RESUMO
Male infertility or subfertility is frequently associated with disruption of the hypothalamic-pituitary-testis axis events, like secondary hypogonadism. However, little is known how this condition affects the proteomic composition of the epididymal fluid. In the present study, we evaluated the proteomic changes in the cauda epididymal fluid (CEF) in a swine model of secondary hypogonadism induced by anti-GnRH immunization using multidimensional protein identification technology. Seven hundred and eighteen proteins were identified in both GnRH-immunized and control groups. GnRH immunization doubled the number of proteins in the CEF, with 417 proteins being found exclusively in samples from GnRH-immunized boars. CEF from GnRH-immunized boars presented an increase in the number of proteins related to cellular and metabolic processes, with affinity to organic cyclic compounds, small molecules, and heterocyclic compounds, as well changed the enzymatic profile of the CEF. Also, a significant increase in the number of proteins associated to the ubiquitin-proteasome system was identified in CEF from GnRH-immunized animals. These results bring strong evidence of the impact of secondary hypogonadism on the epididymal environment, which is responsible for sperm maturation and storage prior ejaculation. Finally, the differently expressed proteins in the CEF are putative seminal biomarkers for testicular and epididymal disorders caused by secondary hypogonadism.
Assuntos
Líquidos Corporais/metabolismo , Epididimo/metabolismo , Hipogonadismo/metabolismo , Infertilidade Masculina/metabolismo , Proteoma/metabolismo , Animais , Anticorpos/farmacologia , Líquidos Corporais/química , Líquidos Corporais/efeitos dos fármacos , Anticoncepção Imunológica/métodos , Anticoncepção Imunológica/veterinária , Epididimo/química , Epididimo/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/imunologia , Hormônio Liberador de Gonadotropina/metabolismo , Hipogonadismo/etiologia , Hipogonadismo/imunologia , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Infertilidade Masculina/etiologia , Infertilidade Masculina/imunologia , Infertilidade Masculina/veterinária , Masculino , Modelos Animais , Proteoma/análise , Proteoma/efeitos dos fármacos , Proteômica , Transdução de Sinais/efeitos dos fármacos , Suínos/metabolismo , Testículo/efeitos dos fármacos , Testículo/metabolismoRESUMO
Levonorgestrel (LNG), a synthetic 19 nor-testosterone derivative, is widely used for emergency contraception. It is well known that LNG prevents ovulation only when given prior to the surge of serum luteinizing hormone (LH) during the periovulatory phase of the menstrual cycle. This observation suggests that LNG, given its contraceptive efficacy, has additional effects other than those affecting ovulation. In this study, we have evaluated the effects on human sperm functionality of uterine flushings (UF) obtained from women at day LH + 1 of a control cycle (CTR-LH + 1) and after receiving LNG (LNG-LH + 1) two days before the surge of LH. Human sperm from normozoospermic donors were incubated with UF and protein tyrosine phosphorylation, sperm motility, acrosome reaction as well as zona pellucida (ZP) binding capacity were assessed. A significant decrease in total motility and tyrosine phosphorylation accompanied by an increase on spontaneous acrosome reaction was observed when sperm were incubated in the presence of LNG-LH + 1. None of these effects were mimicked by purified glycodelin A (GdA). Moreover, the addition of UF obtained during the periovulatory phase from LNG-treated women or the presence of purified GdA significantly decreased sperm-ZP binding. The data were compatible with changes affecting sperm capacitation, motility and interaction with the ZP. These results may offer evidence on additional mechanisms of action of LNG as an emergency contraceptive.
