63 research outputs found

    New binary solid dispersion of indomethacin and croscarmellose sodium: physical characterization and in vitro dissolution enhancement

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    Solid dispersions (SDx) containing Indomethacin (IND), a poorly water-soluble drug, and the disintegrant excipient sodium croscarmellose (SC) were prepared by a co-drying method and characterized by Infrared spectroscopy (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). An FT-IR analysis performed on IND-SC solid dispersion and their physical mixtures indicated that IND does not interact with SC in the solid state. An analysis of the information produced by DSC, XRD, and SEM confirmed that the crystalline α-form of IND was homogeneously incorporated into SDx. IND release from SDx was significantly greater than that from its corresponding physical mixtures with the high homogeneous molecular dispersion and the crystalline modification of IND appearing to be the cause. This behavior may have a beneficial effect on the biopharmaceutical performance of this drug

    Angiotensin type 1A receptors in C1 neurons of the rostral ventrolateral medulla modulate the pressor response to aversive stress

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    The rise in blood pressure during an acute aversive stress has been suggested to involve activation of angiotensin type 1A receptors (AT(1A)Rs) at various sites within the brain, including the rostral ventrolateral medulla. In this study we examine the involvement of AT(1A)Rs associated with a subclass of sympathetic premotor neurons of the rostral ventrolateral medulla, the C1 neurons. The distribution of putative AT(1A)R-expressing cells was mapped throughout the brains of three transgenic mice with a bacterial artificial chromosome-expressing green fluorescent protein under the control of the AT(1A)R promoter. The overall distribution correlated with that of the AT(1A)Rs mapped by other methods and demonstrated that the majority of C1 neurons express the AT(1A)R. Cre-recombinase expression in C1 neurons of AT(1A)R-floxed mice enabled demonstration that the pressor response to microinjection of angiotensin II into the rostral ventrolateral medulla is dependent upon expression of the AT(1A)R in these neurons. Lentiviral-induced expression of wild-type AT(1A)Rs in C1 neurons of global AT(1A)R knock-out mice, implanted with radiotelemeter devices for recording blood pressure, modulated the pressor response to aversive stress. During prolonged cage-switch stress, expression of AT(1A)Rs in C1 neurons induced a greater sustained pressor response when compared to the control viral-injected group (22 +/- 4 mmHg for AT(1A)R vs 10 +/- 1 mmHg for GFP; p < 0.001), which was restored toward that of the wild-type group (28 +/- 2 mmHg). This study demonstrates that AT(1A)R expression by C1 neurons is essential for the pressor response to angiotensin II and that this pathway plays an important role in the pressor response to aversive stress

    Moderate Physical Training Ameliorates Cardiovascular Dysfunction Induced by High Fat Diet After Cessation of Training in Adult Rats

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    We aimed to test whether moderate physical training can induce long-lasting protection against cardiovascular risk factors induced by high fat diet (HFD) intake, even after cessation of training. 90-days-old Wistar rats were submitted to a sedentary lifestyle or moderate physical training, three times a week, for 30 days. Following this, at 120 days-of age, sedentary and trained rats received a hypercaloric diet (HFD) or a commercial diet normal fat diet (NFD) for 30 days. Body weight (BW) and food intake were evaluated weekly. At 150 days-of age, hemodynamic measures (systolic, diastolic, mean blood pressure, pulse pressure, pulse interval and heart rate) were made via an indwelling femoral artery catheter. Beat-to-beat data were analyzed to calculate power spectra of systolic blood pressure (SBP) and pulse interval. After euthanasia, mesenteric fat pads were removed and weighted and total blood was stored for later analysis of lipid profile. Consumption of a HFD increased blood pressure (BP), pulse pressure, low frequency BP variability, BW gain, fat pad stores and induced dyslipidemia. Interestingly, prior physical training was able to partially protect against this rise in BP and body fat stores. Prior physical training did not totally protect against the effects of HFD consumption but previously trained animals did demonstrate resistance to the development of cardiometabolic alterations, which illustrate that the benefits of physical training may be partially maintained even after 30 days of detraining period

    Effect of different etching time on the bond strength of ZLS ceramic / Efeito de diferentes tempos de condicionamento na resistência de união da cerâmica ZLS

