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STUDY QUESTION: Is the expression of steroidogenic enzyme 17α-Hydroxylase/17,20-Lyase (CYP17A1) down-regulated in Leydig cells (LCs) of men with spermatogenic failure and compensated impairment of LC function, i.e. a low testosterone to LH (T/LH) ratio? SUMMARY ANSWER: Although the transcriptional expression of CYP17A1 is increased, its protein expression is decreased, in isolated LCs of men with spermatogenic failure and reduced serum T/LH. WHAT IS KNOWN ALREADY: Primary spermatogenic defects have been associated with functional and morphological abnormalities of LCs, characterized by decreased serum testosterone (T) levels, decreased T/LH, increased 17ß-estradiol (E2) and E2/T ratio, and larger clusters of LCs (LC hyperplasia). CYP17A1 is a key enzyme in the testosterone pathway and has been implicated in the steroidogenic lesion produced by E2 stimulation. STUDY DESIGN, SIZE, DURATION: We studied 18 azoospermic patients with Sertoli cell-only syndrome (SCOS) and signs of LC dysfunction (cases) and 10 obstructive azoospermic/oligozoospermic men with normal spermatogenesis (controls). The SCOS patients were sub-grouped into 9 cases with T/LH <2 and 9 cases with T/LH ≥2. All of the men underwent testicular biopsy for sperm retrieval at the Reproductive Unit of a University Hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS: The transcriptional expression of CYP17A1 and SF-1 (steroidogenic factor 1) was quantified by SYBR®Green-based qPCR in LCs isolated by laser capture microdissection (LCM), and relative expression to the control pool was assessed. CYP17A1 protein expression was semi-quantified by indirect immunofluorescence (IFI) using Image-Pro Plus v7.0 (Media Cybernetics) in testicular tissue. FSH and LH serum concentrations, and serum and intratesticular T (ITT) and E2 (ITE2) were measured by IRMA and RIA, respectively. MAIN RESULTS AND THE ROLE OF CHANCE: Relative CYP17A1 mRNA expression was increased in cases with T/LH <2 compared to cases with T/LH ≥2, by a mean of 3.3-fold (P = 0.002). No corresponding increase in protein expression was found; in fact, CYP17A1 immunostaining intensity assessed by the Integrated Optical Density (IOD) parameter was lower in the cases with T/LH <2 compared to controls (P = 0.008). Relative SF-1 mRNA expression was similar in both case subgroups. CYP17A1 mRNA expression correlated with ITE2 and intratesticular E2/T (r = 0.536; P = 0.026 and r = 0.542; P = 0.016, respectively), while an inverse association was observed for ITE2 and protein level expression (r = -0.421; P = 0.05). LARGE SCALE DATA: Not applicable. LIMITATIONS REASONS FOR CAUTION: We should interpret the results of the semi-quantification of immunofluorescent staining by Image-Pro Plus software with caution, because it is a semi-quantitative method that may have certain difficulties regarding the disposition of protein in the cells. However, it is not influenced by variations in the number of cells that express the protein, as could be the case of western blot analysis in testicular tissue. WIDER IMPLICATIONS OF THE FINDINGS: Dysfunctional LCs of men with SCOS show post-transcriptional deregulation of CYP17A1, with increased mRNA and decreased protein expression, which may be modulated by increased ITE2 levels. In addition, transcriptional expression of CYP17A1 was not associated with changes in SF-1 mRNA expression. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Fund for Scientific and Technological Development (FONDECYT) of Chile to A.C. [grant number 1120176]. The authors declare no conflict of interest.
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Células Intersticiais do Testículo/metabolismo , Síndrome de Células de Sertoli/metabolismo , Esteroide 17-alfa-Hidroxilase/metabolismo , Humanos , Hormônio Luteinizante/metabolismo , Masculino , Fator Esteroidogênico 1/metabolismo , Testosterona/metabolismoRESUMO
STUDY QUESTION: Are copy number variations (CNVs) in the pseudoautosomal regions (PARs) frequent in subjects with Y-chromosome microdeletions and can they lead to abnormal stature and/or neuropsychiatric disorders? SUMMARY ANSWER: Only subjects diagnosed with azoospermia factor (AZF)b+c deletions spanning to the end of the Y chromosome (i.e. terminal deletions) harbor Y isochromosomes and/or cells 45,X that lead to pseudoautosomal gene CNVs, which were associated with abnormal stature and/or neuropsychiatric disorders. WHAT IS KNOWN ALREADY: The microdeletions in the long arm of the Y chromosome (Yq) that include the loss of one to three AZF regions, referred to as Yq microdeletions, constitute the most important known etiological factor for primary spermatogenic failure. Recently, controversy has arisen about whether Yq microdeletions are associated with gain or loss of PAR genes, which are implicated in skeletal development and neuropsychiatric function. STUDY DESIGN, SIZE, DURATION: We studied a cohort of 42 Chilean patients with complete AZF deletions (4 AZFa, 4 AZFb, 23 AZFc, 11 AZFb+c) from a university