Distribution of two splice variants of the glutamate transporter GLT-1 in rat brain and pituitary

We have performed immunocytochemistry on rat brains using a highly specific antiserum directed against the originally described form of the glutamate transporter GLT-1 (referred to hereafter as GLT-1alpha), and another against a C-terminal splice variant of this protein, GLT-1B. Both forms of GLT-1 were abundant in rat brain, especially in regions such as the hippocampus and cerebral cortex, and macroscopic examination of sections suggested that both forms were generally regionally coexistent. However, disparities were evident; GLT-1alpha was present in the intermediate lobe of the pituitary gland, whereas GLT-1B was absent. Similar marked disparities were also noted in the external capsule, where GLT1A labeling was abundant but GLT-1B was only occasionally encountered. Conversely, GLT-1B was more extensively distributed, relative to GLT-1alpha, in areas such as the deep cerebellar nuclei. In most regions, such as the olfactory bulbs, both splice variants were present but differences were evident in their distribution. In cerebral cortex, patches were evident where GLT-1B was absent, whereas no such patches were evident for GLT-1alpha. At high resolution, other discrepancies were evident; double-labeling of areas such as hippocampus indicated that the. two splice variants may either be differentially expressed by closely apposed glial elements or that the two splice variants may be differentially targeted to distinct membrane domains of individual glial cells. (C) 2002 Wiley-Liss, Inc.

Caracterização de regiões encefálicas no cérebro normal por tensor de difusão e aplicação à epilepsia pós-traumática

Mestrado em Radiações Aplicadas às Tecnologias da Saúde.

Atitude relativamente à máquina de café em cápsula: estudo sobre razões de compra

O café é uma das bebidas preferidas dos portugueses. Desde o ano 2010 que assistimos a uma tendência de crescimento no consumo de café no lar, nomeadamente desde o aparecimento de uma maior variedade de máquinas de café em cápsula. A presente dissertação procurou compreender “que aspetos valoriza o comprador de máquina de café em cápsula maior de 18 anos, da cidade de Lisboa, na sua compra?”. As respostas obtidas com este trabalho vão permitir aos profissionais de marketing das empresas comercializadoras das máquinas de café em cápsula conhecer o seu comprador e definir novas estratégias que contribuirão para o sucesso deste produto. Recorrendo a uma abordagem metodológica quantitativa, foi realizado um inquérito por questionário a possuidores de máquina de café em cápsula. Esta investigação aborda o comportamento de compra deste eletrodoméstico, incidindo sobre alguns dos aspetos que influenciam uma atitude favorável na sua compra.

Helical tomotherapy versus 3D conformal radiotherapy in dosimetric planning for patients with localized prostate cancer

Radiotherapy is one of the therapeutics selected for localized prostate cancer, in cases where the tumour is confined to the prostate, penetrates the prostatic capsule or has reached the seminal vesicles (T1 to T3 stages). The radiation therapy can be administered through various modalities, being historically used the 3D conformal radiotherapy (3DCRT). Other modality of radiation administration is the intensity modulated radiotherapy (IMRT), that allows an increase of the total dose through modulation of the treatment beams, enabling a reduction in toxicity. One way to administer IMRT is through helical tomotherapy (TH). With this study we intent to analyze the advantages of helical tomotherapy when compared with 3DCRT, by evaluating the doses in the organs at risk (OAR) and planning target volumes (PTV).

A influência da marca Nespresso no comportamento de compra da máquina e cápsulas de café

Dissertação apresentada à Escola Superior de Comunicação Social como parte dos requisitos para obtenção de grau de mestre em Publicidade e Marketing.

Strategies for price reduction of HIV medicines under a monopoly situation in Brazil

ABSTRACT OBJECTIVE To analyze Government strategies for reducing prices of antiretroviral medicines for HIV in Brazil. METHODS Analysis of Ministry of Health purchases of antiretroviral medicines, from 2005 to 2013. Expenditures and costs of the treatment per year were analyzed and compared to international prices of atazanavir. Price reductions were estimated based on the terms of a voluntary license of patent rights and technology transfer in the Partnership for Productive Development Agreement for atazanavir. RESULTS Atazanavir, a patented medicine, represented a significant share of the expenditures on antiretrovirals purchased from the private sector. Prices in Brazil were higher than international references, and no evidence was found of a relationship between purchase volume and price paid by the Ministry of Health. Concerning the latest strategy to reduce prices, involving local production of the 200 mg capsule, the price reduction was greater than the estimated reduction. As for the 300 mg capsule, the amounts paid in the first two years after the Partnership for Productive Development Agreement were close to the estimated values. Prices in nominal values for both dosage forms remained virtually constant between 2011 (the signature of the Partnership for Productive Development Agreement), 2012 and 2013 (after the establishment of the Partnership). CONCLUSIONS Price reduction of medicines is complex in limited-competition environments. The use of a Partnership for Productive Development Agreement as a strategy to increase the capacity of local production and to reduce prices raises issues regarding its effectiveness in reducing prices and to overcome patent barriers. Investments in research and development that can stimulate technological accumulation should be considered by the Government to strengthen its bargaining power to negotiate medicines prices under a monopoly situation.

