Carbon materials as new generation of new electron shuttles for the anaerobic degradation of environmental xenobiotics

Tese de Doutoramento em Engenharia Química e Biológica

Clinical diagnosis of 80 cases of dementia in a university hospital

OBJECTIVE: This study aims to estimate the prevalence of dementia subtypes and to assess the socio-demographic data of patients attending the outpatient clinic of dementia at Hospital das Clínicas from January 2008 to December 2009, in the city of Goiânia-GO, Brazil. METHODS: Procedures provided for diagnosis included physical and neurological examination, laboratory tests, neuroimaging and DSM-IV. The functional capacity and level of cognitive deficit were assessed by Pfeffer Functional Activities Questionnaire (Pfeffer-FAQ) and Mini-Mental State Examination (MMSE), respectively. RESULTS: Eighty patients met the criteria for dementia. The mean age was 63.48 (± 16.85) years old, the schooling was 3.30 (± 3.59) years old, the MMSE was 13.89 (± 7.79) and Pfeffer 17.73 (± 9.76). The Vascular Dementia (VD; 17.5%) was the most frequent cause of dementia, followed by Lewy body dementia (LBD) and Alzheimer's disease (AD) (12.25%). CONCLUSION: Considering entire sample and only the elderly over 60 years, VD, AD and LBD are the most common subtypes observed at both groups. Further epidemiological studies are necessary to confirm such rates, which may have a considerable impact on the organization and planning of healthcare services in our country.

Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication

Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of three genes-SMYD2, SETD3, and NO66-was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity (AUC=0.959), and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC: 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness.

Presence of dual diagnosis between users and non-users of licit and illicit drugs in Brazil

ABSTRACT Objective Investigate the occurrence of dual diagnosis in users of legal and illegal drugs. Methods It is an analytical, cross-sectional study with a quantitative approach, non-probabilistic intentional sampling, carried out in two centers for drug addiction treatment, by means of individual interviews. A sociodemographic questionnaire, the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) and the Mini-International Neuropsychiatric Interview (MINI) were used. Results One hundred and ten volunteers divided into abstinent users (group 1), alcoholics (group 2) and users of alcohol and illicit drugs (group 3). The substances were alcohol, tobacco, crack and marijuana. A higher presence of dual diagnosis in group 3 (71.8%) was observed, which decreased in group 2 (60%) and 37.1% of drug abstinent users had psychiatric disorder. Dual diagnosis was associated with the risk of suicide, suicide attempts and the practice of infractions. The crack consumption was associated with the occurrence of major depressive episode and antisocial personality disorder. Conclusion It was concluded that the illicit drug users had a higher presence of dual diagnosis showing the severity of this clinical condition. It is considered essential that this clinical reality is included in intervention strategies in order to decrease the negative effects of consumption of these substances and provide better quality of life for these people.

Female hippocampus vulnerability to environmental stress, a precipitating factor in tau aggregation pathology

Tau-mediated neurodegeneration is a central event in Alzheimer's disease (AD) and other tauopathies. Consistent with suggestions that lifetime stress may be a clinically-relevant precipitant of AD pathology, we previously showed that stress triggers tau hyperphosphorylation and accumulation; however, little is known about the etiopathogenic interaction of chronic stress with other AD risk factors, such as sex and aging. This study focused on how these various factors converge on the cellular mechanisms underlying tau aggregation in the hippocampus of chronically stressed male and female (middle-aged and old) mice expressing the most commonly found disease-associated Tau mutation in humans, P301L-Tau. We report that environmental stress triggers memory impairments in female, but not male, P301L-Tau transgenic mice. Furthermore, stress elevates levels of caspase-3-truncated tau and insoluble tau aggregates exclusively in the female hippocampus while it also alters the expression of the molecular chaperones Hsp90, Hsp70, and Hsp105, thus favoring accumulation of tau aggregates. Our findings provide new insights into the molecular mechanisms through which clinically-relevant precipitating factors contribute to the pathophysiology of AD. Our data point to the exquisite sensitivity of the female hippocampus to stress-triggered tau pathology.

