Candida albicans PROTEIN PROFILE CHANGES IN RESPONSE TO THE BUTANOLIC EXTRACT OF Sapindus saponariaL.

Candida albicans is an opportunistic human pathogen that is capable of causing superficial and systemic infections in immunocompromised patients. Extracts of Sapindus saponaria have been used as antimicrobial agents against various organisms. In the present study, we used a combination of two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) to identify the changes in protein abundance of C. albicans after exposure to the minimal inhibitory concentration (MIC) and sub-minimal inhibitory concentration (sub-MIC) of the butanolic extract (BUTE) of S. saponaria and also to fluconazole. A total of six different proteins with greater than 1.5 fold induction or repression relative to the untreated control cells were identified among the three treatments. In general, proteins/enzymes involved with the glycolysis (GPM1, ENO1, FBA1), amino acid metabolism (ILV5, PDC11) and protein synthesis (ASC1) pathways were detected. In conclusion, our findings reveal antifungal-induced changes in protein abundance of C. albicans. By using the previously identified components of the BUTE of S. saponaria(e.g., saponins and sesquiterpene oligoglycosides), it will be possible to compare the behavior of compounds with unknown mechanisms of action, and this knowledge will help to focus the subsequent biochemical work aimed at defining the effects of these compounds.

AMERICAN CUTANEOUS LEISHMANIASIS WITH UNUSUAL CLINICAL PRESENTATION AND RESPONSE TO TREATMENT

The clinical manifestations and prognosis of cutaneous leishmaniasis (CL) can be influenced by the immune response of the patient and the species of the parasite. A case of atypical clinical presentation of CL, with development of non-characteristic lesions, poor response to therapy, and a long time to resolution is reported. Confirmatory laboratory tests included parasite detection, indirect immunofluorescence, Montenegro skin test, polymerase chain reaction, and parasite identification by multilocus enzyme electrophoresis. The parasite was identified as Leishmaniabraziliensis. The lesion was unresponsive to three complete courses of N-methylglucamine antimoniate intramuscular, and to treatment with pentamidine. The patient did not tolerate amphotericin B. The lesion finally receded after treatment with intravenous N-methylglucamine antimoniate. It is essential to ensure the accuracy of diagnosis and the appropriate treatment, which can include the use a second choice drug or a different route of administration.

Invasive Assessment of the Coronary Microcirculation Using the Index of Microcirculatory Resistance: Description and Validation of an Animal Model

INTRODUCTION: The index of microcirculatory resistance (IMR) enables/provides quantitative, invasive, and real-time assessment of coronary microcirculation status. AIMS: The primary aim of this study was to validate the assessment of IMR in a large animal model, and the secondary aim was to compare two doses of intracoronary papaverine, 5 and 10 mg, for induction of maximal hyperemia and its evolution over time. METHODS: Measurements of IMR were performed in eight pigs. Mean distal pressure (Pd) and mean transit time (Tmn) were measured at rest and at maximal hyperemia induced with intracoronary papaverine, 5 and 10 mg, and after 2, 5, 8 and 10 minutes. Disruption of the microcirculation was achieved by selective injection of 40-μm microspheres via a microcatheter in the left anterior descending artery. RESULTS: In each animal 14 IMR measurements were made. There were no differences between the two doses of papaverine regarding Pd response and IMR values - 11 ± 4.5 U with 5 mg and 10.6 ± 3 U with 10 mg (p=0.612). The evolution of IMR over time was also similar with the two doses, with significant differences from resting values disappearing after five minutes of intracoronary papaverine administration. IMR increased with disrupted microcirculation in all animals (41 ± 16 U, p=0.001). CONCLUSIONS: IMR provides invasive and real-time assessment of coronary microcirculation. Disruption of the microvascular bed is associated with a significant increase in IMR. A 5-mg dose of intracoronary papaverine is as effective as a 10-mg dose in inducing maximal hyperemia. After five minutes of papaverine administration there is no significant difference from resting hemodynamic status.