Virulence Factors IN Fungi OF Systemic Mycoses

Pathogenic fungi that cause systemic mycoses retain several factors which allow their growth in adverse conditions provided by the host, leading to the establishment of the parasitic relationship and contributing to disease development. These factors are known as virulence factors which favor the infection process and the pathogenesis of the mycoses. The present study evaluates the virulence factors of pathogenic fungi such as Blastomyces dermatitidis, Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum and Paracoccidioides brasiliensis in terms of thermotolerance, dimorphism, capsule or cell wall components as well as enzyme production. Virulence factors favor fungal adhesion, colonization, dissemination and the ability to survive in hostile environments and elude the immune response mechanisms of the host. Both the virulence factors presented by different fungi and the defense mechanisms provided by the host require action and interaction of complex processes whose knowledge allows a better understanding of the pathogenesis of systemic mycoses.

Diterpenos de Copaifera reticulata Ducke com atividade larvicida contra Aedes aegypti (L.) (Diptera, Culicidae)

The objective of this study was to evaluate the larvicidal activity of diterpenoids obtained from the oil-resin of Copaifera reticulata against Aedes aegypti larvae, the principal vector of dengue and urban yellow fever. Four diterpenes were obtained from oil-resin extraction with organic solvents and subsequent chromatographic and spectroscopic procedures allowed to isolation and identification of these compounds as 3-b-acetoxylabdan-8(17)-13-dien-15-oic acid (1), alepterolic acid (2), 3-b-hidroxylabdan-8(17)-en-15-oic acid (3), and ent-agatic acid (4). Each compound was previously dissolved in dimethylsulphoxide, and distilled water was added to obtain the desired concentrations. Twenty larvae of third instars were placed into plastic beckers, containing the solution test (25 mL), in a five repetitions scheme, and their mortality, indicated by torpor and darkening of the cephalic capsule, was recorded after 48h. Probit analyses were used to determine lethal concentrations (LC50 and LC90) and their respective 95% confidence intervals. This study showed that only diterpenoids 1 and 2 exhibited larvicidal properties with LC50 of 0.8 ppm and 87.3 ppm, respectively, revealing the former as the most toxic compound against third instars of Ae. aegypti. Therefore, this compound seems to be an interesting source for new metabolite to be exploited.

Genotypic characterization of virulence factors in Escherichia coli strains from patients with cystitis

Adhesins (P-fimbriae, S-fimbriae, type 1 fimbriae and afimbrial adhesin), toxins (α-hemolysin and cytotoxic necrotizing factor type 1), iron acquisition systems (aerobactin) and host defense avoidance mechanisms (capsule or lipopolysaccharide) have been shown to be prevalent in Escherichia coli strains associated with urinary tract infections. In this work, 162 Uropathogenic Escherichia coli (UPEC) strains from patients with cystitis were genotypically characterized by polymerase chain reaction (PCR) assay. We developed three multiplex PCR assays for virulence-related genes papC, papE/F, papG alleles, fimH, sfa/foc, afaE, hly, cnf-1, usp, cdtB, iucD, and kpsMTII, all of them previously identified in UPEC strains. The PCR assay results identified 158 fimH (97.5%), 86 kpsMTII (53.1%), 53 papC/papEF/papG (32.7%), 45 sfa (27.8%), 42 iucD (25.9%), 41 hly (25.3%), 36 usp (22.2%), 30 cnf-1(18.5%) and 10 afa (6.2%) strains. No strain was positive for cdtB. In this work, we also demonstrated that adhesins may be multiple within a single strain and that several virulence genes can occur combined in association.

Histopathology, serology and cultures in the diagnosis of cryptococcosis

Cryptococcosis is one of the most common opportunistic fungal infections in patients with acquired immunodeficiency syndrome (AIDS). We report 13 cases of cryptococcal infection based on histopathology, serology and cultures. Epidemiological analysis, histochemical techniques of hematoxilin and eosin (HE) and Grocot's silver (GMS), as well special histochemical techniques such as Mayer's mucicarmine (MM) and Fontana-Masson (FM), cryptococcal antigen test (CrAg) and isolation on fungal media: Sabouraud's (SAB), brain-heart infusion agar (BHI) and canavanine-glycine-bromothymol blue (CGB) agar were analyzed. Unsatisfactory staining results by MM stain associated to negative titers by CrAg test, which FM stain confirmed that capsule-deficient Cryptococcus infections were observed in four cases. Eight isolated cases were identified as follows: six cases were infection with Cryptococcus neoformans and two cases were Cryptococcus gattii.

