Insight into the multicopper oxidases stability

Dissertation presented to obtain the PhD degree in Biochemistry

Calciphylaxis: a Literature Review Based in Two Case Reports

Calciphylaxis is a rare and devastating obliterative vasculopathy, leading to ischemia and subcutaneous necrosis. In most cases it affects patients with renal disease and is associated with high morbidity and mortality. We present two case reports followed recently in our department, and a literature review on this topic. Case one refers to an 80 -year -old Caucasian woman with chronic kidney disease stage 5 and primary hyperparathyroidism with secondary brown tumour and calciphylaxis. Case two refers to a 59 -year -old Caucasian woman admitted with severe nephrotic syndrome associated with amyloidosis, that developed a catastrophic picture of calciphylaxis, ending in the patient’s death. There is a critical need to understand the pathogenesis of calciphylaxis. Its comprehension is the only way to improve the survival of these patients, and may help to elucidate the pathophysiology of vascular calcification in general. Educating physicians in the prevention and early detection of calciphylaxis is crucial. Only by increasing the knowledge about risk factors, pathophysiology, response to treatment and outcome, will we be able to improve prophylaxis and therapy of patients with calciphylaxis, decreasing the high mortality of this entity.

DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV NEGATIVE BRAZILIAN PATIENTS

Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic in Brazil. Disseminated clinical forms are uncommon in immunocompetent individuals. We describe two HIV-negative patients with disseminated fungal infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies of suprarenal lesions. Both were treated for a prolonged period with oral antifungal agents, and both showed favorable outcomes.

Epidemiological studies of Streptococcus pneumoniae carriage in the post-vaccination era among two risk groups: children and the elderly

Dissertation presented to obtain the Ph.D. degree in Biology/ Molecular Biology

Personality, Brain Asymmetry, and Neuroendocrine Reactivity in Two Immune-Mediated Disorders: a Preliminary Report

Development of some immune-mediated disorders may depend on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. To explore neuropsychologic mechanisms in relation to the abnormal endocrine reactivity in patients with systemic lupus erythematosus (SLE) and chronic hepatitis C (CHC) we used the corticotropin releasing hormone (CRH) test, the Minnesota Multiphasic Personality Inventory (MMPI), and the Edinburgh Inventory of Manual Preference Inventory (EIMP). Compared to controls, the adrenocorticotrophic hormone (ACTH) response to CRH was reduced in CHC, while SLE presented reduced baseline dehydroepiandrosterone sulfate levels; higher neurotic scores were found in SLE and higher behavior deviant scores in CHC. Peak ACTH levels were a significant factor for the MMPI profile variability, while the manual preference score was a significant factor for the ACTH response. Personality and manual preference contribute to neuroendocrine abnormalities. Different behavioral and neuroimmunoendocrine models emerge for these disorders.

INTESTINAL AND PULMONARY INFECTION BY Cryptosporidium parvum IN TWO PATIENTS WITH HIV/AIDS

We describe two patients with HIV/AIDS who presented pulmonary and intestinal infection caused by Cryptosporidium parvum, with a fatal outcome. The lack of available description of changes in clinical signs and radiographic characteristics of this disease when it is located in the extra-intestinal region causes low prevalence of early diagnosis and a subsequent lack of treatment.

SURVIVAL CAPACITY OF Arcobacter butzleri INOCULATED IN POULTRY MEAT AT TWO DIFFERENT REFRIGERATION TEMPERATURES

Arcobacter spp. are emerging enteropathogens and potential zoonotic agents that can be transmitted by food and water, being considered a public health risk. The high isolation rate of these bacteria from poultry products suggests that it may be a major source of human infections. One hallmark for differentiating the genus Arcobacter fromCampylobacter includes their growing capacity at low temperatures (15-30 °C) under aerobic conditions. However, little is known about the population density variation of these bacteria at different refrigeration temperatures. The aim of this study was to determine the survival behavior of two different Arcobacter butzleri concentrations (104 CFU/mL and 107 CFU/mL) inoculated on chicken legs and held at two different refrigeration temperatures (4 and 10 °C) throughout storage time. Results have shown that A. butzleri had growing capacity both at 4 and 10 °C. No statistical difference between the survival trends was found for both bacterial concentrations and temperatures tested. This study shows that A. butzleri is a robust species with regard to storage temperature, and represents a potential health risk for poultry meat consumers.

