Gisele Pinto de Oliveira

Intravenous glutamine decreases lung and distal organ injury in an experimental model of abdominal sepsis

IntroductionThe protective effect of glutamine, as a pharmacological agent against lung injury, has been reported in experimental sepsis; however, its efficacy at improving oxygenation and lung mechanics, attenuating diaphragm and distal organ injury has to be better elucidated. In the present study, we tested the hypothesis that a single early intravenous dose of glutamine was associated not only with the improvement of lung morpho-function, but also the reduction of the inflammatory process and epithelial cell apoptosis in kidney, liver, and intestine villi.MethodsSeventy-two Wistar rats were randomly assigned into four groups. Sepsis was induced by cecal ligation and puncture surgery (CLP), while a sham operated group was used as control (C). One hour after surgery, C and CLP groups were further randomized into subgroups receiving intravenous saline (1 ml, SAL) or glutamine (0.75 g/kg, Gln). At 48 hours, animals were anesthetized, and the following parameters were measured: arterial oxygenation, pulmonary mechanics, and diaphragm, lung, kidney, liver, and small intestine villi histology. At 18 and 48 hours, Cytokine-Induced Neutrophil Chemoattractant (CINC)-1, interleukin (IL)-6 and 10 were quantified in bronchoalveolar and peritoneal lavage fluids (BALF and PLF, respectively).ResultsCLP induced: a) deterioration of lung mechanics and gas exchange; b) ultrastructural changes of lung parenchyma and diaphragm; and c) lung and distal organ epithelial cell apoptosis. Glutamine improved survival rate, oxygenation and lung mechanics, minimized pulmonary and diaphragmatic changes, attenuating lung and distal organ epithelial cell apoptosis. Glutamine increased IL-10 in peritoneal lavage fluid at 18 hours and bronchoalveolar lavage fluid at 48 hours, but decreased CINC-1 and IL-6 in BALF and PLF only at 18 hours.ConclusionsIn an experimental model of abdominal sepsis, a single intravenous dose of glutamine administered after sepsis induction may modulate the inflammatory process reducing not only the risk of lung injury, but also distal organ impairment. These results suggest that intravenous glutamine may be a potentially beneficial therapy for abdominal sepsis.

Tuberculosis in Brazil: last ten years analysis – 2001–2010

OBJECTIVE To describe tuberculosis epidemiological situation in Brazil, as well as program performance indicators in 2001-2010 period, and discuss the relationship between changes observed and control measures implemented in this century first decade. METHODS It is a descriptive study, data source was the Information System for Notifiable Diseases (Sinan), Mortality Information System (SIM), Unified Health System Hospital Information System (SIH/SUS) and TB Multidrug-resistant Surveillance System (MDR-TB/SS). Indicators analyzed were organized into four major groups: TB control program (TCP) coverage and case detection; morbidity; treatment and TCP performance; and mortality. RESULTS In the years analyzed there was a decrease in the number of new cases and incidence rate, mortality reduction (relative and absolute), and improvement in TB detection and diagnosis, as well in TB/HIV coinfection and drug resistance. However, little progress was found in contact investigation, diagnosis in primary care and TB cure rate. DISCUSSION Results showed many advances in tuberculosis control in the 10 years analyzed, but it also points to serious obstacles that need to be solved so Brazil can eliminate tuberculosis as a public health problem.

Hypervolemia induces and potentiates lung damage after recruitment maneuver in a model of sepsis-induced acute lung injury

IntroductionRecruitment maneuvers (RMs) seem to be more effective in extrapulmonary acute lung injury (ALI), caused mainly by sepsis, than in pulmonary ALI. Nevertheless, the maintenance of adequate volemic status is particularly challenging in sepsis. Since the interaction between volemic status and RMs is not well established, we investigated the effects of RMs on lung and distal organs in the presence of hypovolemia, normovolemia, and hypervolemia in a model of extrapulmonary lung injury induced by sepsis.MethodsALI was induced by cecal ligation and puncture surgery in 66 Wistar rats. After 48 h, animals were anesthetized, mechanically ventilated and randomly assigned to 3 volemic status (n = 22/group): 1) hypovolemia induced by blood drainage at mean arterial pressure (MAP)≈70 mmHg; 2) normovolemia (MAP≈100 mmHg), and 3) hypervolemia with colloid administration to achieve a MAP≈130 mmHg. In each group, animals were further randomized to be recruited (CPAP = 40 cm H2O for 40 s) or not (NR) (n = 11/group), followed by 1 h of protective mechanical ventilation. Echocardiography, arterial blood gases, static lung elastance (Est,L), histology (light and electron microscopy), lung wet-to-dry (W/D) ratio, interleukin (IL)-6, IL-1β, caspase-3, type III procollagen (PCIII), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) mRNA expressions in lung tissue, as well as lung and distal organ epithelial cell apoptosis were analyzed.ResultsWe observed that: 1) hypervolemia increased lung W/D ratio with impairment of oxygenation and Est,L, and was associated with alveolar and endothelial cell damage and increased IL-6, VCAM-1, and ICAM-1 mRNA expressions; and 2) RM reduced alveolar collapse independent of volemic status. In hypervolemic animals, RM improved oxygenation above the levels observed with the use of positive-end expiratory pressure (PEEP), but increased lung injury and led to higher inflammatory and fibrogenetic responses.ConclusionsVolemic status should be taken into account during RMs, since in this sepsis-induced ALI model hypervolemia promoted and potentiated lung injury compared to hypo- and normovolemia.