medical center, diagnosed over a period of 15 years. The subjects underwent complete medical examinations with special attention to their stature and neuropsychiatric function. PARTICIPANTS/MATERIALS, SETTING, METHODS: All subjects were characterized for Yq breakpoints by PCR, and for CNVs in PARs by multiplex ligation-dependent probe amplification (MLPA), followed by qPCR analysis for genes in PAR1 (SHOX and ZBED1), PAR2 (IL9R) and two single copy genes (SRY and DDX3Y, respectively located in Yp11.3 and AZFa). In addition, karyotypes revision and fluorescence in situ hybridization (FISH) for SRY and centromeric probes for X (DXZ1) and Y (DYZ3) chromosomes were performed in males affected with CNVs. MAIN RESULTS AND THE ROLE OF CHANCE: We did not detect CNVs in any of the 35 AZF-deleted men with interstitial deletions (AZFa, AZFb, AZFc or AZFb+c). However, six of the seven patients with terminal AZFb+c deletions showed CNVs: two patients showed a loss and four patients showed a gain of PAR1 genes, with the expected loss of VAMP-7 in PAR2. In these patients, the Yq breakpoints localized to the palindromes P8, P5 or P4. In the four cases with gain of PAR1, qPCR analysis showed duplicated signals for SRY and DDX3Y and one copy of IL9R, indicating isodicentric Yp chromosomes [idic(Y)] with breakpoint in Yq11.22. The two patients who had loss of PAR1, as shown by MLPA, had an additional reduction for SRY and DDX3Y, as shown by qPCR, associated with a high proportion of 45,X cells, as determined by FISH and karyotype. In agreement with the karyotype analysis, we detected DYZ3++ and DYZ3+ cells by FISH in the six patients, confirming idic(Y) and revealing additional monocentric Y chromosome [i(Y)]. Five patients had a history of major depressive disorders or bipolar disorder, and three had language impairment, whereas two patients showed severe short stature (Z score: -2.75 and -2.62), while a man with bipolar disorder was very tall (Z score: +2.56). LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: The number of males studied with Y-chromosome microdeletions and normozoospermic controls with normal karyotypes may not be enough to rule out an association between AZF deletions and PAR abnormalities. The prevalence of Y isochromosomes and/or 45,X cells detected in peripheral blood does not necessarily reflect the variations of PAR genes in target tissues. WIDER IMPLICATIONS OF THE FINDINGS: This study shows that CNVs in PARs were present exclusively in patients with terminal AZFb+c deletions associated with the presence of Y isochromosomes and 45,X cells, and may lead to neuropsychiatric and growth disorders. In contrast, we show that men with interstitial Yq microdeletions with normal karyotypes do not have an increased risk of PAR abnormalities and of phenotypical consequences. Moreover, our results highlight the importance of performing molecular studies, which are not considered in the usual screening for patients with Yq microdeletions. STUDY FUNDING/COMPETING INTERESTS: This work was supported by the National Fund for Scientific and Technological Development of Chile (FONDECYT), grant no. 1120176 (A.C.). The authors declare that no conflicting interests exist.
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Cromossomos Humanos Y , Transtornos do Crescimento/psicologia , Isocromossomos , Transtornos Mentais/genética , Oligospermia/genética , Regiões Pseudoautossômicas/genética , Adolescente , Adulto , Estatura/genética , Deleção Cromossômica , Variações do Número de Cópias de DNA , Humanos , Masculino , Adulto JovemRESUMO
Elevated intratesticular levels of hydroxyoestradiols and methoxyoestradiols, two classes of endogenous oestradiol metabolites, have been associated with male infertility. The aim of this study was to explore the effects of 2-hydroxyoestradiol (2OHE2 ), 4-hydroxyoestradiol (4OHE2 ), 2-methoxyoestradiol (2ME2 ) and 4-methoxyoestradiol (4ME2 ) on Sertoli cell viability. For this, TM4 cells were incubated with different concentrations of these metabolites for 24 h to then evaluate the viability and DNA integrity by MTS and TUNEL assay respectively. The participation of classical oestrogen receptors and the involvement of oxidative stress and apoptotic mechanisms were also evaluated co-incubating TM4 cells with these estradiol metabolites and with the drugs ICI182780, N-acetylcysteine and Z-VAD-FMK respectively. Only high concentrations of 2OHE2 and 2ME2 decreased cell viability inducing DNA fragmentation. In addition, ICI182780 did not block the effect of 2OHE2 and 2ME2 , while N-Acetylcysteine and Z-VAD-FMK only blocked the effect of 2OHE2 . Moreover, 2OHE2 but not 2ME2 induced PARP and caspase-3 cleavage. Finally, lower 2OHE2 and 2ME2 concentrations (0.01-0.1-1.0 µmol l-1 ) decreased Sertoli cell viability 48 h post-treatment. Our results support the hypothesis that elevated intratesticular 2OHE2 or 2ME2 concentrations could be related to male infertility since 2OHE2 by apoptosis and 2ME2 by undetermined mechanisms induce DNA fragmentation in Sertoli cells.
