population. In this descriptive transversal study, body composition and QoL of elderly women at the UTA program in Piracicaba (Sao Paulo, Brazil) were verified. The participants were 81 women from UTA, and the general levels of physical activity were evaluated, as well as body weight (BW), height, and bodymass index (BMI). The waist circumference (WC) was measured at the level of the umbilical scar and the body composition by impedance (BIA 310e). QoL was verified by means of WHOQOL-Bref and statistical analysis developed with the SAS program. The decrease of weight, height, BMI, and fat-free mass (FFM) was observed among the several age groups, although with no significant difference. The average levels of the general QoL scores and physical, psychological and environmental domains decreased in higher age groups, but social domains showed the opposite result. This fact can be a particular characteristic of the UTA group, and factors the influence such behavior are yet to be studied. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Budlein A from Viguiera robusta inhibits leukocyte-endothelial cell interactions, adhesion molecule expression and inflammatory mediators release

Budlein A has been reported to exert some analgesic and anti-inflammatory properties. In this study, we have evaluated its effect on LPS-induced leukocyte recruitment in vivo and the mechanisms involved in its anti-inflammatory activity. In vivo, intravital videomicroscopy was used to determine the effects of budlein A on LPS-induced leukocyte-endothelial cell interactions in the murine cremasteric microcirculation. In vitro, the effects of budlein A on LPS-induced cytokine, chemokine and nitrites release, T-cell proliferative response as well as cell adhesion molecule expression (CAM) were evaluated. In vivo, intraperitoneal administration of budlein A (2.6 mM/kg) caused a significant reduction of LPS-induced leukocyte rolling flux, adhesion and emigration by 84, 92 and 96% respectively. In vitro, T-cell proliferative response was also affected by budlein A. When murine J774 macrophages were incubated with the sesquiterpene lactone, LPS-induced IL-1 beta, tumor necrosis factor-alpha (TNF-alpha) and keratinocyte-derived chemokine (KC) release were concentration-dependently inhibited. In human umbilical vein endothelial cells (HUVECs), budlein A also reduced the production of TNF-alpha, monocyte chemoattractant protein-1 (MCP-1), IL-8, nitrites and CAM expression elicited by LPS. Budlein A is a potent inhibitor of LPS-induced leukocyte accumulation in vivo. This effect appears to be mediated through inhibition of cytokine and chemokine release and down-regulation of CAM expression. Thus, it has potential therapeutic interest for the control of leukocyte recruitment that occurs in different inflammatory disorders. (C) 2009 Elsevier GrnbH. All rights reserved.

Interaction of 10-(octyloxy) decyl-2-(trimethylammonium) ethyl phosphate with mimetic membranes and cytotoxic effect on leukemic cells

10-(Octyloxy) decyl-2-(trimethylammonium) ethyl phosphate (ODPC) is an alkylphospholipid that can interact with cell membranes because of its amphiphilic character. We describe here the interaction of ODPC with liposomes and its toxicity to leukemic cells with an ED-50 of 5.4, 5.6 and 2.9 pM for 72 h of treatment for inhibition of proliferation of NB4, U937 and K562 cell lines, respectively, and lack of toxicity to normal hematopoietic progenitor cells at concentrations up to 25 pM. The ED-50 for the non-malignant HEK-293 and primary human umbilical vein endothelial cells (HUVEC) was 63.4 and 60.7 mu M, respectively. The critical micellar concentration (CMC) of ODPC was 200 mu M. Dynamic light scattering indicated that dipalmitoylphosphatidylcholine (DPPC) liposome size was affected only above the CMC of ODPC. Differential calorimetric scanning (DCS) of liposomes indicated a critical transition temperature (T(c)) of 41.5 degrees C and an enthalpy (Delta H) variation of 7.3 kcal mol(-1). The presence of 25 mu M ODPC decreased T(c) and Delta H to 393 degrees C and 4.7 kcal mol(-1), respectively. ODPC at 250 mu M destabilized the liposomes (36.3 degrees C. 0.46 kcal mol(-1)). Kinetics of 5(6)-carboxyfluorescein (CF) leakage from different liposome systems indicated that the rate and extent of CF release depended on liposome composition and ODPC concentration and that above the CMC it was instantaneous. Overall, the data indicate that ODPC acts on in vitro membrane systems and leukemia cell lines at concentrations below its CMC, suggesting that it does not act as a detergent and that this effect is dependent on membrane composition. (C) 2010 Elsevier B.V. All rights reserved.

