Collagen V and vascular injury promote lung architectural changes in systemic sclerosis

Background: Systemic sclerosis (SSc) is a multisystem disorder characterized by inflammation, fibrosis and vascular damage. The aim of this study was to evaluate the interactions between basement membrane disruption, endothelial injury and collagen V deposition on the vascular wall, as well as their association with pulmonary function tests in patients with SSc. Method: The endothelial apoptosis was assessed by TUNEL and electron microscopy, and quantified through the point-counting technique. To evaluate basement membrane integrity, laminin immunostaining and electron microscopy were used. Immunofluorescence and morphometric analysis were used to determine the amount of collagen V in the vascular walls in 23 open lung biopsies of patients with SSc without pulmonary hypertension. Normal lung tissue was obtained from five individuals who had died of traumatic injuries. Results: The apoptosis index in SSc was higher in the endothelial cells (13.83 +/- 6.83) when compared with the control (2.51 +/- 2.06) group (P < 0.001) and confirmed by electron microscopy. We observed an important disruption of the basement membrane on the vascular wall shown by discontinuous laminin immunostaining and electron microscopy. An increase in collagen V on the vascular wall of the SSc group was observed (45.28 +/- 13.21), when compared with control group (22.90 +/- 4.13, P < 0.001), and this difference was statistically significant. An inverse correlation was found between vital capacity, forced vital capacity, forced expiratory volume in 1 s, vascular collagen V and endothelial apoptosis (P < 0.05). Conclusions: We conclude that the endothelial apoptosis and vascular collagen V interaction reinforce the vascular pathway in the SSc pathogenesis. Further studies are needed to determine whether this relationship is causal or consequential. Please cite this paper as: Parra ER, Aguiar AC Jr, Teodoro WR, de Souza R, Yoshinari NH and Capelozzi VL. Collagen V and vascular injury promote lung architectural changes in systemic sclerosis. The Clinical Respiratory Journal 2009; 3: 135-142.

One-dimensional point interaction with three complex parameters

For a pair of non-Hermitian Hamiltonian H and its Hermitian adjoint H(dagger), there are situations in which their eigenfunctions form a biorthogonal system. We illustrate such a situation by means of a one-particle system with a one-dimensional point interaction in the form of the Fermi pseudo-potential. The interaction consists of three terms with three strength parameters g(i) (i = 1, 2 and 3), which are all complex. This complex point interaction is neither Hermitian nor PT-invariant in general. The S-matrix for the transmission reflection problem constructed with H (or with H(dagger)) in the usual manner is not unitary, but it conforms to the pseudo-unitarity that we define. The pseudounitarity is closely related to the biorthogonality of the eigenfunctions. The eigenvalue spectrum of H with the complex interaction is generally complex but there are cases where the spectrum is real. In such a case H and H(dagger) form a pseudo-Hermitian pair.

Oral tolerance attenuates changes in in vitro lung tissue mechanics and extracellular matrix remodeling induced by chronic allergic inflammation in guinea pigs

Oral tolerance attenuates changes in in vitro lung tissue mechanics and extracellular matrix remodeling induced by chronic allergic inflammation in guinea pigs. J Appl Physiol 104: 1778-1785, 2008. First published April 3, 2008; doi:10.1152/japplphysiol.00830.2007.-Recent studies emphasize the presence of alveolar tissue inflammation in asthma. Immunotherapy has been considered a possible therapeutic strategy for asthma, and its effect on lung tissue had not been previously investigated. Measurements of lung tissue resistance and elastance were obtained before and after both ovalbumin and acetylcholine challenges. Using morphometry, we assessed eosinophil and smooth muscle cell density, as well as collagen and elastic fiber content, in lung tissue from guinea pigs with chronic pulmonary allergic inflammation. Animals received seven inhalations of ovalbumin (1-5 mg/ml; OVA group) or saline (SAL group) during 4 wk. Oral tolerance (OT) was induced by offering ad libitum ovalbumin 2% in sterile drinking water starting with the 1st inhalation (OT1 group) or after the 4th (OT2 group). The ovalbumin-exposed animals presented an increase in baseline and in postchallenge resistance and elastance related to baseline, eosinophil density, and collagen and elastic fiber content in lung tissue compared with controls. Baseline and post-ovalbumin and acetylcholine elastance and resistance, eosinophil density, and collagen and elastic fiber content were attenuated in OT1 and OT2 groups compared with the OVA group. Our results show that inducing oral tolerance attenuates lung tissue mechanics, as well as eosinophilic inflammation and extracellular matrix remodeling induced by chronic inflammation.