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Fragmentação do DNA/efeitos dos fármacos , Estradiol/análogos & derivados , Células de Sertoli/efeitos dos fármacos , 2-Metoxiestradiol , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Criança , Estradiol/farmacologia , Antagonistas do Receptor de Estrogênio/farmacologia , Fulvestranto , Humanos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Células de Sertoli/metabolismoRESUMO
This work examines the new possibilities introduced with the arrival of commercially available high-resolution continuum source atomic absorption spectrometers for the determination of metalloids (B, Si, Ge, As, Se, Sb and Te) and non-metals (P, S, F, Cl, Br, I and N-based species), such as the improved potential to detect and correct for spectral overlaps and the strategies available to correct for matrix effects. In particular, and considering the increasing number of papers reporting on the use of molecular absorption spectrometry using graphite furnaces and flames as vaporizers, the work discusses in detail the advantages and limitations derived from the monitoring of molecular spectra from a practical point of view, in an attempt to guide future users of the technique.
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The development and optimization of renewable energy systems are some of the most necessary topics to advance towards secure and sustainable energy models. Photovoltaic energy is one of those sustainable options that could contribute to the reduction of greenhouse gas emissions. The optimal angle of solar incidence producing the highest absorption in a day is an important parameter to install photovoltaic systems. This value is often estimated using simulation models based on geographic location; however, those models ignore the influence of nearby obstruction objects, albedo, and local weather conditions. Such a problem is addressed in this work by designing a system to estimate the optimum angle of solar incidence for the photovoltaic panels. The system is based on an arrangement of 33 measurement points spaced in arcs every 45 degrees in azimuth and every 22.5 degrees in elevation, which provides a wide range for analysis. The light captured by each optical fiber is transmitted to a flat array where the power is measured using a single RGB camera.
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Backgrounds. The elevated prevalence and enormous clinical and social impact of fibromyalgia, together with the complexity of its treatment, require action consensuses that guide health care professionals. Although there are some similar documents in our language, most have been made from the perspective of a single discipline.Objective. To develop a consensus on the treatment of fibromyalgia made by selected representatives and supported by the principal medical associations that intervene in its treatment (rheumatology, neurology, psychiatry,rehabilitation and family medicine) and representatives of the associations of patients. On the other hand, understanding the disease not as a homogenous disorders but also as the sum of different clinical subtypes,having specific symptomatic characteristics and different therapeutic needs is stressed. This approach represented a need perceived by the clinicians and a novelty regarding previous consensuses.Methods. The different clinical classifications proposed in fibromyalgia and the scientific evidence of the treatments used in this disease were reviewed. For the selection of the classification used and performance of the therapeutic recommendations, some of the usual techniques to obtain the consensus (nominal group and brainstorming) were used.Conclusion. The classification of Giesecke of fibromyalgia into 3 subgroups seems to have the greatest scientific evidence and the most useful for the clinician. The guide offers a series of general recommendations for all the patients with fibromyalgia. However, in addition, for each subgroup, there are a series of specific pharmacological and psychological-type recommendations and those of modification of the environment, which will make it possible to have a personalized approach to the patient with fibromyalgia in accordance with their individual clinical characteristics (pain, catastrophizing levels, etc.).
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Terapia por Exercício/métodos , Fibromialgia/terapia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Exercício Físico/fisiologia , Fibromialgia/classificação , Fibromialgia/diagnóstico , Fibromialgia/psicologia , Humanos , Educação de Pacientes como Assunto , Participação do Paciente , Qualidade de VidaRESUMO
BACKGROUND AND PURPOSE: Moebius sequence comprises a spectrum of brain congenital malformations predominantly affecting the function of multiple cranial nerves. Reported neuroimaging findings are heterogeneous and based on case reports or small case series. Our goal was to describe the neuroimaging findings of Moebius sequence in a large population of patients scanned with MR imaging. MATERIALS AND METHODS: An observational cross-sectional study was performed to assess brain MR imaging findings in 38 patients with Moebius syndrome studied between 2013 and 2016. RESULTS: Retrospective analysis of MR imaging studies showed flattening of the floor of the fourth ventricle floor secondary to a bilateral absent facial colliculus in 38 patients (100%) and unilateral absence in 1. A hypoplastic pons was found in 23 patients (60.5%). Mesencephalic malformations consisted of tectal beaking in 15 patients (39.5%) and increased anteroposterior midbrain diameter with a shallow interpeduncular cistern in 12 (31.6%). Infratentorial arachnoid cysts were found in 5 patients (13.2%), and cerebellar vermis hypoplasia, in 2 (5.3%). Supratentorial findings included the following: thalamic fusion (26.3%), periventricular nodular heterotopias (26.3%), ventriculomegaly (26.3%), callosal abnormalities (23.7%), and hippocampal malrotations (23.7%). CONCLUSIONS: Findings seen in this large patient cohort agreed with previously published reports. Flattening of the fourth ventricle floor secondary to a bilaterally absent facial colliculus was the most frequent MR imaging finding. The presence of other brain stem and cerebellar malformations as well as supratentorial abnormalities may help explain clinical symptoms and achieve a correct diagnosis.