Assuntos
Líquidos Corporais , Anticoncepcionais Femininos/uso terapêutico , Levanogestrel/uso terapêutico , Espermatozoides/efeitos dos fármacos , Irrigação Terapêutica , Útero/patologia , Reação Acrossômica/efeitos dos fármacos , Adulto , Líquidos Corporais/efeitos dos fármacos , Líquidos Corporais/fisiologia , Anticoncepcionais Femininos/farmacologia , Feminino , Humanos , Técnicas In Vitro , Levanogestrel/farmacologia , Masculino , Capacitação Espermática/efeitos dos fármacos , Espermatozoides/fisiologiaRESUMO
BACKGROUND: Diarrhea in piglets is one of the main causes of animal death after weaning; zinc oxide (ZnO) has been used in high doses for the control of this sickness. The aim of this study was to determine the physicochemical properties of ZnO nanoparticles synthesized and immobilized on a chitosan/alginate (CH/SA) complex and investigate the antimicrobial activity and in vitro release profile of zinc (Zn2+) from these new compounds. The ZnO nanoparticles composites were prepared and combined with CH/SA or CH/SA and sodium tripolyphosphate (TPP). The structure and morphology of the composites were analyzed by characterization methods such as X-ray diffraction, FTIR spectroscopy, thermogravimetric analysis, atomic absorption spectrophotometry and scanning electron microscopy. RESULTS: The crystallite size of ZnO nano was 17 nm and the novel ZnO composites were effective in protecting ZnO in simulated gastric fluid, where Zn2+ reached a concentration six-fold higher than the levels obtained with the unprotected commercial-zinc oxide. In addition, the novel composites suggest effective antimicrobial activity against Escherichia coli and Staphylococcus aureus. CONCLUSIONS: The results described herein suggest that the novel nano composites may work as an alternative product for pig feeding as verified by the in vitro assays, and may also contribute to lower the zinc released in the environment by fecal excretion in animals waste.
Assuntos
Antibacterianos/farmacologia , Suco Gástrico/efeitos dos fármacos , Nanopartículas , Óxido de Zinco/farmacologia , Alginatos/química , Animais , Antibacterianos/administração & dosagem , Líquidos Corporais/efeitos dos fármacos , Quitosana/química , Escherichia coli/efeitos dos fármacos , Ácido Glucurônico/química , Ácidos Hexurônicos/química , Secreções Intestinais/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Nanopartículas/química , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Suínos , Difração de Raios X , Óxido de Zinco/administração & dosagemRESUMO
Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.
Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Líquidos Corporais/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Núcleos Parabraquiais/efeitos dos fármacos , Agonistas de Receptores Adrenérgicos alfa 2/administração & dosagem , Animais , Líquidos Corporais/fisiologia , Captopril/administração & dosagem , Captopril/farmacologia , Ingestão de Líquidos/efeitos dos fármacos , Furosemida/administração & dosagem , Furosemida/farmacologia , Homeostase/fisiologia , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Núcleos Parabraquiais/fisiologia , Ratos , Cloreto de Sódio na DietaRESUMO
Central α2-adrenoceptors and the pontine lateral parabrachial nucleus (LPBN) are involved in the control of sodium and water intake. Bilateral injections of moxonidine (α2-adrenergic/imidazoline receptor agonist) or noradrenaline into the LPBN strongly increases 0.3 M NaCl intake induced by a combined treatment of furosemide plus captopril. Injection of moxonidine into the LPBN also increases hypertonic NaCl and water intake and reduces oxytocin secretion, urinary sodium, and water excreted by cell-dehydrated rats, causing a positive sodium and water balance, which suggests that moxonidine injected into the LPBN deactivates mechanisms that restrain body fluid volume expansion. Pretreatment with specific α2-adrenoceptor antagonists injected into the LPBN abolishes the behavioral and renal effects of moxonidine or noradrenaline injected into the same area, suggesting that these effects depend on activation of LPBN α2-adrenoceptors. In fluid-depleted rats, the palatability of sodium is reduced by ingestion of hypertonic NaCl, limiting intake. However, in rats treated with moxonidine injected into the LPBN, the NaCl palatability remains high, even after ingestion of significant amounts of 0.3 M NaCl. The changes in behavioral and renal responses produced by activation of α2-adrenoceptors in the LPBN are probably a consequence of reduction of oxytocin secretion and blockade of inhibitory signals that affect sodium palatability. In this review, a model is proposed to show how activation of α2-adrenoceptors in the LPBN may affect palatability and, consequently, ingestion of sodium as well as renal sodium excretion.