Electron transfer complex between nitrous oxide reductase and cytochrome c552 from Pseudomonas nautica: kinetic, nuclear magnetic resonance, and docking studies

Biochemistry. 2008 Oct 14;47(41):10852-62. doi: 10.1021/bi801375q

The isolation and characterization of cytochrome c nitrite reductase subunits (NrfA and NrfH) from Desulfovibrio desulfuricans ATCC 27774

Eur. J. Biochem. 270, 3904–3915 (2003) doi:10.1046/j.1432-1033.2003.03772.x

Two Novel CMY-2-Type β-Lactamases Encountered in Clinical Escherichia Coli Isolates

BACKGROUND: Chromosomally encoded AmpC β-lactamases may be acquired by transmissible plasmids which consequently can disseminate into bacteria lacking or poorly expressing a chromosomal bla AmpC gene. Nowadays, these plasmid-mediated AmpC β-lactamases are found in different bacterial species, namely Enterobacteriaceae, which typically do not express these types of β-lactamase such as Klebsiella spp. or Escherichia coli. This study was performed to characterize two E. coli isolates collected in two different Portuguese hospitals, both carrying a novel CMY-2-type β-lactamase-encoding gene. FINDINGS: Both isolates, INSRA1169 and INSRA3413, and their respective transformants, were non-susceptible to amoxicillin, amoxicillin plus clavulanic acid, cephalothin, cefoxitin, ceftazidime and cefotaxime, but susceptible to cefepime and imipenem, and presented evidence of synergy between cloxacilin and cefoxitin and/or ceftazidime. The genetic characterization of both isolates revealed the presence of bla CMY-46 and bla CMY-50 genes, respectively, and the following three resistance-encoding regions: a Citrobacter freundii chromosome-type structure encompassing a blc-sugE-bla CMY-2-type -ampR platform; a sul1-type class 1 integron with two antibiotic resistance gene cassettes (dfrA1 and aadA1); and a truncated mercury resistance operon. CONCLUSIONS: This study describes two new bla CMY-2-type genes in E. coli isolates, located within a C. freundii-derived fragment, which may suggest their mobilization through mobile genetic elements. The presence of the three different resistance regions in these isolates, with diverse genetic determinants of resistance and mobile elements, may further contribute to the emergence and spread of these genes, both at a chromosomal or/and plasmid level.

The vaccination of h uman beings with live avirulent vaccine of Trypanosoma cruzi: A two year follow-up of the first two cases

A two year follow-up of the first two volunteers vaccinated icith the live PF Trypanosoma cruzi strain demonstrated that the parasitological and clinical test were negative during and after that period. Of the serological tests employed, the CFT presented, in only one case, conflicting results, particulary in one laboratory and among different laboratories. However negative results were greater than all doubtful and positive one combined. The IFT icere negative in both patients. Some comments are made about the sensibility and specificity of these tests. The author concluded that the vaccine, in spite of the very large dose used in these cases, seems to be safe for human beings.

Effects of Local Anesthetic on the Time Between Analgesic Boluses and the Duration of Labor in Patient-Controlled Epidural Analgesia: Prospective Study of Two Ultra-Low Dose Regimens of Ropivacaine and Sufentanil