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Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Síndrome de Möbius/diagnóstico por imagem , Síndrome de Möbius/patologia , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino , Neuroimagem/métodos , Estudos Retrospectivos , Adulto JovemRESUMO
Several observational studies have showed a combination of lower testosterone (T) to LH ratio and higher estradiol (E2 ) to T ratio in secretory infertile men compared to men with normal spermatogenesis, suggesting a steroidogenic dysfunction of Leydig cells (Lc) that may involve increased aromatase activity. Low T/LH ratio is associated with Lc hyperplasia, which together with LH hyperstimulation may represent compensation for impaired T production. Aromatase expression and oestrogen production are mainly detected in Lc of the testis, although Sertoli and germ cells also contribute to testicular aromatase activity. The aim of this study was to assess the transcriptional expression of CYP19A1 (aromatase) in isolated Lc of subjects with Sertoli cell-only syndrome (SCOS) and signs of Lc impairment. Nineteen patients with SCOS and 10 controls with normal spermatogenesis who had medical indication of testicular biopsy for sperm retrieval were studied. Leydig cells were isolated by Laser Capture Microdissection (LCM) and CYP19A1 mRNA expression was quantified by SYBR® Green-based qPCR. In addition, testicular T and E2 and serum hormonal levels were measured. Relative to control group, CYP19A1 was overexpressed more than twofold in 10/19 cases (2.3-12.2-fold increase), showing a significant increment in cases with low T/LH ratio (T/LH < 2) compared to cases with T/LH ≥ 2 (p = 0.038, REST® ). Moreover, Rq data for CYP19A1 had a direct correlation with testicular levels of E2 and the E2 /T ratio (r = 0.869; p < 0.001 and r = 0.633; p = 0.005). In summary, Lc from infertile patients with signs of Lc dysfunction overexpressed aromatase and showed an increment of testicular E2 . Our results suggest that increased expression of aromatase in Lc leads to higher E2 production and may account for the functional impairment of the Lc in patients with SCOS.
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Aromatase/genética , Células Intersticiais do Testículo/metabolismo , Síndrome de Células de Sertoli/genética , Testículo/metabolismo , Adulto , Aromatase/metabolismo , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Microdissecção e Captura a Laser , Hormônio Luteinizante/sangue , Masculino , Síndrome de Células de Sertoli/metabolismo , Espermatogênese/genética , Testosterona/sangueRESUMO
Transmissible venereal tumour (TVT) generally presents different degrees of aggressiveness, which makes them unresponsive to conventional treatment protocols. This implies a progressive alteration of their biological profile. This study aimed to evaluate the cytotoxicity, cell survival, apoptosis and cell cycle alterations in TVT cell cultures subjected to treatment with vincristine. Similarly, it assessed possible implications of MDR-1, TP53, BCL-2, and BAX gene expressions in eight TVT primary cultures for both resistance to chemotherapy and biological behaviour. When comparing TVT cells receiving vincristine to those untreated, a statistical difference related to increased cytotoxicity and decreased survival rates, and alterations in G1 and S cell cycle phases were found but without detectable differences in apoptosis. Increased MDR-1 gene expression was observed after treatment. The groups did not differ statistically in relation to the TP53, BAX and BCL-2 genes. Although preliminary, the findings suggest that such augmented expression is related to tumour malignancy and chemotherapy resistance.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos Fitogênicos/uso terapêutico , Apoptose , Ciclo Celular , Doenças do Cão/patologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Tumores Venéreos Veterinários/patologia , Vincristina/uso terapêutico , Proteína X Associada a bcl-2/metabolismo , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Doenças do Cão/tratamento farmacológico , Cães , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica , Resultado do Tratamento , Tumores Venéreos Veterinários/tratamento farmacológicoRESUMO
Estradiol (E2 ) is normally metabolized to hydroxyestradiols and methoxyestradiols by CYP1A1, CYP1B1 and COMT. However, an altered production of these metabolites by a disturbed expression of these enzymes is associated with reproductive and non-reproductive pathologies. In vitro studies suggest that increased hydroxyestradiols and methoxyestradiols intratesticular generation is related to male infertility, but no studies have explored whether infertile men have a disturbed testicular expression of the enzymes that generate these E2 metabolites. The aim of this study was to assess CYP1A1, CYP1B1 and COMT testicular expression at mRNA and protein level in men with spermatogenic impairment. Seventeen men with primary spermatogenic failure (13 with Sertoli cell-only syndrome and four with maturation arrest) and nine controls with normal spermatogenesis were subjected to testicular biopsy. mRNA was quantified using real-time RT-PCR and protein expression was evaluated using western blot and immunohistochemistry followed by integrated optic density analysis. Besides, the effects of hydroxyestradiols and methoxyestradiols on testosterone-induced transcriptional activity were evaluated in TM4 cells using a luciferase reporter assay system. Our results show that patients with Sertoli cell-only syndrome had significantly elevated COMT expression at the mRNA level, higher COMT immunoreactivity in their seminiferous tubules and increased protein expression of the soluble COMT isoform (S-COMT), whereas patients with maturation arrest had significantly elevated CYP1A1 mRNA levels and higher CYP1A1 immunoreactivity in interstitial space. Finally, 2-hydroxyestradiol decreased testosterone-induced transcriptional activity in Sertoli cells in vitro. In conclusion, male infertility is related to disturbed testicular expression of the enzymes responsible for producing hydroxyestradiols and/or methoxyestradiols. If these changes are related with increased intratesticular hydroxyestradiols and methoxyestradiols concentrations, they could elicit an impaired Sertoli cell function. Our results suggest CYP1A1 and COMT as new potential targets in treating male infertility.
