Human Tissue Kallikrein Activity in Angiographically Documented Chronic Stable Coronary Artery Disease

AbstractBackground:Human tissue kallikrein (hK1) is a key enzyme in the kallikrein–kinin system (KKS). hK1-specific amidase activity is reduced in urine samples from hypertensive and heart failure (HF) patients. The pathophysiologic role of hK1 in coronary artery disease (CAD) remains unclear.Objective:To evaluate hK1-specific amidase activity in the urine of CAD patientsMethods:Sixty-five individuals (18–75 years) who underwent cardiac catheterism (CATH) were included. Random midstream urine samples were collected immediately before CATH. Patients were classified in two groups according to the presence of coronary lesions: CAD (43 patients) and non-CAD (22 patients). hK1 amidase activity was estimated using the chromogenic substrate D-Val-Leu-Arg-Nan. Creatinine was determined using Jaffé’s method. Urinary hK1-specific amidase activity was expressed as µM/(min · mg creatinine) to correct for differences in urine flow rates.Results:Urinary hK1-specific amidase activity levels were similar between CAD [0.146 µM/(min ·mg creatinine)] and non-CAD [0.189 µM/(min . mg creatinine)] patients (p = 0.803) and remained similar to values previously reported for hypertensive patients [0.210 µM/(min . mg creatinine)] and HF patients [0.104 µM/(min . mg creatinine)]. CAD severity and hypertension were not observed to significantly affect urinary hK1-specific amidase activity.Conclusion:CAD patients had low levels of urinary hK1-specific amidase activity, suggesting that renal KKS activity may be reduced in patients with this disease.

Efficacy of Patient Selection for Diagnostic Coronary Angiography in Suspected Coronary Artery Disease

AbstractBackground:Guidelines recommend that in suspected stable coronary artery disease (CAD), a clinical (non-invasive) evaluation should be performed before coronary angiography.Objective:We assessed the efficacy of patient selection for coronary angiography in suspected stable CAD.Methods:We prospectively selected consecutive patients without known CAD, referred to a high-volume tertiary center. Demographic characteristics, risk factors, symptoms and non-invasive test results were correlated to the presence of obstructive CAD. We estimated the CAD probability based on available clinical data and the incremental diagnostic value of previous non-invasive tests.Results:A total of 830 patients were included; median age was 61 years, 49.3% were males, 81% had hypertension and 35.5% were diabetics. Non-invasive tests were performed in 64.8% of the patients. At coronary angiography, 23.8% of the patients had obstructive CAD. The independent predictors for obstructive CAD were: male gender (odds ratio [OR], 3.95; confidence interval [CI] 95%, 2.70 - 5.77), age (OR for 5 years increment, 1.15; CI 95%, 1.06 - 1.26), diabetes (OR, 2.01; CI 95%, 1.40 - 2.90), dyslipidemia (OR, 2.02; CI 95%, 1.32 - 3.07), typical angina (OR, 2.92; CI 95%, 1.77 - 4.83) and previous non-invasive test (OR 1.54; CI 95% 1.05 - 2.27).Conclusions:In this study, less than a quarter of the patients referred for coronary angiography with suspected CAD had the diagnosis confirmed. A better clinical and non-invasive assessment is necessary, to improve the efficacy of patient selection for coronary angiography.

Variations in the Prevalence of Risk Factors for Coronary Artery Disease in Rio Grande do Sul-Brazil: A Comparative Analysis between 2002 and 2014

Abstract Background: Due to the importance of coronary artery disease (CAD), continuous investigation of the risk factors (RFs) is needed. Objective: To evaluate the prevalence of RFs for CAD in cities in Rio Grande do Sul State, and compare it with that reported in a similar study conducted in the same cities in 2002. Methods: Cross-sectional study on 1,056 healthy adults, investigating the prevalence and absolute and relative frequencies of the following RFs for CAD: obesity, systemic arterial hypertension (SAH), dyslipidemias, smoking, sedentary lifestyle, diabetes mellitus, and family history, as well as age and sex. Data was collected in 19 cities, host of the Offices of the Regional Coordinators of Health, as in the 2002 study. Results: Twenty-six percent of the sample consisted of older adults and 57% were women. The prevalence of sedentary lifestyle was 44%, history family 50%, smoking 23%, overweight/obesity 68%, dyslipidemia (high cholesterol levels) 43%, SAH 40%, and diabetes 11%. When compared to the 2002 study, the prevalence of active smoking and sedentary behavior decreased, whereas the prevalence of hypertension, dyslipidemia and obesity increased. Obesity is the most prevalent RF in women, and SAH the most prevalent in men. Conclusions: The prevalence of RFs for CAD in Rio Grande do Sul State remains high. Hypertension, obesity and dyslipidemia are still prevalent and require major prevention programs. Smoking and physical inactivity have decreased in the state, suggesting the efficacy of related campaigns.

Acquired resistance of mice against S. mansoni and lung granulomatous reaction induced by BCG

Studies carried out in Sw outbred mice showed that there is no correlation between the degree of lung granulomatous reaction and the level of acquired resistance against S. mansoni infection induced by BCG.

Aneurysms of saphenous vein grafts as late complication of coronary artery bypass surgery: successful exclusion by percutaneous transcatheter embolization.

