Electrochemical sensor highly selective for estradiol valerate determination based on a modified carbon paste with iron tetrapyridinoporphyrazine

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Selective Ablation of the Androgen Receptor in Mouse Sertoli Cells Affects Sertoli Cell Maturation, Barrier Formation and Cytoskeletal Development

The observation that mice with a selective ablation of the androgen receptor (AR) in Sertoli cells (SC) (SCARKO mice) display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli) and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin). Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2). It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.

The selective neurotoxin DSP-4 impairs the noradrenergic projections from the locus coeruleus to the inferior colliculus in rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Renal effects of angiotensin II receptor subtype 1 and 2-selective ligands injected into the paraventricular nucleus of conscious rats

We determined the effects of losartan and CGP42112A (selective ligands of the AT1 and AT2 angiotensin receptors, respectively) and salarasin (a relatively nonselective angiotensin receptor antagonist) on urinary volume and urinary sodium and potassium excretion induced by administration of angiotensin II (ANG II) into the paraventricular nucleus (PVN) of conscious rats. Both the AT1 and AT2 ligands and salarasin administered in the presence of ANG II elicited a concentration-dependent inhibition of urine excretion, but losartan inhibited only 75% of this response. The IC50 for salarasin, CGP42112A, and losartan was 0.01, 0.05, and 6 nM, respectively. Previous treatment with saralasin, CGP42112A and losartan competitively antagonized the natriuretic responses to PVN administration of ANG II, and the IC50 values were 0.09, 0.48, and 10 nM, respectively. The maximum response to losartan was 65% of that obtained with saralasin. Pretreatment with saralasin, losartan, and CGP42112A injected into the PVN caused shifts to the right of the concentration-response curves, but the losartan concentrations were disproportionately greater compared with salarasin or CGP42112A. The IC50 values were 0.06, 0.5, and 7.0 for salarasin, CGP42112A, and losartan, respectively. These results suggest that both AT1 and AT2 receptor subtypes in the PVN are involved in ANG II-related urine, sodium, and potassium excretion, and that the inhibitory responses to AT2 blockade are predominant. Copyright (C) 1999 Elsevier Science B.V.

Structure of thrombin complexed with selective non-electrophilic inhibitors having cyclohexyl moieties at P1

The crystal structures of five new non-electrophilic β-strand-templated thrombin active-site inhibitors have been determined bound to the enzyme. Four co-crystallize with hirugen and inhibitor isomorphously to produce thrombin-hirugen crystals (monoclinic, space group C2), while one co-crystallizes in the hexagonal system, space group P65. A 1,4-substituted cyclohexyl moiety is conserved at the P1 position of all the inhibitors, along with a fused hetero-bicyclic five- and six-membered ring that occupies the P2 site. Amino, amidino and aminoimidazole groups are attached to the cyclohexyl ring for recognition at the S1 specificity site, while benzylsulfonyl and diphenyl groups enhance the binding at the S3 subsite. The cyclohexyl groups at the P1 positions of three of the inhibitors appear to be in the energetically favored chair conformation, while the imidazole-substituted cyclohexyl rings are in a boat conformation. Somewhat unexpectedly, the two cyclohexyl-aminoimidazole groups bind differently in the specificity site; the unique binding of one is heretofore unreported. The other inhibitors generally mimic arginyl binding at S1. This group of inhibitors combines the nonelectrophilicity and selectivity of DAPA-like compounds and the more optimal binding features of the S1-S3 sites of thrombin for peptidic molecules, which results in highly potent (binding constants 12 nM-16 pM, one being 1.1 μM) and selective (ranging from 140 to 20 000 times more selective compared with trypsin) inhibitors of thrombin. The binding modes of these novel inhibitors are correlated with their binding constants, as is their selectivity, in order to provide further insight for the design of therapeutic antithrombotic agents that inhibit thrombin directly at the active site.

