Impact of pressure profile and duration of recruitment maneuvers on morphofunctional and biochemical variables in experimental lung injury

Objective: To investigate the effects of the rate of airway pressure increase and duration of recruitment maneuvers on lung function and activation of inflammation, fibrogenesis, and apoptosis in experimental acute lung injury. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: Thirty-five Wistar rats submitted to acute lung injury induced by cecal ligation and puncture. Interventions: After 48 hrs, animals were randomly distributed into five groups (seven animals each): 1) nonrecruited (NR); 2) recruitment maneuvers (RMs) with continuous positive airway pressure (CPAP) for 15 secs (CPAP15); 3) RMs with CPAP for 30 secs (CPAP30); 4) RMs with stepwise increase in airway pressure (STEP) to targeted maximum within 15 secs (STEP15); and 5) RMs with STEP within 30 secs (STEP30). To perform STEP RMs, the ventilator was switched to a CPAP mode and positive end-expiratory pressure level was increased stepwise. At each step, airway pressure was held constant. RMs were targeted to 30 cm H(2)O. Animals were then ventilated for 1 hr with tidal volume of 6 mL/kg and positive end-expiratory pressure of 5 cm H(2)O. Measurements and Main Results: Blood gases, lung mechanics, histology (light and electronic microscopy), interleukin-6, caspase 3, and type 3 procollagen mRNA expressions in lung tissue. All RMs improved oxygenation and lung static elastance and reduced alveolar collapse compared to NR. STEP30 resulted in optimal performance, with: 1) improved lung static elastance vs. NR, CPAP15, and STEP15; 2) reduced alveolar-capillary membrane detachment and type 2 epithelial and endothelial cell injury scores vs. CPAP15 (p < .05); and 3) reduced gene expression of interleukin-6, type 3 procollagen, and caspase 3 in lung tissue vs. other RMs. Conclusions: Longer-duration RMs with slower airway pressure increase efficiently improved lung function, while minimizing the biological impact on lungs. (Crit Care Med 2011; 39:1074-1081)

Similar Intracellular Peptide Profile of TAP1/beta 2 Microglobulin Double-Knockout Mice and C57BL/6 Wild-Type Mice as Revealed by Peptidomic Analysis

Cells produce and use peptides in distinctive ways. In the present report, using isotope labeling plus semi-quantitative mass spectrometry, we evaluated the intracellular peptide profile of TAP1/beta 2m(-/-) (transporter associated with antigen-processing 1/beta 2 microglobulin) double-knockout mice and compared it with that of C57BL/6 wild-type animals. Overall, 92 distinctive peptides were identified, and most were shown to have a similar concentration in both mouse strains. However, some peptides showed a modest increase or decrease (similar to 2-fold), whereas a glycine-rich peptide derived from the C-terminal of neurogranin (KGPGPGGPGGAGGARGGAGGGPSGD) showed a substantial increase (6-fold) in TAP1/beta 2m(-/-) mice. Thus, TAP1 and beta 2microglobulin have a small influence on the peptide profile of neuronal tissue, suggesting that the presence of peptides derived from intracellular proteins in neuronal tissue is not associated with antigens of the class I major histocompatibility complex. Therefore, it is possible that these intracellular peptides play a physiological role.

APOE polymorphism is associated with lipid profile, but not with arterial stiffness in the general population