We report a case of a 71-year-old man with a long coronary artery disease history and two sets of coronary artery bypass grafts. He developed large aortocoronary saphenous vein graft aneurysms in the two grafts from the first set of aortocoronary saphenous venous 20 years later. During the previous 3 years, the aneurysms grew in diameter from 22 to 50 mm. Because of severe renal insufficiency, and in order to avoid jeopardizing the late normal coronary artery bypass grafts by further thoracic surgery, we excluded successfully these altered grafts percutaneously by using 13 coils during the same procedure.

Albuterol delivery in an in vitro pediatric ventilator lung model: comparison of jet, ultrasonic, and mesh nebulizers.

OBJECTIVE: : To determine the influence of nebulizer types and nebulization modes on bronchodilator delivery in a mechanically ventilated pediatric lung model. DESIGN: : In vitro, laboratory study. SETTING: : Research laboratory of a university hospital. INTERVENTIONS: : Using albuterol as a marker, three nebulizer types (jet nebulizer, ultrasonic nebulizer, and vibrating-mesh nebulizer) were tested in three nebulization modes in a nonhumidified bench model mimicking the ventilatory pattern of a 10-kg infant. The amounts of albuterol deposited on the inspiratory filters (inhaled drug) at the end of the endotracheal tube, on the expiratory filters, and remaining in the nebulizers or in the ventilator circuit were determined. Particle size distribution of the nebulizers was also measured. MEASUREMENTS AND MAIN RESULTS: : The inhaled drug was 2.8% ± 0.5% for the jet nebulizer, 10.5% ± 2.3% for the ultrasonic nebulizer, and 5.4% ± 2.7% for the vibrating-mesh nebulizer in intermittent nebulization during the inspiratory phase (p < 0.01). The most efficient nebulizer was the vibrating-mesh nebulizer in continuous nebulization (13.3% ± 4.6%, p < 0.01). Depending on the nebulizers, a variable but important part of albuterol was observed as remaining in the nebulizers (jet and ultrasonic nebulizers), or being expired or lost in the ventilator circuit (all nebulizers). Only small particles (range 2.39-2.70 µm) reached the end of the endotracheal tube. CONCLUSIONS: : Important differences between nebulizer types and nebulization modes were seen for albuterol deposition at the end of the endotracheal tube in an in vitro pediatric ventilator-lung model. New aerosol devices, such as ultrasonic and vibrating-mesh nebulizers, were more efficient than the jet nebulizer.

Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008.

OBJECTIVE: To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock," published in 2004. DESIGN: Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. METHODS: We used the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation (1) indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost) or clearly do not. Weak recommendations (2) indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. RESULTS: Key recommendations, listed by category, include early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures before antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7-10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure > or = 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for postoperative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7-9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B), targeting a blood glucose < 150 mg/dL after initial stabilization (2C); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper gastrointestinal bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); and a recommendation against the use of recombinant activated protein C in children (1B). CONCLUSIONS: There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients.

Uric acid is a danger signal activating NALP3 inflammasome in lung injury inflammation and fibrosis.

RATIONALE: Lung injury leads to pulmonary inflammation and fibrosis through myeloid differentiation primary response gene 88 (MyD88) and the IL-1 receptor 1 (IL-1R1) signaling pathway. The molecular mechanisms by which lung injury triggers IL-1beta production, inflammation, and fibrosis remain poorly understood. OBJECTIVES: To determine if lung injury depends on the NALP3 inflammasome and if bleomycin (BLM)-induced lung injury triggers local production of uric acid, thereby activating the NALP3 inflammasome in the lung. Methods: Inflammation upon BLM administration was evaluated in vivo in inflammasome-deficient mice. Pulmonary uric acid accumulation, inflammation, and fibrosis were analyzed in mice treated with the inhibitor of uric acid synthesis or with uricase, which degrades uric acid. MEASUREMENTS AND MAIN RESULTS: Lung injury depends on the NALP3 inflammasome, which is triggered by uric acid locally produced in the lung upon BLM-induced DNA damage and degradation. Reduction of uric acid levels using the inhibitor of uric acid synthesis allopurinol or uricase leads to a decrease in BLM-induced IL-1beta production, lung inflammation, repair, and fibrosis. Local administration of exogenous uric acid crystals recapitulates lung inflammation and repair, which depend on the NALP3 inflammasome, MyD88, and IL-1R1 pathways and Toll-like receptor (TLR)2 and TLR4 for optimal inflammation but are independent of the IL-18 receptor. CONCLUSIONS: Uric acid released from injured cells constitutes a major endogenous danger signal that activates the NALP3 inflammasome, leading to IL-1beta production. Reducing uric acid tissue levels represents a novel therapeutic approach to control IL-1beta production and chronic inflammatory lung pathology.

Filariopsis barretoi (travassos, 1921) (Nematoda: metastrongyloidea) lung parasite of primates from South America - taxonomy, synonyms and pathology

Nematodes and fragments of lungs from Cebus ssp., Callithrix jacchus (l.) and Saimiri sciureus (L.) were studied. The worms from Cebus and Callithrix must be called Filariopsis barretoi (Travassos, 1921). The names Filariopsis arator Chandler, 1931 and Filaroides cebi Gebauer, 1933 are synonymized to F. barretoi. The status of Filariopsis gordius (Travassos, 1921) remains uncertain. The pathology is described. The parasites are located in the pulmonary paranchyma, near the pleural surface, constituting nodules.