Changes in plasma free fatty acid levels in septic patients are associated with cardiac damage and reduction in heart rate variability

Free fatty acids (FFAs) have been shown to produce alteration of heart rate variability (HRV) in healthy and diabetic individuals. Changes in HRV have been described in septic patients and in those with hyperglycemia and elevated plasma FFA levels. We studied if sepsis-induced heart damage and HRV alteration are associated with plasma FFA levels in patients. Thirty-one patients with sepsis were included. The patients were divided into two groups: survivors(n = 12) and nonsurvivors (n = 19). The following associations were investigated: (a) troponin I elevation and HRV reduction and (b) clinical evolution and HRV index, plasma troponin, and plasma FFA levels. Initial measurements of C-reactive protein and gravity Acute Physiology and Chronic Health Evaluation scores were similar in both groups. Overall, an increase in plasma troponin level was related to increased mortality risk. From the first day of study, the nonsurvivor group presented a reduced left ventricular stroke work systolic index and a reduced low frequency (LF) that is one of HRV indexes. The correlation coefficient for LF values and troponin was r(2) = 0.75 (P < 0.05). All patients presented elevated plasma FFA levels on the first day of the study (5.11 +/- 0.53 mg/mL), and this elevation was even greater in the nonsurvivor group compared with the survivors (6.88 +/- 0.13 vs. 3.85 +/- 0.48 mg/mL, respectively; P < 0.05). Cardiac damage was confirmed by measurement of plasma troponin I and histological analysis. Heart dysfunction was determined by left ventricular stroke work systolic index and HRV index in nonsurvivor patients. A relationship was found between plasma FFA levels, LFnu index, troponin levels, and histological changes. Plasma FFA levels emerged as possible cause of heart damage in sepsis.

Chronic nasal instillation of residual-oil fly ash (ROFA) induces brain lipid peroxidation and behavioral changes in rats

Several epidemiological studies have linked particulate matter exposure to numerous adverse health effects on the respiratory, cardiovascular, and reproductive systems (Braga et al., 1999; Zanobetti et al., 2000; Anderson et al., 2001; Farhat et al., 2005). More recently, ambient levels of black carbon were associated to impaired cognitive function in children (Suglia et al., 2008), suggesting that the central nervous system (CNS) may be a target of air pollutants. The present study was conducted to (a) determine whether chronic residual oil fly ash (ROFA) exposure promotes behavioral changes and lipid peroxidation in rat brain areas, and (b) determine whether N-acetylcysteine (NAC), a general antioxidant, prevents these effects. Forty-five-day-old male Wistar rats were exposed or not to ROFA by intranasal instillation and were treated or not with NAC (150 mg/kg) ip for 30 days. One day later, rats were submitted to the open field test to evaluate the motor/exploratory activities and emotionality followed by decapitation. Striatum and cerebellum were dissected to determine lipid peroxidation by the accumulation of thiobarbituric acid-reactive substances (TBARS). ROFA instillation induced an increase in lipid peroxidation level in striatum (p = .033) and cerebellum (p = .030), as compared with the control group. NAC treatment blocked these changes. ROFA promoted a decrease in the frequency of peripheral walking (p = .006) and a decrease in exploration (p = .001), which were not blocked by N-acetylcysteine. The present study provides evidence that toxic particles, administered by the respiratory route, induce oxidative stress in structures of the central nervous system, as well as behavioral alterations. The administration of NAC reduces lipid peroxidation at the striatum and cerebellum levels, but does not influence behavioral disturbances.

Low temperature induced changes in activity and protein levels of the enzymes associated to conversion of starch to sucrose in banana fruit

Storage at low temperature is the most frequently used method to extend the shelf life of banana fruit, and is fundamental for extended storage and transport over long distances. However, storage and transport conditions must be carefully controlled because of the high susceptibility of many commercial cultivars to chilling injury. The physiological behavior of bananas at low temperatures has been studied to identify possible mechanisms of resistance to chilling injury. The aim of this work was to evaluate differences in the starch-to-sucrose metabolism of a less tolerant and susceptible (Musa acuminata, AAA cv. Nanicao) and a more tolerant (M. acuminata x Musa balbusiana, AAB, cv. Prata) banana cultivar to chilling injury. Fruits of these cultivars were stored in chambers at 13 degrees C for 15 d, at which point they were transferred to 19 degrees C, where they were left until complete ripening. The low temperature induced significant changes in the metabolism of starch and sucrose in comparison to fruit ripened only at 19 degrees C. The sucrose accumulation was slightly higher in cv. Prata, and different patterns of starch degradation, sucrose synthesis, activity and protein levels of the alpha-and beta-amylases, starch phosphorylase, sucrose synthase and sucrose phosphate synthase were detected between the cultivars. Our results suggest that starch-to-sucrose metabolism is likely part of the mechanism for cold acclimation in banana fruit, and the cultivar-dependent differences contribute to their ability to tolerate cold temperatures. (C) 2011 Elsevier B.V. All rights reserved.