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Catecol O-Metiltransferase/biossíntese , Citocromo P-450 CYP1A1/biossíntese , Infertilidade Masculina/metabolismo , Células de Sertoli/patologia , Adulto , Animais , Western Blotting , Linhagem Celular , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Reação em Cadeia da Polimerase em Tempo Real , Células de Sertoli/metabolismoRESUMO
This paper reports a theoretical investigation of the structure, stability, and electron charge density of cubic, rhombohedral, hexagonal, and monoclinic Al lattices. The equations of state and the elastic constants are computed from total energy calculations at different volumes and unit cell strains using the density functional theory approximation. The topology of the electron density is analyzed within the crystalline implementation of the atoms in molecules formalism. The results are discussed in light of the so-called anions in metallic matrices model, which permits the interpretation of the chemical bonding and the explanation of the existence of particular symmetries of inorganic crystals. First, the Al sublattices are identified as the reference building blocks of AlX(3) (X = F, Cl, OH) compounds. The calculations reveal that the equilibrium zero-pressure Al-Al shortest distance is around 2.75 A in all of the Al matrixes, similar to the value observed in the stable face centered cubic structure of Al at room conditions. Second, at their zero-pressure equilibrium geometries, the Al sublattices are found to fulfill the mechanical stability criteria or, alternatively, to show mechanical instabilities that are compatible with the distortions observed for the structures in AlX(3) crystals. However, at the equilibrium volumes of the AlX(3) crystals, all of the Al matrices violate the spinodal condition, and the cohesion and stabilization are provided by the nonmetallic X atoms. Third, the structural anisotropy of the Al sublattices seems to be the main factor to discriminate metallic matrices able to host nonmetallic elements. The inhomogeneities of the electron charge density, which favor the arrival of nonmetallic elements and the crystal formation, are notably enhanced in passing from the fcc structure of pure Al to the less isotropic Al matrices observed in AlX(3) compounds.
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Molecular systematic analysis of the annexin gene superfamily characterized the evolutionary origin, frequency and range of structural variation in calcium interaction domains that are considered intrinsic for membrane targeting and ion channel function. Approximately 36% of annexin repeat domains in an estimated 100 distinct subfamilies contained amino acid changes consistent with the functional loss of type two calcium-binding sites. At least 11% of annexin domains contained a novel K/H/RGD motif conserved in particular subfamilies and manifest in all phyla, apparently via convergent evolution. The first yeast annexin from Yarrowia lipolytica was classified in the ANXC1 subfamily with fungal and mycetozoan representatives. This clade had intact calcium-binding sites but disruption of the normally well-conserved, mid-repeat 4 region implicated in calcium channel regulation. Conversely, a tandem pair of novel annexins from the amphioxus Branchiostoma floridae resembled annexin A13 in gene structure and conserved the charged amino acids associated with the internal hydrophilic pore, but were devoid of external type 2 calcium-binding sites and incorporated K/RGD motifs instead, like annexin A9. The selective erosion of calcium-binding sites in annexin domains and the occurrence of alternate ligands in the same exposed, interhelical loops are pervasive features of the superfamily. This suggests greater complexity than previously appreciated in the mechanisms controlling annexin membrane interaction and calcium channel operation.
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Anexinas/metabolismo , Cálcio/metabolismo , Sequência de Aminoácidos , Animais , Anexinas/química , Anexinas/classificação , Sítios de Ligação , Humanos , Dados de Sequência Molecular , FilogeniaRESUMO
Complex interactions between androgen and estrogen (E2) regulate prostatic development and physiology. We analyzed the early effects of a high single dose of E2 (25 mg/kg body weight) and castration (separately or combined) on the adult 90-day-old male Wistar rat ventral prostate. Androgen levels, prostate weight, and the variation in the relative and absolute volume of tissue compartments and apoptotic indices were determined for 7 days. Castration and exogenous E2 markedly reduced ventral prostate weight (about 50% of the control), with a significant reduction in the epithelial compartment and increased stroma. The final volume of the epithelium was identical at day 7 for all treatments (58.5% of the control). However, E2 had an immediate effect, causing a reduction in epithelial volume as early as day 1. An increase in smooth muscle cell volume resulted from the concentration of these cells around the regressing epithelium. The treatments resulted in differential kinetics in epithelial cell apoptosis. Castration led to a peak in apoptosis at day 3, with 5% of the epithelial cells presenting signs of apoptosis, whereas E2 caused an immediate increase (observed on day 1) and a sustained (up to day 7) effect. E2 administration to castrated rats significantly increased the level of apoptosis by day 3, reaching 9% of the epithelial cells. The divergent kinetics between treatments resulted in the same levels of epithelial regression after 7 days (approximately 30% of control). These results show that E2 has an immediate and possibly direct effect on the prostate, and anticipates epithelial cell death before reducing testosterone to levels as low as those of castrated rats. In addition, E2 and androgen deprivation apparently cause epithelial cell death by distinct and independent pathways.