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    Objetivo: Avaliar o efeito de diferentes tempos de condicionamento com ácido fluorídrico (HF) a 5% e 10%, na resistência de união do cimento resinoso (RC) a uma cerâmica de silicato de lítio reforçada com zircônia (ZLS). Metodologia: 64 fatias de cerâmica foram divididas em 8 grupos (n=8) de acordo com o condicionamento ácido em diferentes tempos e concentrações (5% por 20, 30, 40 e 60s, e 10% por 10, 20, 30 e 40s). Após delimitação da área adesiva na cerâmica, foi aplicado o silano RelyX Ceramic Primer e o adesivo Single Bond Universal. O cimento resinoso RelyX Ultimate, foi inserido em uma matriz de teflon e fotopolimerizado sobre a superfície cerâmica durante 40 s, os espécimes, então, foram armazenados em água deionizada a 37°C por 24 h e submetidos ao teste de µSBS. Resultados: O tratamento 5%/20s exibiu estatisticamente a menor resistência de união 21,96 MPa (p&lt;0.01), diferindo do tratamento com HF a 10% nos quatro tempos estudados: 10s = 29,59 MPa, 20s = 29,77 MPa, 30s = 29,68 MPa e 40s = 30,78 MPa (p&lt;0.01); o tratamento 10%/40s exibiu a maior resistência de união (30,78 MPa), diferindo apenas do 5%/20s (21,96 MPa), Conclusão: A cerâmica ZLS, condicionada com HF 5% por 30s ou HF 10% por 10 e 20s, exibiu maior resistência de união do que o protocolo do fabricante.

    Optimization of lipase production by solid-state fermentation of olive pomace: from flask to laboratory-scale packed-bed bioreactor

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    Lipases are versatile catalysts with many applications and can be produced by solid-state fermentation (SSF) using agro-industrial wastes. The aim of this work was to maximize the production of Aspergillus ibericus lipase under SSF of olive pomace (OP) and wheat bran (WB), evaluating the effect on lipase production of C/N ratio, lipids, phenols, content of sugars of substrates and nitrogen source addition. Moreover, the implementation of the SSF process in a packed-bed bioreactor and the improvement of lipase extraction conditions were assessed. Low C/N ratios and high content of lipids led to maximum lipase production. Optimum SSF conditions were achieved with a C/N mass ratio of 25.2 and 10.2% (w/w) lipids in substrate, by the mixture of OP:WB (1:1) and supplemented with 1.33% (w/w) (NH4)2SO4. Studies in a packed-bed bioreactor showed that the lower aeration rates tested prevented substrate dehydration, improving lipase production. In this work, the important role of Triton X-100 on lipase extraction from the fermented solid substrate has been shown. A final lipase activity of 223 ± 5 U g1 (dry basis) was obtained after 7 days of fermentation.Felisbela Oliveira acknowledges the financial support from Fundação para a Ciência e Tecnologia (FCT) of Portugal through grant SFRH/BD/87953/2012. José Manuel Salgado was supported by grant CEB/N2020–INV/01/2016 from Project ‘‘BIOTECNORTE-Underpinning Biotechnology to foster the north of Portugal bioeconomy’’ (NORTE-01-0145-FEDER-000004). Luı ´s Abrunhosa was supported by grant UMINHO/BPD/51/2015 from project UID/BIO/04469/2013 financed by FCT/MEC (OE). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER006684) and BioTecNorte operation (NORTE-01-0145-FEDER000004) funded by the European Regional Development Fund under the scope of Norte2020–Programa Operacional Regional do Norte. Noelia Pérez-Rodríguez acknowledges the financial support of FPU fellowship from the Spanish Ministry of Education, Culture and Sports. The authors thank the Spanish Ministry of Economy and Competitiveness for the financial support of this work (Project CTQ2015-71436-C2-1-R), which has partial financial support from the FEDER funds of the European Union.info:eu-repo/semantics/publishedVersio