Rapid antidepressant changes with sleep deprivation in major depressive disorder are associated with changes in vascular endothelial growth factor (VEGF): A pilot study

While conventional antidepressants benefit many patients with major depressive disorder (MDD), as much as eight to 12 weeks can elapse before significant improvements in depressive symptoms are seen. Treatments that act more rapidly in MDD are urgently needed. Sleep deprivation (SD) has been shown to produce a rapid antidepressant response within one day in 50-60% of patients with MDD; thus, identifying its antidepressant mechanism may contribute to the development of antidepressants that act more rapidly. The present study evaluated the effects of 39 h of SD on mood, as well as on plasma levels of brain derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) in patients with MDD. After a drug-free period of at least two weeks, 11 patients (6 males, 5 females; ages 25-62) who met DSM-IV criteria for MDD underwent total SD. Plasma samples for BDNF and VEGF assays were collected on Days 1 (baseline) and 2. The six-item Hamilton Rating Scale for Depression (HAMD-6) was the primary outcome measure. HAMD-6 scores decreased significantly after SD (Day 2). SD was negatively correlated with change in HAMD-6 score and change in VEGF levels, indicating that as depression scores decreased following SD, VEGF plasma levels increased. In contrast, SD did not alter plasma BDNF concentrations, nor was an association found between BDNF levels and clinical improvement on the HAMD-6. These results suggest that SD is associated with mood-related changes in plasma VEGF levels, but not plasma BDNF levels. Further studies using larger sample sizes are needed to confirm these preliminary findings. Published by Elsevier Inc.

Changes in Management Strategies After Spontaneous Migration of a Retained Intraorbital Metallic Foreign Body

Purpose: Because of the controversial biologic tolerance and management, retained intraorbital metallic foreign body (RIMFb) poses a formidable challenge to surgeons. Besides location of the foreign body, indications for surgical management include neurologic injury, mechanical restriction of the eye movement, and development of local infection or draining fistula. The authors describe an unusual case of spontaneous migration of a RIMFb. Methods: A 26-year-old man had a gunshot injury on the left orbit. The patient was initially managed conservatively because of the posterior position of the bullet fragment. Thereafter, because of the clinical impairments and anterior migration of projectile, surgical treatment was considered. Results: Spontaneous anterior migration has led to mechanical disturbances and inflammatory complications that comprise explicit surgical indications for removal. The patient underwent surgery with complete relief of symptoms. We suppose that extrinsic ocular muscles might play a role in shifting large RIMFb over time, leading to change in the management strategies. Conclusions: Spontaneous migration of RIMFb is a rare clinical situation that can lead to pain, local deformity, as well as changes in the management strategies of the affected patients even in the late phase of follow-up.

Variation in Body Composition Determines Long-Term Blood Pressure Changes in Pre-Hypertension The MONICA/KORA (Monitoring Trends and Determinants on Cardiovascular Diseases/Cooperative Research in the Region of Augsburg) Cohort Study

Objectives We studied the relationship between changes in body composition and changes in blood pressure levels. Background The mechanisms underlying the frequently observed progression from pre-hypertension to hypertension are poorly understood. Methods We examined 1,145 subjects from a population-based survey at baseline in 1994/1995 and at follow-up in 2004/2005. First, we studied individuals pre-hypertensive at baseline who, during 10 years of follow-up, either had normalized blood pressure (PreNorm, n = 48), persistently had pre-hypertension (PrePre, n = 134), or showed progression to hypertension (PreHyp, n = 183). In parallel, we studied predictors for changes in blood pressure category in individuals hypertensive at baseline (n = 429). Results After 10 years, the PreHyp group was characterized by a marked increase in body weight (+5.71% [95% confidence interval (CI): 4.60% to 6.83%]) that was largely the result of an increase in fat mass (+17.8% [95% CI: 14.5% to 21.0%]). In the PrePre group, both the increases in body weight (+1.95% [95% CI: 0.68% to 3.22%]) and fat mass (+8.09% [95% CI: 4.42% to 11.7%]) were significantly less pronounced than in the PreHyp group (p < 0.001 for both). The PreNorm group showed no significant change in body weight (-1.55% [95% CI: -3.70% to 0.61%]) and fat mass (+0.20% [95% CI: -6.13% to 6.52%], p < 0.05 for both, vs. the PrePre group). Conclusions After 10 years of follow-up, hypertension developed in 50.1% of individuals with pre-hypertension and only 6.76% went from hypertensive to pre-hypertensive blood pressure levels. An increase in body weight and fat mass was a risk factor for the development of sustained hypertension, whereas a decrease was predictive of a decrease in blood pressure. (J Am Coll Cardiol 2010; 56: 65-76) (C) 2010 by the American College of Cardiology Foundation