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Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Estradiol/farmacologia , Próstata/efeitos dos fármacos , Animais , Imuno-Histoquímica , Masculino , Orquiectomia , Próstata/citologia , Próstata/crescimento & desenvolvimento , Ratos , Ratos Wistar , Testosterona/sangue , Fatores de TempoRESUMO
RESUMEN Objetivo. El objetivo de este estudio fue describir las medidas corporales e índices zoométricos de Ovinos de Pelo Criollos Colombianos (OPC), en dos de sus variedades, Sudán Bayo y Sudán Blanco. Materiales y métodos. Esta investigación fue llevada a cabo en los departamentos de Córdoba, Cesar y La Guajira, se visitaron dos granjas en cada uno de los primeros dos departamentos y una en el tercero. 21, 75 y 14 animales por departamento fueron evaluados, respectivamente. Se estudiaron 29 variables morfoestructurales y el peso corporal en 110 ovejas Sudán, y con estas variables evaluadas, se construyeron 15 índices zoométricos. A la información recolectada se le aplicó estadística descriptiva mediante el software InfoStat®. Resultados. Las Sudán Bayo presentaron valores superiores a las Sudán Blanco para el peso (40.8 y 40.57 kg), al igual que para todas las medidas zoométricas relativas a la cabeza, las extremidades y la mayoría de las del tronco; para la primera variedad se emplearon 83 ejemplares y para la segunda 27. En cuanto a los índices zoométricos, las Sudán se caracterizaron por ser dolicocraniotas, dolicocéfalas, eumétricas, de tórax con tendencia elíptica, de grupas convexilíneas y de acuerdo a dos índices etnológicos longilíneas, mientras que con base en un índice funcional brevilíneas. Conclusiones. A través de esta investigación se conoció de manera detallada el estado morfométrico actual de las OPC Sudán, así como también la proporcionalidad entre las regiones corporales de estas, cuya inclinación es hacia el biotipo cárnico. Esta información es de importancia para el conocimiento, caracterización racial, definición de biotipo, conservación, fomento y mejora genética de los OPC.
ABSTRACT Objective. The objective of this study was to describe the body measurements and zoometric indices of Sudán Bayo and Sudán Blanco, two breed varieties of Colombian creole woolless sheep (OPC). Materials and methods. This research was carried out in the departments of Córdoba, Cesar, and La Guajira. Two farms were visited in each of the first two departments and one farm in the third department. Twenty-one, 75, and 14 animals were evaluated in each department, respectively. Twenty-nine morphostructural variables and body weight were studied in 110 Sudán sheep. Based on this, 15 zoometric indices were also estimated. Descriptive statistic was applied to the information collected through the InfoStat® software. Results. Sudán Bayo sheep had higher values than Sudán Blanco sheep for the body weight (40.8 and 40.57 kg), as well as for all the zoometric measurements relative to the head and extremities, and most of the trunk morphometric measurements; in the first breed variety 83 ewes were used and in the second 27 individuals. Regarding the zoometric indices, Sudán sheep were characterized as dolichocranial, dolichocephalic, eumetric, of thorax with elliptical tendency, convex rump, and longilineal animals according to two ethnological indices while brevilineal animals based on one functional index. Conclusions. Through this investigation, the current morphometric status of Sudán OPC sheep was known in detail, as well as the proportionality between the corporal regions of these, whose inclination is towards the meat biotype. This information is of importance for the breed recognition and characterization, biotype definition, conservation, development, and genetic improvement of OPC sheep.
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RESUMEN Objetivo. Esta investigación tuvo como objetivo describir la morfología cualitativa y faneróptica de hembras Ovino de Pelo Criollo Colombiano (OPC) Sudán. Materiales y métodos. Se evaluaron seis características fanerópticas y siete morfológicas cualitativas en 115 hembras Sudán Bayo y Sudán Blanco, de los departamentos Córdoba, Cesar y La Guajira. Los datos obtenidos se analizaron a través del programa estadístico InfoStat® y se estimaron las frecuencias relativas y absolutas para cada uno de los caracteres evaluados. Resultados. Los OPC Sudán Bayo se distinguieron por ser de un color de capa bayo amarillo. Los Sudán Blanco fueron de capa overo castaño, pero predominando siempre el blanco sobre el castaño. Estos ovinos se caracterizaron por poseer mucosas negra-rosadas y en menor proporción habían individuos con mucosas rosadas. Además, presentaron orejas horizontales siempre, perfiles subconvexos en más del 80% de los casos, cuellos generalmente medianos y poco musculados, grupas usualmente inclinadas, ubres parcialmente pigmentadas y también despigmentadas. Asimismo, se caracterizaron por ostentar pezuñas veteadas mayoritariamente, aunque con un alto porcentaje de pezuñas claras en las Sudán Blanco. Conclusiones. Este trabajo ha permitido caracterizar de manera específica a las OPC Sudán desde la morfología y la faneróptica, obteniéndose así información de importancia para delimitar los parámetros de pertenencia a este grupo y para la propuesta de creación de un estándar racial.