Appendiceal Mucocele – Unexpected Diagnosis in a Gynecology Department

Appendiceal mucocele is a rare entity, occuring in < 1% among appendicectomies, with a female predominance 4/1 (F/M) and a mean age of more than 50 years. The preoperative diagnosis is difficult; in most cases, it´s an intraoperative finding. In such work, we describe the two clinical cases occurring in last 10 years in our Department. Case 1 - 56 years old, posmenopausal, referred to our Department (02/2004) because an asymptomatic right adnexal septated cystic image, 53x48mm, with hipovascularized septa and a vascularised capsule with low flow resistance (IR 0,57). CA 125 elevated (71,3 U/mL).Exploratory laparotomy: an ovary increased, with a gelatanious consistency and an appendicular enlargement. Extemporaneous examination: a pseudomixoma peritonei, associated with a mucinous appendicular and an ovary tumor. It was performed a radical surgery. The histo-pathological analysis showed a mucinous cystadenoma of the appendix with peritoneal mucinous dissemination involving the ovary. Expectant attitude since the surgery, without clinical and imaging signs of recurrence. Case 2- 62 years old posmenopausal and asymptomatic woman, with a large adnexal mass detected on routine pelvic ultrasound: heterogeneous, 94x84mm without vascularisation signs in its interior. CEA was elevated (41,47U/ml). Exploratory laparotomy (02/2010): enlarged appendix and macroscopically normal pelvic organs. An appendicectomy was performed. The histo-pathological analysis showed a 10cm mucinous cystadenoma of the appendix and signs of localized (visceral peritoneal surface) pseudomyxoma peritonei. Currently she’s clinically well, in an expectant attitude. Despite mucoceles of the appendix are rare, they should be considered in women presenting with abnormal quadrant masses.

USE OF LOPINAVIR/RITONAVIR ASSOCIATED WITH ERGOTAMINE RESULTING IN FOOT AMPUTATION: BRIEF COMMUNICATION

A 32-year-old female, was diagnosed in 2004 with a C1 HIV1 infection, using zidovudine/lamivudine 300/150 mg BID and lopinavir/ritonavir 400/100 mg BID, in addition to prophylaxis with trimethoprim-sulfamethoxazole 800/160 mg QD, but no prophylaxis with macrolide antibiotics. The patient presented with a severe headache and was prescribed two capsules of the anti-migraine drug Ormigrein™, which contained ergotamine tartrate 1 mg, caffeine 100 mg, paracetamol 220 mg, hyoscyamine sulfate 87.5 mcg, and atropine sulfate 12.5 mcg. Afterwards she was prescribed one capsule of Ormigrein every 30 minutes for a total of six capsules a day. The patient took the medication as prescribed but developed a pain in her left ankle three days later, which evolved to the need for amputation.

Understanding the relationship between central metabolism and virulence in the human pathogen Streptococcus pneumoniae

Dissertation presented to obtain the Ph.D. degree in Biochemistry

EVALUATION OF SUBLETHAL EFFECTS OF Ipomoea cairica LINN. EXTRACT ON LIFE HISTORY TRAITS OF DENGUE VECTORS

Plant derived insecticides have considerable potential for mosquito control because these products are safer than conventional insecticides. This study aimed to investigate sublethal activities of Ipomoea carica or railway creeper crude acethonilic extract against life history trait of dengue vectors, Aedes albopictus and Aedes aegypti. The late third instar larvae of Ae. albopictus and Ae. aegypti were exposed to a sublethal dose at LC50 and larvae that survived were further cultured. Overall, Ipomea cairica crude extracts affected the whole life history of both Aedes species. The study demonstrated significantly lower egg production (fecundity) and eggs hatchability (fertility) in Ae. albopictus. The sublethal dose of crude extracts reduced significantly the width of larval head capsule and the wing length of both sexes in both Aedes species. The significance of sublethal effects of I. cairica against Aedes mosquitoes was an additional hallmark to demonstrate further activity of this plant despite its direct toxicity to the larvae. The reduced reproductive capacity as well as morphological and physiological anomalies are some of the effects that make I. cairica a potential candidate to be used as a new plant-based insecticide to control dengue vectors.

IgG4-Related Hashimoto's Thyroiditis - A New Variant of a Well Known Disease

Hashimoto's thyroiditis (HT) has been characterized for many years as a well-defined clinicopathologic entity, but is now considered a heterogeneous disease. IgG4-related HT is a new subtype characterized by thyroid inflammation rich in IgG4-positive plasma cells and marked fibrosis. It may be part of the systemic IgG4-related disease. We report a case of a 56-year-old Portuguese man who presented with a one-month history of progressive neck swelling and dysphagia. Laboratory testing revealed increased inflammatory parameters, subclinical hypothyroidism and very high levels of thyroid autoantibodies. Cervical ultrasound (US) demonstrated an enlarged and heterogeneous thyroid gland and two hypoechoic nodules. US-guided fine needle aspiration cytology was consistent with lymphocytic thyroiditis. The patient was submitted to total thyroidectomy and microscopic examination identified typical findings of HT, marked fibrosis limited within the thyroid capsule and lymphoplasmacytic infiltration, with >50 IgG4-positive plasma cells per high-power field and an IgG4/IgG ratio of >40%. After surgery, serum IgG4 concentration was high-normal. Symptoms relief and reduction in laboratory inflammatory parameters were noticed. Thyroid function is controlled with levothyroxine. To our knowledge we report the first case of IgG4-related HT in a non-Asian patient. We also perform a review of the literature regarding IgG4-related disease and IgG4-related HT. Our case highlights this new variant of the well known HT, and helps physicians in recognizing its main clinical features, allowing for proper diagnosis and treatment.