BACKGROUND: Patient-controlled epidural analgesia with low concentrations of anesthetics is effective in reducing labor pain. The aim of this study was to assess and compare two ultra-low dose regimens of ropivacaine and sufentanil (0.1% ropivacaine plus 0.5 μg.ml-1 sufentanil vs. 0.06% ropivacaine plus 0.5 μg.ml-1 sufentanil) on the intervals between boluses and the duration of labor. MATERIAL AND METHODS: In this non-randomized prospective study, conducted between January and July 2010, two groups of parturients received patient-controlled epidural analgesia: Group I (n = 58; 1 mg.ml-1 ropivacaine + 0.5 μg.ml-1 sufentanil) and Group II (n = 57; 0.6 mg.ml-1 ropivacaine + 0.5 μg.ml-1 sufentanil). Rescue doses of ropivacaine at the concentration of the assigned group without sufentanil were administered as necessary. Pain, local anesthetic requirements, neuraxial blockade characteristics, labor and neonatal outcomes, and maternal satisfaction were recorded. RESULTS: The ropivacaine dose was greater in Group I (9.5 [7.7-12.7] mg.h-1 vs. 6.1 [5.1-9.8 mg.h-1], p < 0.001). A time increase between each bolus was observed in Group I (beta = 32.61 min, 95% CI [25.39; 39.82], p < 0.001), whereas a time decrease was observed in Group II (beta = -1.40 min, 95% CI [-2.44; -0.36], p = 0.009). The duration of the second stage of labor in Group I was significantly longer than that in Group II (78 min vs. 65 min, p < 0.001). CONCLUSIONS: Parturients receiving 0.06% ropivacaine exhibited less evidence of cumulative effects and exhibited faster second stage progression than those who received 0.1% ropivacaine.

Endoscopic Treatment of Early Gastric Obstruction After Sleeve Gastrectomy: Report of Two Cases

Morbid obesity is an epidemic and complex disease which imposes a multidisciplinary approach. Laparoscopic sleeve gastrectomy has become a frequent procedure given its effi- cacy and safety compared to other surgical options. However, it isn’t free from complications. Lax gastric fixation or incorrect positioning of the stomach during surgery can result in early gastric outlet obstruction caused by a volvulus-like mechanism by rotation of the stomach around its anatomic axes. This report refers to two cases of post sleeve gastric torsion resulting in persisting vomiting after initiating oral intake. The diagnosis was confirmed by upper gastrointestinal-contrast study and gastroscopy. In both cases, a fully covered self-expandable metallic stentwas insertedwhich prompted the gastric lumen to become permeable resulting in symptomatic resolution. The stents were removed endoscopically aftertwo and three months. Beyond more than three years offollow-up,the patients remain asymptomatic and no recurring ‘‘stenosis’’ was noticed.In these cases the use offully covered self-expandable metallic stents demonstrated to be effective and safe in the treatment of post sleeve gastric torsion.

Validation of Two US Risk Scores for Percutaneous Coronary Intervention in a Single-Center Portuguese Population of Patients with Acute Coronary Syndrome

INTRODUCTION: New scores have been developed and validated in the US for in-hospital mortality risk stratification in patients undergoing coronary angioplasty: the National Cardiovascular Data Registry (NCDR) risk score and the Mayo Clinic Risk Score (MCRS). We sought to validate these scores in a European population with acute coronary syndrome (ACS) and to compare their predictive accuracy with that of the GRACE risk score. METHODS: In a single-center ACS registry of patients undergoing coronary angioplasty, we used the area under the receiver operating characteristic curve (AUC), a graphical representation of observed vs. expected mortality, and net reclassification improvement (NRI)/integrated discrimination improvement (IDI) analysis to compare the scores. RESULTS: A total of 2148 consecutive patients were included, mean age 63 years (SD 13), 74% male and 71% with ST-segment elevation ACS. In-hospital mortality was 4.5%. The GRACE score showed the best AUC (0.94, 95% CI 0.91-0.96) compared with NCDR (0.87, 95% CI 0.83-0.91, p=0.0003) and MCRS (0.85, 95% CI 0.81-0.90, p=0.0003). In model calibration analysis, GRACE showed the best predictive power. With GRACE, patients were more often correctly classified than with MCRS (NRI 78.7, 95% CI 59.6-97.7; IDI 0.136, 95% CI 0.073-0.199) or NCDR (NRI 79.2, 95% CI 60.2-98.2; IDI 0.148, 95% CI 0.087-0.209). CONCLUSION: The NCDR and Mayo Clinic risk scores are useful for risk stratification of in-hospital mortality in a European population of patients with ACS undergoing coronary angioplasty. However, the GRACE score is still to be preferred.