EEG-based Brain-Computer Interfaces: An Overview of Basic Concepts and Clinical Applications in Neurorehabilitation

Some patients are no longer able to communicate effectively or even interact with the outside world in ways that most of us take for granted. In the most severe cases, tetraplegic or post-stroke patients are literally `locked in` their bodies, unable to exert any motor control after, for example, a spinal cord injury or a brainstem stroke, requiring alternative methods of communication and control. But we suggest that, in the near future, their brains may offer them a way out. Non-invasive electroencephalogram (EEG)-based brain-computer interfaces (BCD can be characterized by the technique used to measure brain activity and by the way that different brain signals are translated into commands that control an effector (e.g., controlling a computer cursor for word processing and accessing the internet). This review focuses on the basic concepts of EEG-based BC!, the main advances in communication, motor control restoration and the down-regulation of cortical activity, and the mirror neuron system (MNS) in the context of BCI. The latter appears to be relevant for clinical applications in the coming years, particularly for severely limited patients. Hypothetically, MNS could provide a robust way to map neural activity to behavior, representing the high-level information about goals and intentions of these patients. Non-invasive EEG-based BCIs allow brain-derived communication in patients with amyotrophic lateral sclerosis and motor control restoration in patients after spinal cord injury and stroke. Epilepsy and attention deficit and hyperactive disorder patients were able to down-regulate their cortical activity. Given the rapid progression of EEG-based BCI research over the last few years and the swift ascent of computer processing speeds and signal analysis techniques, we suggest that emerging ideas (e.g., MNS in the context of BC!) related to clinical neuro-rehabilitation of severely limited patients will generate viable clinical applications in the near future.

T-Shaped Microsuture: A New Suture Technique for Laryngeal Microsurgery

To describe a new suture technique for laryngeal microsurgery and to test its applicability in human cadaver larynges. The new technique was experimentally tested in freshly excised human larynges fixed to a larynx holder appropriate for the simulation of laryngeal microsurgery. A mucosal flap was created in the vocal fold for the fabrication of a pocket for subepithelial fat implantation, and the wound edges were then brought together and sutured using the proposed technique. The time necessary for suture was measured with a stopwatch for five successive sutures performed by one of the surgeons. The presence or absence of mucosal rupture was determined for five sutures performed by two surgeons, for a total of 10 sutures. The sutures were performed without the help of an assistant, with no laceration of the mucosa being observed in any of the attempts, and within a relatively short period of time even without previous training. The sutures performed permitted the implanted fat to remain stable under the mucosal flap. Conclusions: the new suture technique is an easy procedure, which can be performed by a single surgeon under microscopic vision, with a low risk of tissue rupture. The technique does not markedly prolong the duration of surgery and a single suture thread can be used for the fabrication of more than one stitch.

Cardiac troponin T as a biochemical marker of cardiac dysfunction and ductus venosus Doppler velocimetry