Assuntos
Animais , Ratos , /farmacologia , Líquidos Corporais/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Núcleos Parabraquiais/efeitos dos fármacos , /administração & dosagem , Líquidos Corporais/fisiologia , Captopril/administração & dosagem , Captopril/farmacologia , Ingestão de Líquidos/efeitos dos fármacos , Furosemida/administração & dosagem , Furosemida/farmacologia , Homeostase/fisiologia , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Núcleos Parabraquiais/fisiologia , Cloreto de Sódio na DietaRESUMO
The aim of this work was the preparation of inorganic mesoporous materials from silica, calcium phosphate and a nonionic surfactant and to evaluate the incorporation and release of different concentrations of osteogenic growth peptide (OGP) for application in bone regeneration. The adsorption and release of the labeled peptide with 5,6-carboxyfluorescein (OGP-CF) from the mesoporous matrix was monitored by fluorescence spectroscopy. The specific surface area was 880 and 484 m(2) g(-1) for pure silica (SiO) and silica/apatite (SiCaP), respectively; the area influenced the percentage of incorporation of the peptide. The release of OGP-CF from the materials in simulated body fluid (SBF) was dependent on the composition of the particles, the amount of incorporated peptide and the degradation of the material. The release of 50% of the peptide content occurred at around 4 and 30 h for SiCaP and SiO, respectively. In conclusion, the materials based on SiO and SiCaP showed in vitro bioactivity and degradation; thus, these materials should be considered as alternative biomaterials for bone regeneration.
Assuntos
Apatitas/química , Portadores de Fármacos/química , Histonas/farmacologia , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Nanoestruturas/química , Dióxido de Silício/química , Adsorção , Líquidos Corporais/efeitos dos fármacos , Fluoresceínas/química , Humanos , Cinética , Microscopia Eletrônica de Transmissão , Nitrogênio , Porosidade , Espalhamento a Baixo Ângulo , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios XRESUMO
OBJECTIVE: The therapeutic management of parapneumonic pleural effusions (PPE) is controversial in children. Decision-making often relies on parameters such as gross appearance of pleural fluid and on bacteriologic and biochemical analyses. Our goal was to describe the laboratory profile of PPE in children and to assess the influence of previous administration of antibacterial agents on culture and biochemical results. PATIENTS AND METHODS: This was a prospective study including children (age, 1 month to 16 years) with a diagnosis of PPE. Two groups were evaluated: children with or without antibiotic treatment up to 48 hours before analysis of pleural fluid. Results were analyzed using the χ(2) or Mann-Whitney test (α = .05). Odds ratio and 95% confidence intervals (95% CIs) were calculated, with control of previous antibiotic therapy using multivariate logistic regression analysis, to determine the risk of empyema associated with specific biochemical parameters. RESULTS: One hundred ten children were selected. Fifty percent had received antibiotics at least 48 hours before pleural fluid analysis. Differences were observed between the groups in terms of PPE gross appearance (P = .033) and identification of bacteriologic agent by culture or Gram stain (P = .023). Biochemical parameters (pH ≤7.1 and glucose ≤40 mg/dL) were associated with increased odds of receiving a more invasive treatment. For pH, the odds ratio was 9.614 (95% CI, 1.952-47.362; P = .005); and for glucose, 9.201 (95% CI, 1.333-63.496; P = .024). CONCLUSIONS: Previous use of antibacterial agents affected the bacteriologic analysis of pleural fluid in this pediatric sample admitted for PPE. However, it did not interfere significantly with biochemical parameters of pleural fluid.
Assuntos
Antibacterianos/uso terapêutico , Líquidos Corporais/efeitos dos fármacos , Derrame Pleural/metabolismo , Pneumonia Bacteriana/tratamento farmacológico , Adolescente , Técnicas Bacteriológicas , Líquidos Corporais/química , Líquidos Corporais/microbiologia , Criança , Pré-Escolar , Feminino , Glucose/análise , Humanos , Concentração de Íons de Hidrogênio , Lactente , Recém-Nascido , Masculino , Derrame Pleural/microbiologia , Pneumonia Bacteriana/metabolismo , Pneumonia Bacteriana/microbiologia , Estudos ProspectivosRESUMO
Synthetic hydroxyapatite is widely used in medicine and dentistry due its notable biocompatibility and bioactivity properties. The hydroxyapatite incorporation into silica has demonstrated excellent bioactivity or biodegradability, according to the content of calcium ions. Procedures to obtain ordered mesoporous silicates rely on the micelle-forming properties of a surfactant, whose chemical composition, size and concentration control the structural dimensions of the final material. This paper reports the synthesis of two types mesoporous materials: pure MCM-41 and a nanocomposite of apatite and mesoporous silica, MCM-41-HA. The samples were charged with atenolol as a model drug and in vitro release essays were carried out. The bioactivity behavior was investigated as a function of soaking time in simulated body fluid. The materials were characterized by X-ray diffraction, N2 adsorption, FTIR spectroscopy, scanning electron microscopy, dispersive energies spectroscopy, and transmission electron microscopy. The influence of the release rate of atenolol molecules from pure MCM-41 mesoporous and containing hydroxyapatite was demonstrated, since it results in a very slowly drug delivery from the nanocomposite system.