    Modeling the differentiation of A- and C-type baroreceptor firing patterns

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    The baroreceptor neurons serve as the primary transducers of blood pressure for the autonomic nervous system and are thus critical in enabling the body to respond effectively to changes in blood pressure. These neurons can be separated into two types (A and C) based on the myelination of their axons and their distinct firing patterns elicited in response to specific pressure stimuli. This study has developed a comprehensive model of the afferent baroreceptor discharge built on physiological knowledge of arterial wall mechanics, firing rate responses to controlled pressure stimuli, and ion channel dynamics within the baroreceptor neurons. With this model, we were able to predict firing rates observed in previously published experiments in both A- and C-type neurons. These results were obtained by adjusting model parameters determining the maximal ion-channel conductances. The observed variation in the model parameters are hypothesized to correspond to physiological differences between A- and C-type neurons. In agreement with published experimental observations, our simulations suggest that a twofold lower potassium conductance in C-type neurons is responsible for the observed sustained basal firing, whereas a tenfold higher mechanosensitive conductance is responsible for the greater firing rate observed in A-type neurons. A better understanding of the difference between the two neuron types can potentially be used to gain more insight into the underlying pathophysiology facilitating development of targeted interventions improving baroreflex function in diseased individuals, e.g. in patients with autonomic failure, a syndrome that is difficult to diagnose in terms of its pathophysiology.Comment: Keywords: Baroreflex model, mechanosensitivity, A- and C-type afferent baroreceptors, biophysical model, computational mode

    A high fat diet during adolescence in male rats negatively programs reproductive and metabolic function which is partially ameliorated by exercise

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    An interaction between obesity, impaired glucose metabolism and sperm function in adults has been observed but it is not known whether exposure to a diet high in fat during the peri-pubertal period can have longstanding programmed effects on reproductive function and gonadal structure. This study examined metabolic and reproductive function in obese rats programmed by exposure to a high fat (HF) diet during adolescence. The effect of physical training (Ex) in ameliorating this phenotype was also assessed. Thirty-day-old male Wistar rats were fed a HF diet (35% lard w/w) for 30 days then subsequently fed a normal fat diet (NF) for a 40-day recovery period. Control animals were fed a NF diet throughout life. At 70 days of life, animals started a low frequency moderate exercise training that lasted 30 days. Control animals remained sedentary (Se). At 100 days of life, biometric, metabolic and reproductive parameters were evaluated. Animals exposed to HF diet showed greater body weight, glucose intolerance, increased fat tissue deposition, reduced VO 2max and reduced energy expenditure. Consumption of the HF diet led to an increase in the number of abnormal seminiferous tubule and a reduction in seminiferous epithelium height and seminiferous tubular diameter, which was reversed by moderate exercise. Compared with the NF-Se group, a high fat diet decreased the number of seminiferous tubules in stages VII-VIII and the NF-Ex group showed an increase in stages XI-XIII. HF-Se and NF-Ex animals showed a decreased number of spermatozoa in the cauda epididymis compared with animals from the NF-Se group. Animals exposed to both treatments (HF and Ex) were similar to all the other groups, thus these alterations induced by HF or Ex alone were partially prevented. Physical training reduced fat pad deposition and restored altered reproductive parameters. HF diet consumption during the peri-pubertal period induces long-term changes on metabolism and the reproductive system, but moderate and low frequency physical training is able to recover adipose tissue deposition and reproductive system alterations induced by high fat diet. This study highlights the importance of a balanced diet and continued physical activity during adolescence, with regard to metabolic and reproductive health

    How do cardiologists select patients for dual antiplatelet therapy continuation beyond 1 year after a myocardial infarction? Insights from the EYESHOT Post-MI Study

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    Background: Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). Hypothesis: We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. Methods: We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. Results: Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. Conclusions: Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI

    <b>A evolução da farmacovigilância no Brasil</b> - DOI: 10.4025/actascihealthsci.v27i2.1377 <b>The evolution of the pharmacovigilance in Brazil</b> - DOI: 10.4025/actascihealthsci.v27i2.1377

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    Este trabalho faz um breve relato sobre os aspectos conceituais e os marcos históricos que envolvem a Farmacovigilância. São abordados os caminhos que levaram ao desenvolvimento da Farmacovigilância no mundo e no Brasil, finalizando com as perspectivas da formação de um serviço de qualidade que contribuirá para minimizar os potenciais danos dos medicamentos e assim servir à saúde pública e aumentar o senso de confiança dos pacientes nos medicamentos<br>This work makes a brief story on the conceptual aspects and the historical landmarks that involve the Pharmacovigilance. There are related the ways that had taken the development of the Pharmacovigilance in the world and Brazil, concluding with the perspectives of the development of a qualified service that will contribute to minimize the injury caused by drugs use and so serving to the public health and increasing the reliable sense of the patients in drugs us
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