Objectives: The aim of this study was to determine the correlation between ductus venosus (DV) Doppler velocimetry and fetal cardiac troponin T (cTnT). Study design: Between March 2007 and March 2008, 89 high-risk pregnancies were prospectively studied. All patients delivered by cesarean section and the Doppler exams were performed on the same day. Multiple regression included the following variables: maternial age, parity, hypertension, diabetes, gestational age at delivery, umbilical artery (UA) S/D ratio, diagnosis of absent or reversed end-diastolic flow velocity (AREDV) in the UA, middle cerebral artery (MCA) pulsatility index (131), and DV pulsatility index for veins (PIV). Immediately after delivery, UA blood samples were obtained for the measurement of pH and cTnT levels. Statistical analysis included the Kruskal-Wallis test and multiple regressions. Results: The results showed a cTnT concentration at birth >0.05 ng/ml in nine (81.8%) of AREDV cases, a proportion significantly higher than that observed in normal UA S/D ratio and UA S/D ratio >p95 with positive diastolic blood flow (7.7 and 23.1%, respectively, p < 0.001). A positive correlation Was found between abnormal DV-PIV and elevated cTnT levels in the UA. Multiple regression identified DV-PIV and a diagnosis of AREDV as independent factors associated with abnormal fetal cTnT levels (p < 0.0001, F(2.86) = 63.5, R = 0.7722). Conclusion: DV-PIV was significantly correlated with fetal cTnT concentrations at delivery. AREDV and abnormal DV flow represent severe cardiac compromise, with increased systemic venous pressure, and a rise in right ventricular afterload, demonstrated by myocardial damage and elevated fetal cTnT. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Idiopathic spinal epidural hematoma in patients with sudden paraplegia: A case report

Introduction. Spontaneous spinal epidural hematoma (SEH) represents 0.3-0.9% of spinal epidural space-occupying lesions, and most surgeons advocate aggressive and early surgical intervention. In. this paper we describe a patient with SEH with sudden paraplegia. Case report. This 30-year-old man had experienced one prior episode of sudden dorsal pain two days before the current admission and while he waited medical attendance, his legs suddenly became weak, and immediately afterwards, he became completely paraplegic in minutes. The patient had complete paraplegia, analgesia below the T4 level and urinary retention. He had no anticoagulant agent and no coagulopathic disease. He was submitted to computerized tomography that demonstrated a dorsally located epidural hematoma extending from the T3 to the T6 level with spinal cord compression. A laminectomy from T3 to T7 was performed four hours after the onset of the symptom. In postoperative time the patient presented the partial sensorial recovery and motor force grade II. The patient was directed to a neurorehabilitation program and in the last medical evaluation he presented recovery for motor grade III-IV without pain. Conclusion. The SHE is rare, with severe neurological consequences for patients and early surgical treatment persist as essential for motor recovery.

Trigonal injection of botulinum toxin-A does not cause vesicoureteral reflux in neurogenic patients

Aims: We evaluated the effect of botulinum toxin type A (BTX-A) injections in the trigone on the antireflux mechanism and evaluated its short-term efficacy. Materials and Methods: Between April and December 2006, 21 patients (10 men and 11 women) were prospectively evaluated. All were incontinent due to refractory NDO and underwent detrusor injection of 300 units of BTX-A, including 50 units into the trigone. Baseline and postoperative evaluation after eight weeks included cystogram, urinary tract ultrasound and urodynamics. Results: At baseline, 20 patients had no vesicoureteral (VUR) and one had grade II unilateral VUR. Postoperative evaluation revealed no cases of de novo VUR and the patient with preinjection VUR had complete resolution of the reflux. Ultrasound showed 5 (23.8%) patients with hydronephrosis before BTX-A injection and only one (4.8%) at the followup evaluation (p=0.066). After treatment, 9 (42.8%) patients became dry, 11 (52.4%) were improved and one (4.8%) had no improvement. Improved patients received antimuscarinic treatment and 8 (38.1%) became dry, with a final total continence rate of 80.1%. Cystometric capacity increased from 271 +/- 92 to 390 +/- 1189 ml (p = 0.002), reflex volume varied from 241 +/- 96 to 323 +/- 201 ml (p = 0.020) and maximum detrusor pressure reduced from 66 +/- 39 to 38 +/- 37 cm H2O (p < 0.001). Conclusions: Our results confirm the safety of trigone injections of BTX-A in terms of development of VUR and upper urinary tract damage. Whether they are beneficial for patients with NDO or other causes of voiding dysfunction will need further studies.