Selective factors involved in oil flotation isolation of black yeasts from the environment

The oil flotation isolation technique has been successfully applied to recover chaetothyrialean black yeasts and relatives from the environment. The selective mechanisms playing a role in isolation are unknown. The fungi concerned are supposed to occupy specialized microniches in nature, taking advantage of (1) oligotrophism. Mineral oil as a main selective agent may be based on (2) hydrophobicity or on (3) assimilation. All three hypotheses are tested in this paper. Results show that cell wall hydrophobicity is unlikely to be a selective factor. Incubation under poor nutrient conditions provides competitive advantage for black yeasts, especially for Exophiala strains, which are subsequently enriched by mineral oil which enhances growth in this group of fungi. Incubation under mineral media and mineral oil can be used as selective factor.

Semi-selective culture medium for Xanthomonas axonopodis pv. malvacearum detection in cotton seeds (Gossypium hirsutum L.)

The cotton disease known as angular leaf spot, caused by Xanthomonas axonopodis pv. malvacearum (Xam) has been causing cotton losses in several producing regions around the world. Xam is transmitted by seeds, which may be infected both externally and internally. Infected seeds constitute the main long-distance dissemination mode of the pathogen. In view of this, the use of healthy seeds is a must. To accomplish that, detection methodologies for the bacteria must be developed be used in seed health analysis laboratories. This study aimed to develop a semi-selective medium for Xam detection in cotton seeds. The semi-selective culture medium was named MSSXAN and it was consisted of peptone (5.0 g), beef extract (3 g), sucrose (5 g), soluble starch (10 g), agar (15 g), CaCl 2 (0.25 g), Tween 80 (10 mL), distilled water (1,000 mL), crystal violet solution at 1% (150 μL), cephalexin (50 mg 1*), methyl thyophanate (10 mg*) and chlorothalonil (10 mg*) - *added after culture medium autoclaving. This MSSXAN medium shows low repressiveness to Xam and it be used for isolation of this bacteria in cotton seeds health analysis. © 2009 Academic Journals Inc.

Selective current compensators based on the conservative power theory

This paper presents possible selective current compensation strategies based on the Conservative Power Theory (CPT). This recently proposed theory, introduces the concept of complex power conservation under non-sinusoidal conditions. Moreover, the related current decompositions results in several current terms, which are associated with a specific physical phenomena (power absorption P, energy storage Q, voltage and current distortion D). Such current components are used in this work for the definition of different current compensators, which can be selective in terms of minimizing particular disturbing effects. The choice of one or other current component for compensation directly affects the sizing and cost of active and/or passive devices and it will be demonstrated that it can be done to attend predefined limits for harmonic distortion, unbalances and/or power factor. Single-phase compensation strategies will be discussed by means of the CPT and simulation results will demonstrate their performance. © 2009 IEEE.

Development and application of a highly selective biomimetic sensor for detection of captopril, an important ally in hypertension control

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Treatment of experimental periodontal disease by a selective inhibitor of cyclooxygenase-2 with scaling and root planing (SRP)

Lumiracoxib is a selective inhibitor of cyclooxygenase-2 (COX-2) approved for the relief of symptoms of chronic inflammatory conditions. The aim of this study was to evaluate the effects of this specific inhibitor of COX-2 as adjunctive treatment on induced periodontitis in rats. Periodontal disease was induced at the first mandibular molar of 60 rats. After 7 days, the ligature was removed and all animals were submitted to scaling and root planing (SRP) along with local irrigation with saline solution and were divided into 2 groups: SRP (n = 30)-received subcutaneous injections of 1 mg/kg of body weight/day of saline solution for 3 days and; SRP + L (n = 30)-received subcutaneous injections of 1 mg/kg of body weight/day of Lumiracoxib for 3 days. Ten animals in each group were killed at 7, 15, and 30 days. The histological description was performed and the histometric values were statistically analyzed. In Group SRP + L, the histometric analysis (0.58 ± 0.08, 0.64 ± 0.06, and 0.56 ± 0.10 mm 2) showed less bone loss (p < 0.05) than Group SRP (1.52 ± 0.08, 1.55 ± 0.09, and 1.49 ± 0.24 mm 2) at 7, 15, and 30 days, respectively. Within the limits of this study it can be concluded that subcutaneous application of specific inhibitor of COX-2 was a beneficial adjunctive treatment for periodontal diseases induced in rats. © 2010 Springer Basel AG.