Theranostic applications of phage display to control leishmaniasis: selection of biomarkers for serodiagnostics, vaccination, and immunotherapy

AbstractPhage display is a high-throughput subtractive proteomic technology used for the generation and screening of large peptide and antibody libraries. It is based on the selection of phage-fused surface-exposed peptides that recognize specific ligands and demonstrate desired functionality for diagnostic and therapeutic purposes. Phage display has provided unmatched tools for controlling viral, bacterial, fungal, and parasitic infections, and allowed identification of new therapeutic targets to treat cancer, metabolic diseases, and other chronic conditions. This review presents recent advancements in serodiagnostics and prevention of leishmaniasis -an important tropical parasitic disease- achieved using phage display for the identification of novel antigens with improved sensitivity and specificity. Our focus is on theranostics of visceral leishmaniasis with the aim to develop biomarker candidates exhibiting both diagnostic and therapeutic potential to fight this important, yet neglected, tropical disease.

Double pylorus: case report and review of the literature

Double pylorus is an unusual condition in which a double communication between the gastric antrum and the duodenal bulb occurs. It may be congenital, or it may be acquired complication of peptic ulcer disease. We present a case of double pylorus in a gentleman with epigastric pain and previous history of peptic ulcer disease. The relationship between Helicobacter pylori and this disease was assessed. A review of the literature, the role of associated diseases and the role of H. pylori are discussed.

Relationship between the morphologic alterations of vocal cords from adult autopsies and the cause of death

PURPOSE: The purpose of this study was to identify the possible alteration in the thickness of the epithelium basal membrane of the vocal cords and correlate it with the cause of death. METHOD: Larynxes collected from adult autopsies during the period of 1993 to 2001 were utilized. We used the hematoxylin-eosin and periodic acid-Schiff staining methods for the morphological and morphometric analysis. RESULTS: Sixty-six vocal cords were analysed; increased thickness was identified in 14 cases (21.2%), with equal proportions between the genders. Increased vocal-cord thickness was more frequent in patients of the white ethnicity (12 cases, 85.7%). Respiratory alterations were found in 10 (71.4%) of the cases with increased vocal-cord thickness. Of the patients that were maintained with mechanical ventilation before death, 7 (18.4%) had thickening of the basal membrane. Among the smokers, 9 (19.63%) had basal membrane thickening. CONCLUSION: No statistically significant differences were found between the cases in which the cause of death was related to respiratory diseases as compared to non-respiratory diseases and the thickening of the basal membrane of the vocal cords. However, new studies are needed in order to verify the etiopathogenesis of this thickening.

Dental and facial characteristics of patients with juvenile idiopathic arthritis

OBJECTIVE: It has been shown that the temporomandibular joint is frequently affected by juvenile idiopathic arthritis, and this degenerative disease, which may occur during facial growth, results in severe mandibular dysfunction. However, there are no studies that correlate oral health (tooth decay and gingival diseases) and temporomandibular joint dysfunction in patients with juvenile idiopathic arthritis. The aim of this study is to evaluate the oral and facial characteristics of the patients with juvenile idiopathic arthritis treated in a large teaching hospital. METHOD: Thirty-six patients with juvenile idiopathic arthritis (26 female and 10 male) underwent a systematic clinical evaluation of their dental, oral, and facial structures (DMFT index, plaque and gingival bleeding index, dental relationship, facial profile, and Helkimo's index). The control group was composed of 13 healthy children. RESULTS: The mean age of the patients with juvenile idiopathic arthritis was 10.8 years; convex facial profile was present in 12 juvenile idiopathic arthritis patients, and class II molar relation was present in 12 (P = .032). The indexes of plaque and gingival bleeding were significant in juvenile idiopathic arthritis patients with a higher number of superior limbs joints involved (P = .055). Anterior open bite (5) and temporomandibular joint noise (8) were present in the juvenile idiopathic arthritis group. Of the group in this sample, 94% (P = .017) had temporomandibular joint dysfunction, 80% had decreased mandibular opening (P = 0.0002), and mandibular mobility was severely impaired in 33% (P = .015). CONCLUSION: This study confirms that patients with juvenile idiopathic arthritis a) have a high incidence of mandibular dysfunction that can be attributed to the direct effect of the disease in the temporomandibular joint and b) have a higher incidence of gingival disease that can be considered a secondary effect of juvenile idiopathic arthritis on oral health.

