Otimização do perfil farmacocinético e farmacodinâmico de fármacos anticancerígenos através da sua veiculação em nanossistemas lipídicos

Dissertação de mestrado em Biofísica e Bionanossistemas

O método potenciométrico na determinação do H+ trocável em solos

For the determination of exchangeable hydrogen ion in soils, the authors of the presente work made the extraction with normal calcium acetate solution that may have an initial pH between 7 and 8 without altering the amount of hydrogen ion extracted. The extraction was made by shaking 5,0 grams of air dry soil with 100 ml of normal calcium acetate solution, the pH of wich was ascertained to 7,0, 7,5 and 8,0 with acetic acid, in 250 mil conical flasks for 30 minutes in a Wagner shaker (30-40 rpm). The contents of the flasks were then, filtered. A 50 ml aliquot of each of the leachate was titrated with a 0,020 N NaOH solution and the volumes consumed sodium hydroxide were ploted against pH. The titration curves thus obtained showed to be straight lines between pH 8 and 9 and parallel to the curve obtained by the titration of the blank. Two ways of locating the end point of the titration showed to be possible: the use of a pHmeter or titrimeter or the use of phenolphtalein as indicator. When using a pH meter or a titrimeter, the end point may rest in any point between pH 8 and 9, and the volume of sodium hydroxide consumed is found by comparison with a similar curve obtained by the titration of the blank. When using phenolphtalein the calcium acetate solution must have a pH below 8.

A new species of Stratiodrilus (Polychaeta, Histriobdellidae) from freshwater crayfishes of southern Brazil

A new species of polychaete, Stratiodrilus vilae, epizoic on Parastacus brasiliensis (von Martens, 1869) and P. defossus Faxon, 1898, is described from the State of Rio Grande do Sul, southern Brazil. The new species has one pair of long, anal, conical ventral lobes, one on each side of the anus, claspers in the males, and one pair of tubercles in each of the posterior locomotor appendages; and the jaw apparatus not reaching the limit between the head and the first segment.

New species of Cyclodontina from Bahia, Brazil (Gastropoda, Pulmonata, Odontostomidae)

A new species of pulmonate snail was recently collected in a small forest fragment in the city of Bom Jesus da Lapa, Bahia state, Brazil. Bahia is known for a high diversity of land snails and Bom Jesus da Lapa is an interesting locality, since it is close to the interface between two major Brazilian biomes: Cerrado and Caatinga. The new species is described as Cyclodontina tapuia sp. nov. and can be easily identified by its brown shell, conical spire, convex whorls, a sculpture comprised of strong ribs, and an aperture with four barriers: a median parietal tooth, a median palatal tooth, a median basal tooth and a strong columellar lamella. This discovery is also a reminder of how little the Brazilian continental molluscan fauna is known and of the urgency in studying and preserving the rich (though usually overlooked) fauna of the Caatinga.

Firm Size and Short-Term Dynamics in Aggregate Entry and Exit

Much of the research on industry dynamics focuses on the interdependence between the sectorial rates of entry and exit. This paper argues that the size of firms and the reaction-adjustment period are important conditions missed in this literature. I illustrate the effects of this omission using data from the Spanish manufacturing industries between 1994 and 2001. Estimates from systems of equations models provide evidence of a conical revolving door phenomenon and of partial adjustments in the replacement-displacement of large firms. KEYWORDS: aggregation, industry dynamics, panel data, symmetry, simultaneity. JEL CLASSIFICATION: C33, C52, L60, L11

Physa Marmorata Guilding, 1828 (Pulmonata: Physidae)