Assuntos
Apatitas/síntese química , Sistemas de Liberação de Medicamentos , Nanocompostos/química , Dióxido de Silício/síntese química , Adsorção/efeitos dos fármacos , Atenolol/farmacologia , Líquidos Corporais/efeitos dos fármacos , Cinética , Microscopia Eletrônica de Transmissão , Nitrogênio/química , Porosidade/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier , Síncrotrons , Difração de Raios XRESUMO
We have studied the effects of L-NG-nitro arginine methyl esther (L-NAME), L-arginine (LAR), inhibitor and a donating nitric oxide agent on the alterations of salivary flow, water intake, arterial blood pressure (MAP) and heart rate (HR) induced by the injection pilocarpine into the subfornical organ (SFO). Rats (Holtzman 250-300 g) were anesthetized with 2, 2, 2-tribromoethanol (20 mg/100 kg b. wt.) and a stainless steel cannula were implanted into their SFO. The volume of injection was 0.2 microl. The amount of saliva secretion was studied over a 5-min period. Pilocarpine (40 microg), L-NAME (40 microg) and LAR (30 microg) were used in all experiments for the injection into the SFO. Pilocarpine (10, 20, 40, 80 and 160 microg) injected into SFO elicited a concentration-dependent increase in salivary secretion. L-NAME injected prior to pilocarpine into the SFO increased salivary secretion and water intake due to the effect of pilocarpine. LAR injected prior to pilocarpine into the SFO attenuated the salivary secretion and water intake. Pilocarpine, injected into the SFO increased the MAP and decreased heart rate (HR). L-NAME injected prior to pilocarpine into the SFO potentiated the pressor effect of pilocarpine with a decrease in HR. LAR injected into the SFO prior to pilocarpine attenuated the increase in MAP with no changes in HR. The present study suggests that the SFO nitrergic cells interfere in the cholinergic pathways implicated in the control of salivary secretion, fluid and cardiovascular homeostasis.
Assuntos
Homeostase/efeitos dos fármacos , Pilocarpina/farmacologia , Órgão Subfornical/efeitos dos fármacos , Animais , Arginina/administração & dosagem , Arginina/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Líquidos Corporais/efeitos dos fármacos , Líquidos Corporais/fisiologia , Fenômenos Fisiológicos Cardiovasculares/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Agonistas Muscarínicos/farmacologia , NG-Nitroarginina Metil Éster/administração & dosagem , NG-Nitroarginina Metil Éster/farmacologia , Doadores de Óxido Nítrico/administração & dosagem , Doadores de Óxido Nítrico/farmacologia , Pilocarpina/administração & dosagem , Ratos , Saliva/efeitos dos fármacos , Salivação/efeitos dos fármacos , Órgão Subfornical/fisiologiaRESUMO
PURPOSE: Positive effects on premenstrual symptoms have been observed with low-dose oral contraceptives. Drospirenone is a synthetic progestogen with antiandrogenic and antimineralocorticoid effects. This open-label, multicenter study evaluated the effects of a combination of ethinylestradiol 30 microg and drospirenone 3 mg on safety, cycle control, general well-being and fluid-related symptoms in women with premenstrual disorders requesting contraception. MATERIALS AND METHODS: A total of 241 healthy volunteers with symptoms of premenstrual disorder was enrolled in the study. Of the final sample, 203 completed the six-cycle treatment and were included in the efficacy analysis whereas 236 were included in the tolerability analysis. The subjects recruited to the study were required to fill up the Psychological General Well-Being Index (PGWBI). RESULTS: There was no significant change in body weight or blood pressure throughout the treatment. Adverse events reported by patients during treatment consisted of those already known to be associated with oral contraceptive use. PGWBI scores were significantly higher after six cycles of treatment compared with baseline values (p<.0001). A total of 198 (84.2%) subjects reported a great improvement in premenstrual symptoms. CONCLUSIONS: The results of this study confirm that oral use of a combination of ethinylestradiol 30 microg and drospirenone 3 mg provides good cycle control, is well tolerated and has a positive impact on symptoms of premenstrual disorder.