Background: Cardiovascular diseases (CVD) are the main cause of death and disability in developed countries. In most cases, the progress of CVD is influenced by environmental factors and multifactorial inheritance. The purpose of this study was to investigate the association between APOE genotypes, cardiovascular risk factors, and a noninvasive measure of arterial stiffness in the Brazilian population. Methods: A total of 1493 urban Brazilian individuals were randomly selected from the general population of the Vitoria City Metropolitan area. Genetic analysis of the APOE polymorphism was conducted by PCR-RFLP and pulse wave velocity analyzed with a noninvasive automatic device. Results: Age, gender, body mass index, triglycerides, creatinine, uric acid, blood glucose, blood pressure phenotypes were no different between epsilon 2, epsilon 3 and epsilon 4 alleles. The epsilon 4 allele was associated with higher total-cholesterol (p < 0.001), LDL-C (p < 0.001), total-cholesterol/HDL-C ratio (p < 0.001), LDL/HDL-C ratio (p < 0.001), lower HDL-C values (p < 0.001) and higher risk to obesity (OR = 1.358, 95% CI = 1.019-1.811) and hyperuricemia (OR = 1.748, 95% CI = 1.170-2.611). Nevertheless, pulse wave velocity (p = 0.66) measures were no different between genotypes. The significant association between APOE genotypes and lipid levels persisted after a 5-year follow-up interval, but no interaction between time and genotype was observed for lipids longitudinal behavior. Conclusion: The epsilon 4 allele of the APOE gene is associated with a worse lipid profile in the Brazilian urban population. In our relatively young sample, the observed effect of APOE genotype on lipid levels was not translated into significant effects in arterial wall stiffness.

Demographic profile of blood donors at three major Brazilian blood centers: results from the International REDS-II study, 2007 to 2008

BACKGROUND: The profile of blood donors changed dramatically in Brazil over the past 20 years, from remunerated to nonremunerated and then from replacement to community donors. Donor demographic data from three major blood centers establish current donation profiles in Brazil, serving as baseline for future analyses and tracking longitudinal changes in donor characteristics. STUDY DESIGN AND METHODS: Data were extracted from the blood center, compiled in a data warehouse, and analyzed. Population data were obtained from the Brazilian census. RESULTS: During 2007 to 2008, there were 615,379 blood donations from 410,423 donors. A total of 426,142 (69.2%) were from repeat (Rpt) donors and 189,237 (30.8%) were from first-time (FT) donors. Twenty percent of FT donors returned to donate in the period. FT donors were more likely to be younger, and Rpt donors were more likely to be community donors. All were predominantly male. Replacement donors still represent 50% of FT and 30% of Rpt donors. The mean percentage of the potentially general population who were donors was approximately 1.2% for the three centers (0.7, 1.5, and 3.1%). Adjusting for the catchment`s area, the first two were 2.1 and 1.6%. CONCLUSIONS: Donors in the three Brazilian centers tended to be younger with a higher proportion of males than in the general population. Donation rates were lower than desirable. There were substantial differences in sex, age, and community/replacement status by center. Studies on the safety, donation frequencies, and motivations of donors are in progress to orient efforts to enhance the availability of blood.

Cytokine Profile in Pleural Fluid and Serum After Lung Transplantation

Background. Lung transplantation is the procedure of choice in several end-stage lung diseases. Despite improvements in surgical techniques and immunosuppression, early postoperative complications occur frequently. Objective. To evaluate the pleural inflammatory response after surgery. Patients and Methods. Twenty patients aged 18 to 63 years underwent unilateral or bilateral lung transplantation between August 2006 and March 2008. Proinflammatory cytokines interleukin (IL)-1 beta, IL-6, and IL-8 and vascular endothelial growth factor in pleural fluid and serum were analyzed. For cytokine evaluation, 20-mL samples of pleural fluid and blood (right, left, or both chest cavities) were obtained at 6 hours after surgery and daily until removal of the chest tube or for a maximum of 10 days. Data were analyzed using analysis of variance followed by the Holm-Sidak test. Results. All effusions were exudates according to Light`s criteria. Pleural fluid cytokine concentrations were highest at 6 hours after surgery. Serum concentrations were lower than those in pleural fluid, and IL-1 beta, IL-6, and IL-8 were undetectable at all time points. Conclusions. There is a peak concentration of inflammatory cytokines in the first 6 hours after transplantation, probably reflecting the effects of surgical manipulation. The decrease observed from postoperative day 1 and thereafter suggests the action of the immunosuppression agents and a temporal reduction in pleural inflammation.