A description of Physa marmorata Guilding, 1828, based on material collected at its type-locality, the Caribbean island of Saint Vincent, is presented. The shell is thin, horn-colored, surface very glossy, diaphanous. Spire acute, elevated; protoconch distinct, rounded-conical, reddish-brown; five not shouldered, broadly convex whorls with subobsolete spiral lines and thin growth lines. Aperture elongated, 1.4-2.0 times as long as the remaining shell length, narrow obovate-lunate; upper half acute-angled,lower half oval,narrowly rounded at the base, outer lip sharp, inner lip completely closing the umbilical region; a very distinct callus on the parietal wall; columellar lip with a low ridge gradually merging into the callus. ratios: shell width/shell length = 0.44 - 0.52 (mean 0.47); spire length /shell lenght = 0.33-0.41 (mean 0.39); aperture length/shell lenght = 0.59-0.67 (mean 0.62). Oral lappets laterally mucronate, foot spatulate with deeply pigmented acuminate tail. Mantle reflection with 6-10 short triangular dentations covering nearly half the right surface of the body whorl, and 4-6 covering a part of the ventral wall. Body surface with tiny dots of greenish-yellow pigment besides melanin. Renal tube tightly folded in toa zigzag course. Ovotestis diverticula acinous, laterally pressed against each other around a collecting canal. Ovispermiduct with well-developed seminal vesicle. oviduct highly convoluted, merging into a less convoluted nidamental gland which narrows to a funnel-shaped uterus and a short vagina. Spermathecal body oblong, more or less constricted in the middle and somewhat curved; spermathecal duct uniformly narrow, a little longer than be body. About 20 prostatic diverticula, simple, bifurcate or divided into a few short branches, distalmost ones assembled into a cluster. Penis long, nearly uniformly narrow; penial canal with lateral opening about the junction of its middle and lower thirds. Penial sheath with a bulbous terminal expasion the tip of which isinserted into the caudal end of the prepuce. Prepuce shouldered, much wider than the narrow portion of the penial sheath. Penial sheath/prepuce ratio about 2.08 (1.45-2.75). The main extrinsic muscles of the penial complex are a retractor, with a branch attached to the bulb, and another to the caudal end of the penial sheath; and a protractor, with a branch attached to the shoulder of the prepuce and adjoining area of the penial sheath, and another to the caudal end of the penial sheath. Egg capsule C-shaped, with 10-30 elliptical eggs (snails 10mm long) measuring about 1.10 mm (0.90-1.32) through the long axis and surrounded by an inner and an outer lamellate membranes. Jaw a simple obtusely V-shaped plate. radula will be described separately.

Physa cubensis Pfeiffer, 1839 (Pulmonata: Physidae)

A description of Physa cubensis Pfeiffer, 1839, based on 15 speciments collected in Havana, Cuba, is presented. The shell, measuring 9.0 x 4,8mm to 12.3 x 6.4mm, is ovate-oblong, thin, diaphanous, horncolored, shining. Spire elevated, broadly conical; protoconch distinct, roundish, reddish-brown. About five moderately shouldered, roundly convex whorls, penultimate whorl expanded; spiral striation subobsolete; growth line faint on the intermediate whorls, clearly visible on the body whorl, crowded here and there. Suture well impressed. Aperture elongated 2.05 - 2.67 (mean 2.27) times as long as the remaining length of the shell, narrow obovulate-lunate; upper half acute-angled, lower half oval, narrowly rounded at the base; outer lip sharp, inner lip completely closing the umbilical region; a thick callus on the parietal wall; columellar plait well marked. Ratios: shell width/shell length - 0.52-0.61 (mean 0.55); spire length/shell length = 0.27 - 0.33 (mean 0.31); aperture length/shell length = 0.67 - 0.73 (mean 0.69). Oral lappets laterally mucronate; foot spatulate with acuminate tail. Mantle relection with 6 - 8 short triangular dentations in the right lobe (columellar side) and 4 - 6 in the left lobe (near the pneumostome). Renal tube tightly folded into a zigzag course. Ovotestis, ovispermiduct, seminal vesicle, oviduct, nidamental gland, uterus and vagina as in Physa marmorata (see Paraense, 1986, Mem. Inst. Oswaldo Cruz, 81: 459-469). Spermathecal body egg-shaped or pear-shaped; spermathecal ducta uniformly narrow with expanded base, a little longer than the body. Spermiduct, prostate and vas deferens as in P. marmorata (Paraense, loc. cit.). Penis wide proximally, narrowing gradually apicad; penial canal with subterminal outlet. Penial sheath following the width of the penis and ending up by a bulbous expansion somewhat narrower than the proximal portion. Penaial sheath/prepuce ration = 1,25 - 1,83 (mean 1.49). Prepuce much wider than the bulb of the penial shealth, moderately shouldered owing to the intromission of the bulb, and with a large gland in one side of its proximal half occupating about a third of its length. Extrinsic muscles of the penial complex as in P. marmorata. Jaw a simple obtusely V-shaped plate. Radula to be described separetely.

Homotopy limits for 2-categories

We study homotopy limits for 2-categories using the theory of Quillen model categories. In order to do so, we establish the existence of projective and injective model structures on diagram 2-categories. Using these results, we describe the homotopical behaviour not only of conical limits but also of weighted limits. Finally, pseudo-limits are related to homotopy limits.

Fum i miralls: trobant l'ordre en un món caòtic

El calidoscopi és una joguina que converteix fragments de vidre acolorit en patrons infinitament variats mitjançant l'ús de miralls. Hi ha quelcom satisfactori en els patrons –els necessitem per crear significat, i trobem bellesa en la seva simetria. No obstant, els sistemes complexos desobeeixen les fórmules simples. Per exemple, és impossible descriure una cosa tan prosaica com el comportament del fum mentre ascendeix fent servir les matemàtiques clàssiques. Agafant en préstec idees de diferents disciplines, podem considerar l'alfabetització informacional com una invitació per als nostres estudiants per jugar amb la imprevisible varietat de l'experiència humana i descobrir patrons que els resultin plens de significat.