Time-of-flight secondary ion mass spectrometry: new application for urinary stones analysis

Dissertação para obtenção do Grau de Doutor em Engenharia Física

Empirical models for quantification of machining damage in composite materials

Dissertação para obtenção do Grau de Doutor em Engenharia Mecânica

Economic Evaluation of Ticagrelor for Secondary Prevention Following Acute Coronary Syndromes

INTRODUCTION AND OBJECTIVES: To estimate the cost-effectiveness and cost-utility of ticagrelor in the treatment of patients with acute coronary syndromes (unstable angina or myocardial infarction with or without ST-segment elevation), including patients treated medically and those undergoing percutaneous coronary intervention or coronary artery bypass grafting. METHODS: A short-term decision tree and a long-term Markov model were used to simulate the evolution of patients' life-cycles. Clinical effectiveness data were collected from the PLATO trial and resource use data were obtained from the Hospital de Santa Marta database, disease-related group legislation and the literature. RESULTS: Ticagrelor provides increases of 0.1276 life years and 0.1106 quality-adjusted life years (QALYs) per patient. From a societal perspective these clinical gains entail an increase in expenditure of €610. Thus the incremental cost per life year saved is €4780 and the incremental cost per QALY is €5517. CONCLUSIONS: The simulation results show that ticagrelor reduces events compared to clopidogrel. The costs of ticagrelor are partially offset by lower costs arising from events prevented. The use of ticagrelor in clinical practice is therefore cost-effective compared to generic clopidogrel.

Leg Ulcers in Antiphospholipid Syndrome Secondary to Systemic Lupus Erythematosus Treated with Intravenous Immunoglobulin

BACKGROUND: Despite encouraging reports on the efficacy of intravenous immunoglobulin (IVIg) in antiphospholipid syndrome, the clinical value of this treatment is not well established, and most of the data are based on case reports and small series of patients. OBSERVATION: We describe the significant improvement of leg ulcers with IVIg in a 61-year-old female, with diabetes mellitus, venous peripherical insufficiency and secondary antiphospholipid syndrome to systemic lupus erythematosus. CONCLUSIONS: This case illustrates a rare cause of leg ulcers and documents that IVIg may be an effective adjuvant treatment in the management of selected patients with antiphospholipid syndrome when conventional strategies using subcutaneous heparin and low-dose aspirin are insufficient.

Variation in Haemodynamic Monitoring for Major Surgery in European Nations: Secondary Analysis of the EuSOS Dataset

BACKGROUND: The use of cardiac output monitoring may improve patient outcomes after major surgery. However, little is known about the use of this technology across nations. METHODS: This is a secondary analysis of a previously published observational study. Patients aged 16 years and over undergoing major non-cardiac surgery in a 7-day period in April 2011 were included into this analysis. The objective is to describe prevalence and type of cardiac output monitoring used in major surgery in Europe. RESULTS: Included in the analysis were 12,170 patients from the surgical services of 426 hospitals in 28 European nations. One thousand four hundred and sixteen patients (11.6 %) were exposed to cardiac output monitoring, and 2343 patients (19.3 %) received a central venous catheter. Patients with higher American Society of Anesthesiologists (ASA) scores were more frequently exposed to cardiac output monitoring (ASA I and II, 643 patients [8.6 %]; ASA III-V, 768 patients [16.2 %]; p < 0.01) and central venous catheter (ASA I and II, 874 patients [11.8 %]; ASA III-V, 1463 patients [30.9 %]; p < 0.01). In elective surgery, 990 patients (10.8 %) were exposed to cardiac output monitoring, in urgent surgery 252 patients (11.7 %) and in emergency surgery 173 patients (19.8 %). A central venous catheter was used in 1514 patients (16.6 %) undergoing elective, in 480 patients (22.2 %) undergoing urgent and in 349 patients (39.9 %) undergoing emergency surgery. Nine hundred sixty patients (7.9 %) were monitored using arterial waveform analysis, 238 patients (2.0 %) using oesophageal Doppler ultrasound, 55 patients (0.5 %) using a pulmonary artery catheter and 44 patients (2.0 %) using other technologies. Across nations, cardiac output monitoring use varied from 0.0 % (0/249 patients) to 27.5 % (19/69 patients), whilst central venous catheter use varied from 5.6 % (7/125 patients) to 43.2 % (16/37 patients). CONCLUSIONS: One in ten patients undergoing major surgery is exposed to cardiac output monitoring whilst one in five receives a central venous catheter. The use of both technologies varies widely across Europe.