Erection induced by Tx2-6 toxin of Phoneutria nigriventer spider: Expression profile of genes in the nitric oxide pathway of penile tissue of mice

The peptides Tx2-5 and Tx2-6, isolated from the whole venom of ""armed-spider"" Phoneutria nigniventer venom, are directly linked with the induction of persistent and painful erection in the penis of mammals. The erection induced by Tx2-6 has been associated with the activation of nitric oxide synthases. There is a scarcity of studies focusing on the outcome of Tx2-6 at the molecular level, by this reason we evaluated the gene profile activity of this toxin at the nitric oxide (NO) pathway. After microarray analyses on cavernous tissue of mice inoculated with Tx2-6 we found that only 10.4% (10/96) of these genes were differentially expressed, showing a limited effect of the toxin on the NO pathway. We found the genes sparc, ednrb, junb, cdkn1a, bcl2, ccl5, abcc1 over-expressed and the genes sod1, s100a10 and fth1 under-expressed after inoculation of Tx2-6. The differential expressions of sparc and ednrb genes were further confirmed using real-time PCR. Interestingly, ednrb activates the L-arginine/NO/cGMP pathway that is involved in the relaxation of the cavernous body. Therefore the priapism induced by Tx2-6 is a consequence of a highly specific interference of this neurotoxin with the NO pathway. (C) 2009 Elsevier Ltd. All rights reserved.

Novel humanized anti-CD3 antibodies induce a predominantly immunoregulatory profile in human peripheral blood mononuclear cells

Strategies to minimize the immunogenicity and toxicity of murine anti-CD3 antibodies (e.g. OKT3) are of special interest for organ transplantation and for the treatment of autoimmune diseases. In the present work, we have developed two humanized anti-CD3 antibodies. These molecules were shown to bind to human CD3, though less efficiently, and display less mitogenic activity than CKT3. These results prompted us to investigate whether this reduced mitogenic potential was associated with the development of anti-inflammatory properties. Indeed, in peripheral blood mononuclear cells (PBMCs), the humanized antibody versions induced a predominantly anti-inflammatory cytokine profile, in contrast with the pro-inflammatory profile induced by OKT3. Neither OKT3 nor the humanized versions induced the expression of IL-4, IL-2 or TGF-beta. Both humanized antibodies induced significantly lower production of IFN-gamma and IL-5 and slightly higher production of IL-10 than OKT3. This immunomodulatory profile was most evident by the 80-fold higher ratio of IL-10/IFN-gamma production in PBMCs cultured in the presence of the humanized antibodies, compared to those stimulated with CKT3. Furthermore, these humanized anti-CD3 antibodies induced a late FOXP3 gene expression while OKT3 led to a more transient expression of FOXP3. Taken our results, we suggest that these humanized anti-CD3 antibodies may promote the development of T cells with immunoregulatory activity. (C) 2009 Elsevier B.V. All rights reserved.

Safety Profile of Trocar and Insufflation Needle Access Systems in Laparoscopic Surgery

BACKGROUND: The most common laparoscopic complications are associated with trocar insertion. The purpose of this study was to develop an objective method of evaluating the safety profile of various access devices used in laparoscopic surgery. STUDY DESIGN: In 20 swine, 6 bladed and 2 needle access devices were evaluated. A force profile was determined by measuring the force required to drive the trocar or needle through the fascia and into the peritoneum, at 0 and 10 mmHg. The amount Of tissue deformation, the length of blade exposed, and the duration of exposure were measured using a high-speed digital imaging system. RESULTS: The needle system without the sheath required the least driving force and had the most favorable force profile. In contrast, the bladed, nonretractable trocar system required a higher driving force and a rapid loss of resistance. Insertion under a pneumoperitoneum did not significantly alter the force profile of the various access devices except for the amount of tissue deformation. With the bladed system, the blade itself was exposed for an average of 0.5 to 1.0 seconds for a distance of 4.5 to 5.0 cm. In comparison, the needle system was exposed for 0.2 seconds for a distance of 1.8 cm. CONCLUSIONS: We developed a reproducible method of measuring the forces required to place the access systems, their pattern of resistance loss, and the characteristics of the blade exposure. These parameters may provide an adjunctive and objective measurement of safety, allowing for more direct comparison between various trocar designs. (J Am Coll Surg 2009;209:222-232. (C) 2009 by the American College of Surgeons)