Understanding the mechanisms of glutamine action in critically ill patients

Glutamine (Gln) is an important energy source and has been used as a supplementary energy substrate. Furthermore, Gln is an essential component for numerous metabolic functions, including acid-base homeostasis, gluconeogenesis, nitrogen transport and synthesis of proteins and nucleic acids. Therefore, glutamine plays a significant role in cell homeostasis and organ metabolism. This article aims to review the mechanisms of glutamine action during severe illnesses. In critically ill patients, the increase in mortality was associated with a decreased plasma Gln concentration. During catabolic stress, Gln consumption rate exceeds the supply, and both plasma and skeletal muscle pools of free Gln are severely reduced. The dose and route of Gln administration clearly influence its effectiveness: high-dose parenteral appears to be more beneficial than low-dose enteral administration. Experimental studies reported that Gln may protect cells, tissues, and whole organisms from stress and injury through the following mechanisms: attenuation of NF (nuclear factor)-kB activation, a balance between pro- and anti-inflammatory cytokines, reduction in neutrophil accumulation, improvement in intestinal integrity and immune cell function, and enhanced of heat shock protein expression. In conclusion, high-doses of parenteral Gln (>0.50 g/kg/day) demonstrate a greater potential to benefit in critically ill patients, although Gln pathophysiological mechanisms requires elucidation.

Uso do sistema de informação sobre mortalidade para identificar subnotificação de casos de tuberculose no Brasil

The aim of the study was to analyze the underreporting of deaths from tuberculosis (TB) in Brazil, as well as to assess the impact these cases would cause in the reporting rate and proportion of TB deaths in 2006. We analyzed the deaths recorded in the Mortality Information System (SIM) in 2006 and all reports of TB in Brazil during the 2001 to 2006 period. The variables used for the relationship were: report number, city and State of residence, patient name, date and year of birth, sex, mothers name and address. Six blocking steps were performed. Scores above 12.4 were considered pairs, and those below 9.7, doubtful pairs. After each step, we performed a manual review of doubtful pairs. The Reportable Disease Information System (Sinan) had 547,589 records. The SIM had 6,924 records, 39.3% (n = 2,727) of which were not found in Sinan during the period evaluated. We observed that 64.5% (2,707) of deaths were reported in 2006 and after analyzing the proportion of deaths underreported by region and federal units, we found that the highest percentage was in the Northern region, followed by the Southeast and Northeast. The addition of deaths that had not been reported to the Sinan database increased the reporting rate 3.7%. Regarding the proportion of deaths due to TB, such inclusion was responsible for a 60.7% increase in this indicator. The relationship between both databases seems to be an important strategy for improving the quality of the TB surveillance system.

Regular and moderate exercise before experimental sepsis reduces the risk of lung and distal organ injury

Physical activity modulates inflammation and immune response in both normal and pathologic conditions. We investigated whether regular and moderate exercise before the induction of experimental sepsis reduces the risk of lung and distal organ injury and survival. One hundred twenty-four BALB/c mice were randomly assigned to two groups: sedentary (S) and trained (T). Animals in T group ran on a motorized treadmill, at moderate intensity, 5% grade, 30 min/day, 3 times a week for 8 wk. Cardiac adaptation to exercise was evaluated using echocardiography. Systolic volume and left ventricular mass were increased in T compared with S group. Both T and S groups were further randomized either to sepsis induced by cecal ligation and puncture surgery (CLP) or sham operation (control). After 24 h, lung mechanics and histology, the degree of cell apoptosis in lung, heart, kidney, liver, and small intestine villi, and interleukin (IL)-6, KC (IL-8 murine functional homolog), IL-1β, IL-10, and number of cells in bronchoalveolar lavage (BALF) and peritoneal lavage (PLF) fluids as well as plasma were measured. In CLP, T compared with S groups showed: 1) improvement in survival; 2) reduced lung static elastance, alveolar collapse, collagen and elastic fiber content, number of neutrophils in BALF, PLF, and plasma, as well as lung and distal organ cell apoptosis; and 3) increased IL-10 in BALF and plasma, with reduced IL-6, KC, and IL-1β in PLF. In conclusion, regular and moderate exercise before the induction of sepsis reduced the risk of lung and distal organ damage, thus increasing survival.