The liver in secondary syphilis clinical, laboratory and histopathological investigation of 22 patients without jaundice

22 patients with a history of syphilitic contact, skin lesions and positive serology were evaluated by physical examination, tiver function tests and líver biopsy for evidence of hepatic lesions secondary to treponema infection. Only minimal evidences of hepatic damage were revealed by clinical examination and liver function tests. On biopsy 21 cases of NSRH were noted with one case of gramioma formation. No spirochaetes were found, so these findings could not be attributed to a direct action of the treponema.

Autism Spectrum Disorder Secondary to Enterovirus Encephalitis

Millions of children are infected by enteroviruses each year, usually exhibiting only mild symptoms. Nevertheless, these viruses are also associated with severe and life-threatening infections, such as meningitis and encephalitis. We describe a 32-month-old patient with enteroviral encephalitis confirmed by polymerase chain reaction in cerebrospinal fluid, with unfavorable clinical course with marked developmental regression, autistic features, persistent stereotypes and aphasia. She experienced slow clinical improvement, with mild residual neurologic and developmental deficits at follow-up. Viral central nervous system infections in early childhood have been associated with autism spectrum disorders but the underlying mechanisms are still poorly understood. This case report is significant in presenting a case of developmental regression with autistic features and loss of language improving on follow-up. To our knowledge, this is the first published report of enterovirus encephalitis leading to an autism spectrum disorder.

Mortality of Dipetalogaster maximus (uhler) in response to temperature and humidity

Observations were made on the mortality of Dipetalogaster maximus in relation to humidity and temperature in controlled conditions. The bugs survived longer at higher relative humidities and at lower temperatures, but when these results were plotted against vapour pressure déficit, no independent temperature effect was seen. The results may be explained by thefaster depletion of water reserves at higher vapour pressure deficits. D. maximus did not increase its resistance to water vapour transferat higher vapour pressure deficits. In orderto increase survival rates when D. maximus is used for xenodiagnosis in field conditions it should be protected against high temperatures and low humidities.

Increased osmotic sensitivity for antidiuretic response in chronic chagas' disease

The osmotic threshold for attaining the antidiuretic response to hypertonic saline infusion and Progressive dehydration was studied in 31 patients with the chronic form of Chagas' disease and 16 control patients. The chagasic patients exhibited enhanced osmoticsensitivity to the antidiuretic response. This was demonstrated by lower values of the increments in plasma osmolarity sufficient to induce a significant fall in water clearance, without alterations in the osmolar clearance or creatinine excretion. The time needed to attain the antidiuretic response was shorterfor chagasics in relation to normal subjects. The results suggest the existence of a disturbance in the fine control of osmoregulation in the chagasic patients. They are interpreted to be a consequence of the denervation in hypothalamic or extrahypothalamic areas that regulate the secretion of vasopressin in chronic Chagas' disease.

Investigation of the response to the enterobacterial common antigen after typhoid vaccination

Antibodies against the Salmonella typhi enterobacterial common antigen (ECA) and the O and H antigens were investigated in sera from healthy male subjects who had been previously vaccinated with the typhoid vaccine. No serological response to ECA was observed. Sera from subjects not previously vaccinated presented titers of ECA hemagglutinins which quantitatively were related to the presence ofH titers, but not to O agglutinins but with no statistical significance. The results are discussed in relation to the possible protective immunological mechanisms in typhoid fever.