Neuropsychological Profile of Brazilian Older Adults with Heterogeneous Educational Backgrounds

Education significantly impacts cognitive performance of older adults even in the absence of dementia. Some cognitive tests seem less vulnerable to the influence of education and thus may be more suitable for cognitive assessment of older adults with heterogeneous backgrounds. The objective of this study was to investigate which tests in a cognitive battery were less influenced by educational levels in a sample of cognitively unimpaired older Brazilians. In addition, we evaluated the impact of very high educational levels on cognitive performance. The cognitive battery consisted of the Mini Mental State Examination (MMSE), Cambridge Cognitive Test (CAMCOG), Clock Drawing Test, Short Cognitive Performance Test (SKT), Rivermead Behavioural Memory Test (RBMT), Fuld Object Memory Evaluation (FOME), Verbal Fluency Test (VF) fruit category, Trail Making Test A and B, WAIS-R Vocabulary, and Block Design. Education did not exert a significant influence on the RBMT, FOME, and VF (p < .05). Subjects with very high educational levels had similar performance on the latter tests when compared with those with intermediate and low levels of education. In conclusion, the RBMT, FOME, and VF fruit category seem to be appropriate tools for the assessment of cognitive function in elderly Brazilians with varying degrees of educational attainment.

Nutritional recommendation alone does not change the obesity profile of health professionals

Objective: To evaluate the frequency of overweight and obesity in health professionals, before and after a single specialized dietary recommendation. Methods: Anthropometric measures of 579 workers of a general hospital in the city of Sao Paulo, Brazil were taken. The weight (f), height (h) and waist circumference (wc) were interpreted according to the WHO and NCEP ATP III guidelines. Nutrition specialist provided dietary and behavioral recommendations. The entire sample underwent a new evaluation one year later. Results: At the first evaluation, 79 employees presente WC >= 102 cm (male) or WC >= 88 cm (female). The association between WC >= 102 cm (men) or WC >= 88 cm (women) and BMI >= 30 kg/m(2) was found in 12.8 % (69 subjects). The BMI distribution per age group indicated that the increase in overweight and obesity was directly proportional to the age increase. Physical activities were not practiced by 75% of the subjects studied. A year later, the evaluation indicated lack of statistical differences regarding the BMI and waist circumference of the sample and only 2.8% started to practice a physical activity. Conclusion: Dietary recommendation alone failed to promote changes in the eating habits of health professionals who work at a general hospital or to encourage them to practice exercise.

Idiopathic Toe Walking A Kinematic and Kinetic Profile

Purpose: The differential diagnosis in children who walk on their toes includes mild spastic diplegia and idiopathic toe walking (ITW). A diagnosis of ITW is often one of exclusion. To better characterize the diagnosis of ITW, quantitative gait analysis was utilized in a series of patients with an established diagnosis of ITW. Study Design: Patients with an established diagnosis of ITW were analyzed by quantitative gait analysis. Data were recorded as each subject walked in a self-selected toe-walking pattern. The subject was then asked to ambulate making every effort to walk in a normal heel-toe reciprocating fashion. Data were collected to determine if this group of idiopathic toe walkers was able to normalize their gait. Data sets were compared with each other and with historical normal controls. Results: Fifty-one neurologically normal children ( 102 extremities) with ITW were studied in the Motion Analysis Laboratory at a mean age of 9.3 years. In the self-selected trials, significant deviations in both kinematics and kinetics at the level of the ankle were identified. Disruption of all 3 ankle rockers and a plantar flexion bias of the ankle throughout the gait cycle were most commonly seen. When asked to attempt a normal heel-toe gait, 17% of the children were able to normalize both stance and swing variables. In addition, 70% were able to normalize some but not all of the stance and swing variables. Conclusion: Quantitative gait analysis is an effective tool for differentiating mild cerebral palsy from ITW. Kinematic and kinetic distinctions between the diagnoses are evident at the knee and ankle. The ability to normalize on demand at least some of the kinematic and kinetic variables associated with toe walking is seen in most children with ITW.