Lipids under stress - a lipidomic approach for the study of mood disorders

The emerging field of lipidomics has identified lipids as key players in disease physiology. Their physicochemical diversity allows precise control of cell structure and signaling events through modulation of membrane prop- erties and trafficking of proteins. As such, lipids are important regulators of brain function and have been implicated in neurodegenerative and mood disorders. Importantly, environmental chronic stress has been associated with anxiety and depression and its exposure in rodents has been extensively used as a model to study these diseases. With the accessibility to modern mass- spectrometry lipidomic platforms, it is now possible to snapshot the extensively interconnected lipid network. Here, we review the fundamentals of lipid biology and outline a framework for the interpretation of lipidomic studies as a new approach to study brain pathophysiology. Thus, lipid profiling provides an exciting avenue for the identification of disease signatures with important implications for diagnosis and treatment of mood disorders.

Fatal pulmonary embolism in hospitalized patients. Clinical diagnosis versus pathological confirmation

OBJECTIVE - To assess the incidence of fatal pulmonary embolism (FPE), the accuracy of clinical diagnosis, and the profile of patients who suffered an FPE in a tertiary University Hospital. METHODS - Analysis of the records of 3,890 autopsies performed at the Department of General Pathology from January 1980 to December 1990. RESULTS - Among the 3,980 autopsies, 109 were cases of clinically suspected FPE; of these, 28 cases of FPE were confirmed. FPE accounted for 114 deaths, with clinical suspicion in 28 cases. The incidence of FPE was 2.86%. No difference in sex distribution was noted. Patients in the 6th decade of life were most affected. The following conditions were more commonly related to FPE: neoplasias (20%) and heart failure (18.5%). The conditions most commonly misdiagnosed as FPE were pulmonary edema (16%), pneumonia (15%) and myocardial infarction (10%). The clinical diagnosis of FPE showed a sensitivity of 25.6%, a specificity of 97.9%, and an accuracy of 95.6%. CONCLUSION - The diagnosis of pulmonary embolism made on clinical grounds still has considerable limitations.

Aromatic amines sources, environmental impact and remediation

Aromatic amines are widely used industrial chemicals as their major sources in the environment include several chemical industry sectors such as oil refining, synthetic polymers, dyes, adhesives, rubbers, perfume, pharmaceuticals, pesticides and explosives. They result also from diesel exhaust, combustion of wood chips and rubber and tobacco smoke. Some types of aromatic amines are generated during cooking, special grilled meat and fish, as well. The intensive use and production of these compounds explains its occurrence in the environment such as in air, water and soil, thereby creating a potential for human exposure. Since aromatic amines are potential carcinogenic and toxic agents, they constitute an important class of environmental pollutants of enormous concern, which efficient removal is a crucial task for researchers, so several methods have been investigated and applied. In this chapter the types and general properties of aromatic amine compounds are reviewed. As aromatic amines are continuously entering the environment from various sources and have been designated as high priority pollutants, their presence in the environment must be monitored at concentration levels lower than 30 mg L1, compatible with the limits allowed by the regulations. Consequently, most relevant analytical methods to detect the aromatic amines composition in environmental matrices, and for monitoring their degradation, are essential and will be presented. Those include Spectroscopy, namely UV/visible and Fourier Transform Infrared Spectroscopy (FTIR); Chromatography, in particular Thin Layer (TLC), High Performance Liquid (HPLC) and Gas chromatography (GC); Capillary electrophoresis (CE); Mass spectrometry (MS) and combination of different methods including GC-MS, HPLC-MS and CE-MS. Choosing the best methods depend on their availability, costs, detection limit and sample concentration, which sometimes need to be concentrate or pretreated. However, combined methods may give more complete results based on the complementary information. The environmental impact, toxicity and carcinogenicity of many aromatic amines have been reported and are emphasized in this chapter too. Lately, the conventional aromatic amines degradation and the alternative biodegradation processes are highlighted. Parameters affecting biodegradation, role of different electron acceptors in aerobic and anaerobic biodegradation and kinetics are discussed. Conventional processes including extraction, adsorption onto activated carbon, chemical oxidation, advanced oxidation, electrochemical techniques and irradiation suffer from drawbacks including high costs, formation of hazardous by-products and low efficiency. Biological processes, taking advantage of the naturally processes occurring in environment, have been developed and tested, proved as an economic, energy efficient and environmentally feasible alternative. Aerobic biodegradation is one of the most promising techniques for aromatic amines remediation, but has the drawback of aromatic amines autooxidation once they are exposed to oxygen, instead of their degradation. Higher costs, especially due to power consumption for aeration, can also limit its application. Anaerobic degradation technology is the novel path for treatment of a wide variety of aromatic amines, including industrial wastewater, and will be discussed. However, some are difficult to degrade under anaerobic conditions and, thus, other electron acceptors such as nitrate, iron, sulphate, manganese and carbonate have, alternatively, been tested.