Changes in Perfusion-Weighted Magnetic Resonance Imaging after Carotid Angioplasty with Stent

Carotid artery stenosis due to arteriosclerosis increases the risk of cerebral ischemia via embolic phenomena or reduced blood flow. The changes in cerebral perfusion that may occur after treatment are not clearly understood. This study evaluated the changes in cerebral microcirculation following carotid angioplasty with stenting (CAS) under cerebral protection with filters using ultrafast gradient echo (GRE) perfusion weighted imaging (PWI) with magnetic resonance imaging (MRI). Prospectively, 21 cervical carotid stenosis patients, mean age 69.95 years, underwent MRI 12 h before and 72 h after CAS. PWI parameters were collected for statistical analysis: cerebral blood volume (CB V), mean transit time (MTT) and time to peak (TTP). Statistical analysis was applied to absolute parameters and to values normalized against those from the contralateral parenchyma. The main finding of this study was improved hemodynamics for the normalized data after CAS, shown by reduced MTT (p<0.001) and TTP (p=0.019) in the territory fed by the middle cerebral artery ipsilateral to the CAS. Absolute data showed increased blood volume in the cerebral hemispheres after CAS, which was more accentuated on the stent side (p=0.016) than the contralateral side (p=0.029). Early improvements in cerebral perfusion, mainly seen in the normalized data, were clearly demonstrated in the timing parameters - TTP & MTT - after CAS.

Changes of somatomotor and parietal regions produced by different amounts of electrical stimulation

Our study aims to investigate changes in electrocortical activity by observing the variations in absolute theta power in the primary somatomotor and parietal regions of the brain under three different electrical stimulation conditions: control group (without stimulation), group 24 (24 trials of stimulation) and group 36 (36 trials of stimulation). Thus, our hypothesis is that the application of different patterns of electrical stimulation will promote different states of habituation in these regions. The sample was composed of 24 healthy (absence of mental and physical impairments) students (14 male and 10 female), with ages varying from 25 to 40 years old (32.5 +/- 7.5), who are right-handed (Edinburgh Inventory). The subjects were randomly distributed into three groups: control (n = 8), G24 (n = 8) and G36 (n = 8). We use the Functional electrical stimulation (FES) equipment (NeuroCompact-2462) to stimulate the right index finger extensor muscle, while the electroencephalographic signal was simultaneously recorded. We found an interaction between condition and block factors for the C3 and P3 electrode, a condition and block main effects for the C4 electrode, and a condition main effect for the P4 electrode. Our results support the hypothesis that electrical stimulation promotes neurophysiological changes. It appears that stimulus adaptation (accommodation) of specific circuits can strengthen the brain`s ability to distinguish between and respond to such stimuli over time. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Changes in Cell Wall Composition Associated to the Softening of Ripening Papaya: Evidence of Extensive Solubilization of Large Molecular Mass Galactouronides

Papaya (Carica papaya) is a climacteric fruit that undergoes dramatic pulp softening. Fruits sampled at three different conditions (natural ripening or after exposition to ethylene or 1-methylcyclopropene) were used for the isolation of cell wall polymers to find changes in their degradation pattern. Polymers were separated according to their solubility in water, CDTA, and 4 M alkali, and their monosaccharide compositions were determined. Water-soluble polymers were further characterized, and their increased yields in control and ethylene-treated fruit, in contrast to those that were treated with 1-MCP, indicated a strong association between fruit softening and changes in the cell wall water-soluble polysaccharide fraction. The results indicate that the extensive softening in the pulp of ripening papayas is a consequence of solubilization of large molecular mass galacturonans from the pectin fraction of the cell wall. This process seems to be dependent on the levels of ethylene, and it is likely that the releasing of galacturonan chains results from an endo acting polygalacturonase.