Frequency and clinical profile of patients with polycystic kidney disease in Southern Brazil

Background. Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common genetic nephropathies, affecting one in every 800-1000 individuals in the worldwide general population and 5-10% of hemodialysis patients. Little data concerning the prevalence of ADPKD in Brazil are available. Thus, the aim of the present study was to investigate both the frequency and clinical profile of ADPKD among hemodialysis patients in south of Brazil. Methods. This cross-sectional study consisted of patients from 24 hemodialysis centers. Patients were screened for ADPKD by clinical, laboratorial, and image examination in medical records. Results. Of 1326 patients on hemodialysis in the south of Brazil that composed this study, 99 (7.5%) had polycystic kidney as primary cause for chronic renal failure. Comparisons between ADPKD and non-ADPKD patients revealed no differences regarding mean age, gender, and ethnicity. Conclusions. Our data revealed that ADPKD is prevalent among patients on hemodialysis in the south of Brazil. In addition, the clinical profile of ADPKD is similar to reported data from North America and Europe, putatively due to the similar ethnic composition mainly based on European descents.

In Vivo Effects of Bothrops jararaca Venom on Metabolic Profile and on Muscle Protein Metabolism in Rats

This study investigated the in vivo effects of the Bothrops Jararaca venom (BjV) on general metabolic profile and, specifically. oil muscle protein metabolism in rats. The crude venom (0.4 mg/kg body weight, IV) was infused in awake rats, and plasma activity of enzymes and metabolites levels were determined after 1, 2, 3, and 4 hours. BjV increased urea, lactate, and activities of creatine kinase. lactate dehydrogenase. and aspartate aminotransferase after 4 hours. The content of liver glycogen was reduced by BjV. Protein metabolism was evaluated by means of microdialysis technique and in isolated muscles. BjV induced increase in the muscle interstitial-arterial tyrosine concentration difference. indicating a high protein catabolism. The myotoxicity induced by this venom is associated with reduction of protein synthesis and increase in rates of overall proteolysis, which was accompanied by activation of lysosomal and ubiquitin-proteasome systems without changes in protein levels of cathepsins and ubiquitin-protein conjugates.

Gene expression profile analysis of primary glioblastomas and non-neoplastic brain tissue: identification of potential target genes by oligonucleotide microarray and real-time quantitative PCR

The prognosis of glioblastomas is still extremely poor and the discovery of novel molecular therapeutic targets can be important to optimize treatment strategies. Gene expression analyses comparing normal and neoplastic tissues have been used to identify genes associated with tumorigenesis and potential therapeutic targets. We have used this approach to identify differentially expressed genes between primary glioblastomas and non-neoplastic brain tissues. We selected 20 overexpressed genes related to cell cycle, cellular movement and growth, proliferation and cell-to-cell signaling and analyzed their expression levels by real time quantitative PCR in cDNA obtained from microdissected fresh tumor tissue from 20 patients with primary glioblastomas and from 10 samples of non-neoplastic white matter tissue. The gene expression levels were significantly higher in glioblastomas than in non-neoplastic white matter in 18 out of 20 genes analyzed: P < 0.00001 for CDKN2C, CKS2, EEF1A1, EMP3, PDPN, BNIP2, CA12, CD34, CDC42EP4, PPIE, SNAI2, GDF15 and MMP23b; and NFIA (P: 0.0001), GPS1 (P: 0.0003), LAMA1 (P: 0.002), STIM1 (P: 0.006), and TASP1 (P: 0.01). Five of these genes are located in contiguous loci at 1p31-36 and 2 at 17q24-25 and 8 of them encode surface membrane proteins. PDPN and CD34 protein expression were evaluated by immunohistochemistry and they showed concordance with the PCR results. The present results indicate the presence of 18 overexpressed genes in human primary glioblastomas that may play a significant role in the pathogenesis of these tumors and that deserve further functional investigation as attractive candidates for new therapeutic targets.