MMP-9/RECK imbalance: a mechanism associated with high-grade cervical lesions and genital infection by Human Papillomavirus (HPV) and Chlamydia trachomatis

"Manuscript"

Nanotechnological approaches using curcumin and Withania somnifera: neuroprotection and antimicrobial activities

Tese de Doutoramento em Biologia de Plantas

Heart transplantation in neonates and children. Intermediate-term results

OBJECTIVE: To assess intermediate-term outcome in children who have undergone orthotopic heart transplantation. METHODS: We carried out a longitudinal and prospective study between October '92 and June '99 comprising 20 patients with ages ranging from 12 days to 7 years (mean of 2.8 years). We employed a double immunosuppression protocol with cyclosporine and azathioprine and induction therapy with polyclonal antithymocyte serum. Survival and complications resulting from the immunosuppression protocol were analyzed. RESULTS:The double immunosuppression protocol and the induction therapy with polyclonal antithymocyte serum resulted in an actuarial survival curve of 90% and 78.2% at 1 and 6 years, respectively, with a mean follow-up period of 3.6 years. One patient died due to acute rejection 40 days after transplantation; another patient died 2 years after transplantation due to lymphoproliferative disorder; a third patient died because of primary failure of the graft; and a fourth patient died due to bronchopneumonia. The major complications were as follows: acute rejection, infection, nephrotoxicity, and systemic hypertension. The means of rejection and infection episodes per patient were 2.9 and 3.4, respectively. After one year of transplantation, a slight reduction in the creatinine clearance and systemic hypertension were observed in 7 (38.9%) patients. CONCLUSION: Heart transplantation made life possible for those patients with complex congenital heart diseases and cardiomyopathies in refractory congestive heart failure constituting a therapeutical option for this group of patients in the terminal phase.

Epidemiological characteristics of congenital heart diseases in Londrina, Paraná South Brazil

OBJECTIVE: To determine the prevalence and other epidemiological characteristics of congenital heart diseases. METHODS: A retrospective population based study of children who were born in Londrina, from January '89 to December '98 (80,262 live births). Diagnoses were confirmed through autopsy, surgery, catheterization, or echocardiography. RESULTS: A total of 441 patients was as certained what corresponds to a prevalence of 5.494:1,000 live births. Ventricular septal defect was the commonest lesion. A small number of transpositions of the great vessels and of left ventricular hypoplasia was observed. A high propation of ventricular septal defect (28.3%) and atrioventricular septal defects (8.1%) occurred. Fifty-one (11.35%) affected children had syndromic diseases and 52 (12.01%) children had nonsyndromic anomalies. CONCLUSION: The prevalence of congenital heart diseases in Londrina is in accordance with that of other regions of the globe. This prevalence also may reflect the reality in the southern region of Brazil, because population characteristics are very similar in the 3 southernmost Brazilian states.

Pre-clinical trials for Machado-Joseph Disease: Hypothesis-based and hypothesis-free therapeutic approaches

Tese de Doutoramento em Ciências da Saúde

Mortality by Heart Failure and Ischemic Heart Disease in Brazil from 1996 to 2011

Background:Circulatory system diseases are the first cause of death in Brazil.Objective:To analyze the evolution of mortality caused by heart failure, by ischemic heart diseases and by ill-defined causes, as well as their possible relations, in Brazil and in the geoeconomic regions of the country (North, Northeast, Center-West, South and Southeast), from 1996 to 2011.Methods:Data were obtained from DATASUS and death declaration records with codes I20 and I24 for acute ischemic diseases, I25 for chronic ischemic diseases, and I50 for heart failure, and codes in chapter XIII for ill-defined causes, according to geoeconomic regions of Brazil, from 1996 to 2011.Results:Mortality rates due to heart failure declined in Brazil and its regions, except for the North and the Northeast. Mortality rates due to acute ischemic heart diseases increased in the North and Northeast regions, especially from 2005 on; they remained stable in the Center-West region; and decreased in the South and in the Southeast. Mortality due to chronic ischemic heart diseases decreased in Brazil and in the Center-West, South and Southeast regions, and had little variation in the North and in the Northeast. The highest mortality rates due to ill-defined causes occurred in the Northeast until 2005.Conclusions:Mortality due to heart failure is decreasing in Brazil and in all of its geoeconomic regions. The temporal evolution of mortality caused by ischemic heart diseases was similar to that of heart failure. The decreasing number of deaths due to ill-defined causes may represent the improvement in the quality of information about mortality in Brazil. The evolution of acute ischemic heart diseases ranged according to regions, being possibly confused with the differential evolution of ill-defined causes.