Prolonged recruitment manoeuvre improves lung function with less ultrastructural damage in experimental mild acute lung injury

The effects of prolonged recruitment manoeuvre (PRM) were compared with sustained inflation (SI) in paraquat-induced mild acute lung injury (ALI) in rats. Twenty-four hours after ALI induction, rats were anesthetized and mechanically ventilated with VT=6 ml/kg and positive end-expiratory pressure (PEEP)=5 cmH(2)O for 1h. SI was performed with an instantaneous pressure increase of 40 cmH(2)O that was sustained for 40s, while PRM was done by a step-wise increase in positive inspiratory pressure (PIP) of 15-20-25 cmH(2)O above a PEEP of 15 cm H(2)O (maximal PIP=40 cmH(2)O), with interposed periods of PIP=10 cmH(2)O above a PEEP=15 cmH(2)O. Lung static elastance and the amount of alveolar collapse were more reduced with PRM than SI, yielding improved oxygenation. Additionally, tumour necrosis factor-alpha, interleukin-6, interferon-gamma, and type III procollagen mRNA expressions in lung tissue and lung epithelial cell apoptosis decreased more in PRM. In conclusion, PRM improved lung function, with less damage to alveolar epithelium, resulting in reduced pulmonary injury.

Avaliação da completitude do Sistema de Informação de Agravos de Notificação da Tuberculose, Brasil, 2001-2006

Summary Objectives: to build indices for the evaluation of completeness in the Tuberculosis Notification Information System (Sinan-TB) and to apply them to large urban centers with high disease burden, between 2001 and 2006. Methodology: the general and for block indexes (identification; complementary; and follow-up) were created according to the per centage of non-completed data. Variables were classified as mandatory or essential. Results: a progressive worsening in the quality of the general index was observed between 2004 and 2006. When analyzing the indices of each block separately, it was noted that this result is largely due to the low level of the follow-up data completeness. Conclusion: the implementation of strategies to improve the quality of data entry for the Sinan-TB variables is recommended.

Pivotal Role of the 5-Lipoxygenase Pathway in Lung Injury after Experimental Sepsis

Postsepsis lung injury is a common clinical problem associated with significant morbidity and mortality. Leukotrienes (LTs) are important lipid mediators of infection and inflammation derived from the 5-lipoxygenase (5-LO) metabolism of arachidonate with the potential to contribute to lung damage after sepsis. To test the hypothesis that LTs are mediators of lung injury after sepsis, we assessed lung structure, inflammatory mediators, and mechanical changes after cecal ligation and puncture surgery in wild-type (WT) and 5-LO knockout (5-LO(-/-)) mice and in WT mice treated with a pharmacologic LT synthesis inhibitor (MK886) and LT receptor antagonists (CP105,696 and montelukast). Sixteen hours after surgery, WT animals exhibited severe lung injury (by histological analysis), substantial mechanical impairment (i.e., an increase in static lung elastance), an increase in neutrophil infiltration, and high levels of LTB4, cysteinyl-LTs (cys-LTs), prostaglandin E2, IL-1β, IL-6, IL-10, IL-17, KC (CXCL1), and monocyte chemotactic protein-1 (CCL2) in lung tissue and plasma. 5-LO(-/-) mice and WT mice treated with a pharmacologic 5-LO inhibitor were significantly protected from lung inflammation and injury. Selective antagonists for BLT1 or cys-LT1, the high-affinity receptors for LTB4 and cys-LTs, respectively, were insufficient to provide protection when used alone. These results point to an important role for 5-LO products in sepsis-induced lung injury and suggest that the use of 5-LO inhibitors may be of therapeutic benefit clinically.

Subnotificação da tuberculose no Sistema de Informação de Agravos de Notificação (SINAN): abandono primário de bacilíferos e captação de casos em outras fontes de informação usando linkage probabilístico

This study aimed to analyze underreporting of tuberculosis (TB) cases in the Information System on Notifiable Diseases (SINAN), based on the following data sources: Mortality Information System (SIM), Registry and Follow-up Book for TB Case Treatment (LPATB), and Laboratory Registry Book (LRLAB). Probabilistic record linkage was used between the SIM (2007-2008) and SINAN (2002-2008). A search was conducted in LPATB and LRLAB (2007-2008) for cases not recorded in SINAN. There were 125 deaths, of which 44.8% were not recorded in SINAN. In LPATB, 58 cases (5.1%) were in treatment and were not reported in SINAN. LRLAB showed 32 smear-positive cases not reported to SINAN and without treatment, representing primary default. Addition of the retrieved cases, led to a 14.6% increase in the incidence rate in 2007 and 11.6% in 2008. Underreporting of deaths from or with TB in the Mortality Information System and primary default revealed difficulties in access to adequate and timely treatment, calling for rethinking of strategies to detect cases for timely treatment.