Nitric oxide synthase 2 is required for conversion of pro-fibrogenic inflammatory CD133+ progenitors into F4/80+ macrophages in experimental autoimmune myocarditis.

AIMS: Experimental autoimmune myocarditis (EAM) model mirrors important mechanisms of inflammatory dilated cardiomyopathy (iDCM). In EAM, inflammatory CD133(+) progenitors are a major cellular source of cardiac myofibroblasts in the post-inflammatory myocardium. We hypothesized that exogenous delivery of macrophage-colony-stimulating factor (M-CSF) can stimulate macrophage lineage differentiation of inflammatory progenitors and, therefore, prevent their naturally occurring myofibroblast fate in EAM. METHODS AND RESULTS: EAM was induced in wild-type (BALB/c) and nitric oxide synthase 2-deficient (Nos2(-/-)) mice and CD133(+) progenitors were isolated from inflamed hearts. In vitro, M-CSF converted inflammatory CD133(+) progenitors into nitric oxide-producing F4/80(+) macrophages and prevented transforming growth factor-β-mediated myofibroblast differentiation. Importantly, only a subset of heart-infiltrating CD133(+) progenitors expresses macrophage-specific antigen F4/80 in EAM. These CD133(+)/F4/80(hi) cells show impaired myofibrogenic potential compared with CD133(+)/F4/80(-) cells. M-CSF treatment of wild-type mice with EAM at the peak of disease markedly increased CD133(+)/F4/80(hi) cells in the myocardium, and CD133(+) progenitors isolated from M-CSF-treated mice failed to differentiate into myofibroblasts. In contrast, M-CSF was not effective in converting CD133(+) progenitors from inflamed hearts of Nos2(-/-) mice into macrophages, and M-CSF treatment did not result in increased CD133(+)/F4/80(hi) cell population in hearts of Nos2(-/-) mice. Accordingly, M-CSF prevented post-inflammatory fibrosis and left ventricular dysfunction in wild-type but not in Nos2(-/-) mice. CONCLUSION: Active and NOS2-dependent induction of macrophage lineage differentiation abrogates the myofibrogenic potential of heart-infiltrating CD133(+) progenitors. Modulating the in vivo differentiation fate of specific progenitors might become a novel approach for the treatment of inflammatory heart diseases.

Altering in vivo fate of heart-infiltrating progenitors from pro-fibrotic into F4/80+macrophages prevents progression of myocarditis into inflammatory dilated cardiomyopathy

Rationale: Experimental autoimmune myocarditis (EAM) mirrors important pathogenic aspects of inflammatory cardiomyopathy, a common cause of heart failure. In EAM, TGF-β-dependent conversion of heart-infiltrating prominin-1+ progenitors into myofibroblasts is critical for development of fibrosis and the end-stage heart failure phenotype. Therapeutic strategies modulating the in vivo fate of prominin-1+ progenitors might therefore prevent TGF-β-mediated cardiac fibrosis and pathological remodelling. Methods and Results: EAM was induced in BALB/c mice using alpha-myosin heavy chain (aMyHC) peptide/complete Freund's adjuvant (CFA) immunization. Prominin-1+ cells were isolated from the inflamed hearts at day 21 after immunization, expanded and treated with Macrophage Colony-Stimulating Factor (M-CSF) or Transforming Growth Factor-beta (TGF-β). Herein, we demonstrated that M-CSF turns, ex vivo and in the EAM, heart-infiltrating prominin-1+ progenitors into immunosuppressive F4/80/CD11b/CD16/32/NOS2-expressing, nitric oxide producing and E.coli bacteria phygocyting macrophages, and protect further TGF-β-stimulated differentiation into pathogenic myofibroblasts. Systemic M-CSF treatment during myocarditis completely prevented post-inflammatory fibrosis, T cell relapse and left ventricular dysfunction. Mechanistically, M-CSF-induced macrophage differentiation from prominin-1+ progenitors critically required nitric oxide synthase 2. Accordingly, M-CSF treatment failed to reduce myocardial fibrosis development in Nos2-/- mice. Conclusions: Altering the in vivo fate of inflammatory prominin-1 expressing progenitors from pro-fibrotic into the F4/80 expressing macrophage phenotype protects from myocarditis progression, cardiac fibrosis, and heart failure. These findings offer a modern therapeutic model and challenge former concepts, which attributed macrophages a detrimental role in inflammatory cardiomyopathy progression.

Binema bonaerensis n. sp. (Oxyurida: Thelastomatidae) parasite of Neocurtilla claraziana saussure (Orthoptera: Gryllotalpidae) in Argentina

The nematode Binema bonaerensis n. sp. (Oxyurida: Thelastomatidae) is described from the intestine of the mole cricket of Neocurtilla claraziana Saussure (Orthoptera: Gryllotalpidae) from Buenos Aires Province, Argentina. It is distinguished mainly by having a conical tail; three sclerotized arches in the buccal cavity; an excretory pore inmediately posterior to the base of the esophagus and the presence of five pairs of male genital papillae with one pair preanal and four pairs postanal.