Infant Mortality in Novo Hamburgo: Associated Factors and Cardiovascular Causes

Background: Infant mortality has decreased in Brazil, but remains high as compared to that of other developing countries. In 2010, the Rio Grande do Sul state had the lowest infant mortality rate in Brazil. However, the municipality of Novo Hamburgo had the highest infant mortality rate in the Porto Alegre metropolitan region. Objective: To describe the causes of infant mortality in the municipality of Novo Hamburgo from 2007 to 2010, identifying which causes were related to heart diseases and if they were diagnosed in the prenatal period, and to assess the access to healthcare services. Methods: This study assessed infants of the municipality of Novo Hamburgo, who died, and whose data were collected from the infant death investigation records. Results: Of the 157 deaths in that period, 35.3% were reducible through diagnosis and early treatment, 25% were reducible through partnership with other sectors, 19.2% were non-preventable, 11.5% were reducible by means of appropriate pregnancy monitoring, 5.1% were reducible through appropriate delivery care, and 3.8% were ill defined. The major cause of death related to heart disease (13.4%), which was significantly associated with the variables ‘age at death’, ‘gestational age’ and ‘birth weight’. Regarding access to healthcare services, 60.9% of the pregnant women had a maximum of six prenatal visits. Conclusion: It is mandatory to enhance prenatal care and newborn care at hospitals and basic healthcare units to prevent infant mortality.

Prevalence of Risk for Obstructive Sleep Apnea Syndrome and Association With Risk Factors in Primary Care

Abstract Background: Obstructive sleep apnea syndrome (OSAS) is a chronic, progressive disease with high morbidity and mortality. It is underdiagnosed, especially among women. Objective: To study the prevalence of high risk for OSAS globally and for the Berlin Questionnaire (BQ) categories, and to evaluate the reliability of the BQ use in the population studied. Methods: Observational, cross-sectional study with individuals from the Niterói Family Doctor Program, randomly selected, aged between 45 and 99 years. The visits occurred between August/2011 and December/2012. Variables associated with each BQ category and with high risk for OSAS (global) were included in logistic regression models (p < 0.05). Results: Of the total (616), 403 individuals (65.4%) reported snoring. The prevalence of high risk for OSA was 42.4%, being 49.7% for category I, 10.2% for category II and 77.6% for category III. Conclusion: BQ showed an acceptable reliability after excluding the questions Has anyone noticed that you stop breathing during your sleep? and Have you ever dozed off or fallen asleep while driving?. This should be tested in further studies with samples mostly comprised of women and low educational level individuals. Given the burden of OSAS-related diseases and risks, studies should be conducted to validate new tools and to adapt BQ to better screen OSAS.

Accumulation of micronutrients by sweet sorghum under field conditions

Samples of two cultivars of sweet sorghum (Brandes and Rio) grown on a Dark Red Latosol (Latossolo Roxo, Barra Bonita, SP.) were collected at intervals of 20 days during their life cycle and the contents of micronutrients were determined by routine procedures. Usually the physiological stages in which the rate of absorption was higher were not the same for both varieties.

Exploration of the visual system : Part 2. In vivo analysis methods : virtual-reality optomotor system, fundus examination and fluorescent angiography

The mouse has emerged as an animal model for many diseases. At IRO, we have used this animal to understand the development of many eye diseases and treatment of some of them. Precise evaluation of vision is a prerequisite for both these approaches. In this unit we describe three ways to measure vision: testing the optokinetic response, and evaluating the fundus by direct observation and by fluorescent angiography.

Top Three Pharmacogenomics and Personalized Medicine Applications at the Nexus of Renal Pathophysiology and Cardiovascular Medicine.

Pharmacogenomics is a field with origins in the study of monogenic variations in drug metabolism in the 1950s. Perhaps because of these historical underpinnings, there has been an intensive investigation of 'hepatic pharmacogenes' such as CYP450s and liver drug metabolism using pharmacogenomics approaches over the past five decades. Surprisingly, kidney pathophysiology, attendant diseases and treatment outcomes have been vastly under-studied and under-theorized despite their central importance in maintenance of health, susceptibility to disease and rational personalized therapeutics. Indeed, chronic kidney disease (CKD) represents an increasing public health burden worldwide, both in developed and developing countries. Patients with CKD suffer from high cardiovascular morbidity and mortality, which is mainly attributable to cardiovascular events before reaching end-stage renal disease. In this paper, we focus our analyses on renal function before end-stage renal disease, as seen through the lens of pharmacogenomics and human genomic variation. We herein synthesize the recent evidence linking selected Very Important Pharmacogenes (VIP) to renal function, blood pressure and salt-sensitivity in humans, and ways in which these insights might inform rational personalized therapeutics. Notably, we highlight and present the rationale for three applications that we consider as important and actionable therapeutic and preventive focus areas in renal pharmacogenomics: 1) ACE inhibitors, as a confirmed application, 2) VDR agonists, as a promising application, and 3) moderate dietary salt intake, as a suggested novel application. Additionally, we emphasize the putative contributions of gene-environment interactions, discuss the implications of these findings to treat and prevent hypertension and CKD. Finally, we conclude with a strategic agenda and vision required to accelerate advances in this under-studied field of renal pharmacogenomics with vast significance for global public health.