Right coronary artery fistula with congestive heart failure in the neonate. Doppler echocardiographic diagnosis and closure with detachable balloon

We report here a case of coronary artery fistula in a neonate with clinical signs of heart failure. The electrocardiogram showed signs of left ventricular hypertrophy and diffuse alterations in ventricular repolarization. Chest X-ray showed an enlargement of the cardiac silhouette with an increase in pulmonary flow. After echocardiographic diagnosis and angiographic confirmation, closure of the fistulous trajectory was performed with a detachable balloon with an early and late successful outcome.

Persistent organic chemicals of emerging environmental concern

The use of chemicals and chemical derivatives in agriculture and industry has contributed to their accumulation and persistence in the environment. Persistent organic pollutants (POPs) are among the environmental pollutants of most concern since, when improperly handled and disposed, they can persist in the environment, bioaccumulate through the food web, and may create serious public health and environmental problems. Development of an effective degradation process has become an area of intense research. The physical/chemical methods employed, such as volatilization, evaporation, photooxidation, adsorption, or hydrolysis, are not always effective, are very expensive, and, sometimes, lead to generation/disposal of other contaminants. Biodegradation is one of the major mechanisms by which organic contaminants are transformed, immobilized, or mineralized in the environment. A clear understanding of the major processes that affect the interactions between organic contaminants, microorganisms, and environmental matrix is, thus, important for determining persistence of the compounds, for predicting in situ transformation rates, and for developing site remediation. Information on their risks and impact and occurrence in the different environmental matrices is also important, in order to attenuate their impact and apply the appropriate remediation process. This chapter provides information on the fate of pesticides and polycyclic aromatic hydrocarbons (PAHs), their impact, bioavailability, and biodegradation. © Springer Science+Business Media Dordrecht 2014.

Association of pulmonary atresia with intact ventricular septum and aortic valve stenosis. Prenatal diagnosis

A rare association of pulmonary atresia with an intact septum was diagnosed through echocardiography in a fetus 32 weeks of gestational age. The diagnosis was later confirmed by echocardiography of the newborn infant and further on autopsy. The aortic valve was bicuspid with a pressure gradient of 81mmHg, and the right ventricle was hypoplastic, as were the pulmonary trunk and arteries, and the blood flow was totally dependent on the ductus arteriosus.

Ebstein's anomaly with imperforate tricuspid valve. Prenatal diagnosis

Ebstein's anomaly is an uncommon congenital heart defect, with a prevalence of 0.3-0.5%. Its association with an imperforate tricuspid valve is an even more rare situation (less than 10% of cases). Prenatal diagnosis of this association by means of fetal echocardiography has not been reported. We describe here this association diagnosed before birth and confirmed after birth. The diagnostic potential and importance of fetal echocardiography during prenatal evaluation of cardiac malformations allows for adequate perinatal planning and management, with an obvious impact on morbidity and mortality.