Caracterización de materiales en banda W

Para medir los coeficientes de transmisión y reflexión, S21 y S11, de diferentes materiales o muestras planas, se usa un sistema de toma de medidas en espacio libre operando banda W (75 – 110 GHz). Usando estos parámetros, S21 y S11, podemos calcular la permitividad dieléctrica relativa compleja (Er ) y la permeabilidad magnética relativa compleja (μr) mediante un proceso llamado NRW (Nicolson-Ross-Weir). El sistema para medir consiste en dos antenas de bocina, una transmisora y otra receptora, dos espejos con los que obtenemos una onda plana para medir las propiedades del material y un ordenador o dispositivo que calcula los resultados. Este dispositivo requiere de calibración para la obtención de resultados óptimos. Dicho sistema se puede simular de manera ideal con un software llamado ADS (Assistance Design System) para el estudio y comparación de grosores, permitividades dieléctricas relativas y permeabilidades magnéticas relativas de los materiales en función de la frecuencia.

Copeptin, a stable peptide derived from the vasopressin precursor, correlates with the individual stress level.

BACKGROUND: During stress, vasopressin is a potent synergistic factor of CRH as a hypothalamic stimulator of the HPA axis. The measurements of CRH and vasopressin levels are cumbersome because of their instability and short half-life. Copeptin is a more stable peptide stoichiometrically released from the same precursor molecule. The aim of our study was to compare copeptin and cortisol levels in different stress situations. METHODS: Three groups of patients with increasing stress levels were investigated: a) healthy controls without apparent stress (n=20), b) hospitalized medical patients with moderate stress (n=25) and c) surgical patients 30 minutes after extubation, with maximal stress (n=29). In all patients we assessed cortisol and copeptin levels. Copeptin levels were measured with a new sandwich immunoassay. RESULTS: Cortisol levels in controls were (median, IQ range, 486 [397-588] nmol/L), not significantly different as compared to medical patients (438 [371-612] nmol/L, p=0.69). Cortisol levels in surgical patients after extubation were higher (744 [645-1062] nmol/L p<0.01 vs controls and medical patients). Copeptin levels in controls were 4.3 [3.2-5.5] pmol/L, which was lower as compared to medical patients (17.5 [6.4-24.1], p<0.001) and surgical patients after extubation (67.5 [37.8-110.0] pmol/L, p<0.001). The correlation between copeptin levels and cortisol was r=0.46, p<0.001. CONCLUSION: Copeptin is a novel marker of the individual stress level. It more subtly mirrors moderate stress as compared to cortisol values.

X-ray microtomography of Larger Foraminifera

X-ray microtomography has become a new tool in earth sciences to obtain non-destructive 3D-image data from geological objects in which variations in mineralogy, chemical composition and/or porosity create sufficient x-ray density contrasts.We present here first, preliminary results of an application to the external and internal morphology of Permian to Recent Larger Foraminifera. We use a SkyScan-1072 high-resolution desk-top micro-CT system. The system has a conical x-ray source with a spot size of about 5µm that runs at 20-100kV, 0-250µA, resulting in a maximal resolution of 5µm. X-ray transmission images are captured by a scintillator coupled via fibre optics to a 1024x1024 pixel 12-bit CCD. The object is placed between the x-ray source and the scintillator on a stub that rotates 360°around its vertical axis in steps as small as 0.24 degrees. Sample size is limited to 2 cm due to the absorption of geologic material for x-rays. The transmission images are back projected using a Feldkamp algorithm into a vertical stack of up to 1000 1Kx1K images that represent horizontal cuts of the object. This calculation takes 2 to several hours on a Double-Processor 2.4GHz PC. The stack of images (.bmp) can be visualized with any 3D-imaging software, used to produce cuts of Larger Foraminifera. Among other applications, the 3D-imaging software furnished by SkyScan can produce 3D-models by defining a threshold density value to distinguish "solid" from "void. Several models with variable threshold values and colors can be imbricated, rotated and cut together. The best results were obtained with microfossils devoid of chamber-filling cements (Permian, Eocene, Recent). However, even slight differences in cement mineralogy/composition can result in surprisingly good x-ray density contrasts.X-ray microtomography may develop into a powerful tool for larger microfossils with a complex internal structure, because it is non-destructive, requires no preparation of the specimens, and produces a true 3D-image data set. We will use these data sets in the future to produce cuts in any direction to compare them with arbitrary cuts of complex microfossils in thin sections. Many groups of benthic and planktonic foraminifera may become more easily determinable in thin section by this way.