ABSTRACT Objective. The objective of this research was to describe the qualitative morphology and phaneroptic of Sudán Colombian creole woolless sheep (OPC). Materials and methods. Six phaneroptic and seven qualitative morphological characteristics were evaluated in a total of 115 Sudán Bayo and Sudán Blanco ewes, from the departments Córdoba, Cesar and La Guajira. The data obtained were analyzed through the statistical program InfoStat®, relative and absolute frequencies were estimated for each evaluated trait. Results. Sudán Bayo OPC were distinguished by being yellow coat color. Sudán Blanco were white-and-chestnut spotted coat color, but white always predominated over chestnut. These ovines usually had black-rosy mucosae and in lesser amount there were individuals with rosy mucosae. Besides, they presented horizontal ears always, sub-convex profile in more than 80% of cases, generally medium-sized and scant muscled necks, usually inclined rumps, partially pigmented and depigmented udders as well. Likewise, they were characterized by showing marbled hooves mostly, but with a high percentage of clear hooves in Sudán Blanco sheep. Conclusions. This research has allowed to characterize specifically. Sudán OPC sheep from morphology and phaneroptic; thus, important information has been obtained to delimit the parameters of belonging to this group and for proposing the creation of a breed standard.
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Animais , OvinosRESUMO
OBJECTIVE: To analyze the radiodensity of commonly used medications and determine their ability to be seen on plan x-ray films. MATERIAL AND METHODS: Under conditions intended to simulate a patient undergoing radiography of the abdomen (including the use of a patient-equivalent phantom), 50 prescription and nonprescription drugs were tested. Their radiodensities were quantified, and their visibility on plain x-ray films was noted. The study drugs were then ranked in order of decreasing radiodensity. In addition, we report an illustrative case of ingested pills in the stomach that mimicked gallstones, a phenomenon we termed "pseudogallstones". RESULTS: In a 71-year-old woman with upper abdominal pain and nausea, a presumptive diagnosis of gallstones based on x-ray findings was subsequently found to be retained iron tablets. This case prompted our assessment of the radiodensity of medications frequently prescribed for elderly patients. Although all 50 medications studied were visible on plain x-ray films, a 13-fold difference was found in their relative radiodensities. Of the medications studied, potassium chloride was the most radiodense, and prednisone was the least radiodense. As a group, minerals were the most radiodense of all medications studied. CONCLUSION: Numerous commonly prescribed medications in their undissolved, undigested state are visible on plain x-ray films, as are mineral supplements, which have high radiodensities. At times, the appearance of these medications and supplements may be confused with organic pathologic conditions.
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Sistema Digestório/diagnóstico por imagem , Migração de Corpo Estranho/diagnóstico por imagem , Preparações Farmacêuticas , Comprimidos , Idoso , Neoplasias da Mama/diagnóstico por imagem , Colelitíase/diagnóstico por imagem , Erros de Diagnóstico , Feminino , Humanos , Ferro/administração & dosagem , Imagens de Fantasmas , Radiografia , Estômago/diagnóstico por imagemRESUMO
INTRODUCTION: Abdominal wall closure is not possible in large congenital defects, even after extensively stretching in to enlarge its capacity. The skin coverage is usually adequate but the aponeurotic defect has to be closed temporally using synthetic patches. The use of these materials leads to increase complication such as infection, fistula formation and extrusion. In addition a second operation is required to remove the material and to perform a definitive closure. The role of fascia lata in reconstruction of abdominal wall is well established as free grafts, pedicled flaps or free flaps. Bank cadaveric fascia lata is used extensively in neurosurgical, ophtalmological, orthopaedic and urogynecological procedures. This is the first description of the use of cadaveric fascia lata for the closure of large abdominal wall defects. CASE REPORTS: We present two cases of congenital diaphragmatic hernia. The first patient was a newborn who presented the impossibility to close the fascia, that was salvaged by a teflón patch. Five months later the wound opened, leaving the mesh exposed that had to be removed. A cadaveric fascia lata patch was used to cover the defect, closing the skin satisfactorily. The second case was a two days newborn. We performed the diaphragmatic closure, and the aponeurotic defect was closed using cadaveric fascia lata. RESULTS: Cosmetic and functional appearance are satisfactory in both cases and no complications have been seen. CONCLUSION: Fascia lata patches are revascularized in the abdominal wall and incorporates into receptor tissue. They have the following advantages with respect to synthetic materials: First, the risk of complications is lower. Second, their removal is not necessary. Finally, no intraperitoneal adhesions occur. The risks of disease transmission and rejection are minimized by the Centro Comunitario de Transfusiones donor selection and processing of the cadaveric fascia lata.
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Músculos Abdominais/cirurgia , Fascia Lata/transplante , Cadáver , Humanos , Recém-Nascido , MasculinoRESUMO
RESUMO O Tumor Venéreo Transmissível Canino (TVTC) é uma neoplasia de células redondas que tem a particularidade de se implantar em mucosas que tenham perdido a sua integridade. Nesse local o tumor prolifera e ocasionalmente origina metástase. Em geral, o tumor responde ao tratamento com sulfato de vincristina, porém a resistência quimioterápica associada ao fenótipo tumoral tem sido documentada. Objetivou-se relatar um caso de TVTC genital de fenótipo citológico misto com metástase esplênica e o insucesso da quimioterapia com sulfato de vincristina, em uma fêmea canina, da raça Australian Cattle Dog, de cinco anos de idade. Após diagnóstico citológico e histológico, o tumor primário foi ainda caracterizado em fase de progressão e mostrou baixa expressão de moléculas do complexo principal de histocompatibilidade (MHC) (4,4 ± 2% classe I e 11 ± 4,1% classe II). A cadela foi submetida à ovariohisterectomia e esplenectomia terapêutica e não apresentou recidiva do tumor após 12 meses de acompanhamento clínico.
ABSTRACT The canine transmissible venereal tumor is a type of round cell cancer that have the particularity of implanting in mucous tissue, when they lose their integrity, at which point the tumour proliferates and may even develop metastases. The tumor typically responds well to vincristine sulfate chemotherapy, although there are cases of resistance to the drug correlated with the tumoral phenotype. We describe herein a genital mixed TVTC case with metastases at spleen and failure at vincristine sulfate chemotherapeutic treatment in a five years old Australian Cattle Dog female. After the cytological, histological and cytogenetic diagnostic, the primary tumor was still characterized in progression phase and showed low major histocompatibility complex expression MHC (4,4 ± 2% class I e 11 ± 4,1% class II. The dog underwent therapeutic splenectomy and ovariohysterectomy and did not present tumor recurrence within 12 months of clinical follow-up.
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Animais , Tumores Venéreos Veterinários , Vincristina , Cães , Genitália , Histerectomia , Mucosa , Metástase Neoplásica , Neoplasias , Recidiva , Esplenectomia , Sulfatos , Terapêutica , Tecidos , Preparações Farmacêuticas , Tratamento Farmacológico , HistocompatibilidadeRESUMO
A potential drawback of traditional dietary metal toxicity studies is that it is difficult to distinguish between the direct toxicity of the metal and indirect effects caused by altered concentrations of essential nutrients in the metal-contaminated diet. In previous studies it has become clear that this can hamper the study of the real impact of dietary metal exposure and also complicates the analysis of the mechanisms of dietary metal toxicity in filter-feeding freshwater invertebrates like Daphnia magna. This problem has been partly circumvented by the production of liposomes, since these vectors are invulnerable to metal-induced food quality shifts and as such can be applied to study the mechanisms of dietary metal toxicity without the confounding effect of nutritional quality shifts. The aim of current study was to evaluate if there is relevance for dietary Ni toxicity under natural exposures, i.e., when D. magna is exposed to dietary Ni via living algae, and secondly, to quantify how nutritional quality shifts contribute to the toxic effects that are observed when algae are used as contaminated food vectors. For this aim, liposomes were prepared by the hydration of phosphatidylcholine in media containing 0 (control), 10, 50, 100 and 500 mg Ni/L. The liposome particles were then mixed with uncontaminated green algae in a 1/10 ratio (on a dry wt basis) to make up diets with constant nutrient quality and varying Ni contents (i.e., 1.2 µg Ni/g dry wt in the control and 18.7, 140.3, 165.0 and 501.6 µg Ni/g dry wt in the Ni-contaminated diet, respectively). A second food type was prepared on the basis of a 1/10 mixture (on a dry weight basis) of control liposomes and Ni-contaminated algae, representing a diet that differed in Ni content (i.e., 1.2, 26.8, 84.7, 262.3 and 742.7 µg Ni/g dry wt) and concentrations of essential nutrients (in terms of P and omega 3 poly-unsaturated fatty acids like eicosapentaenoic acid and α-linolenic acid). Both diets were then simultaneously fed to D. magna during a 21-day chronic bioassay, using reproduction, growth, survival, ingestion rate and Ni bioaccumulation as endpoints. Ni delivered by liposomes caused a significant inhibition of reproduction and growth when the metal accumulated to minimum levels of 11.9 and 20.0 µg Ni/g dry wt after 7 and 14 days, respectively. Using algae as Ni vector, similar effects of dietary Ni exposure occurred when algae had been pre-exposed to concentrations of at least 133 µg/L of bioavailable Ni (i.e., Ni2+), which is similar to the reproductive EC50 of waterborne Ni exposure for D. magna (115 µg Ni2+/L). While this may have some consequences for predicting chronic Ni toxicity in this range of Ni concentrations with the biotic ligand model--which could be further improved by including the dietary toxicity pathway in this model, the occurrence of such high concentrations in the field is very rare. Hence, there seems to be very little environmental relevance for dietary Ni toxicity to D. magna. Finally, besides the direct effects of Ni there was no evidence that nutritional quality shifts could have affected daphnids' growth, but it is very likely that the impairment of reproduction at toxic exposure levels of Ni was also partly the result of reduced fatty acid levels.