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101.
Janine Braga de Souza Jacqueline de Souza Lara Maria Lopes de Castro Melissa Fabíola Siqueira Ranylson Marcello Leal Savedra 《Pharmaceutical development and technology》2019,24(3):283-292
This study aimed at evaluating the shake-flask use as a universal method to evaluate drug solubility in a biowaiver context as proposed by FDA, EMA and ANVISA. The solubility of losartan was determined in three buffers using the shake-flask method, intrinsic dissolution (ID) and Quantum Chemistry. Moreover, the evaluation of a losartan dissolution profile from coated tablets was conducted. The losartan low solubility in pH 1.2 and high solubility in pH 6.8 were observed using the shake-flask method. However, the solubility results using ID demonstrated its high solubility in pH 1.2 and 6.8. It was not possible to find conclusive results regarding the solubility of the drug in pH 4.5. The studies conducted by Quantum Chemistry provide molecular and electronic data that helped understand the losartan solvation in different pH values. Our experimental results defined that losartan can be classified as a low-solubility drug. In addition, this work shows that shake-flask cannot be a universal method of solubility studies in biowaiver context. Individual analysis will be necessary. The intrinsic dissolution should be considered as a complementary method. 相似文献
102.
Francesco Venturelli Giuliano Carrozzi Letizia Sampaolo Lara Bolognesi Sandro Baldissera Nicoletta Bertozzi Stefano Campostrini Benedetta Contoli Gianluigi Ferrante Maria Masocco Valentina Minardi Angelo D'Argenzio Pirous F Moghadam Luana Penna Alberto Perra Elisa Quarchioni Mauro Ramigni Massimo O Trinito Stefania Salmaso 《Lancet》2014
BackgroundInfluenza is an important public health problem, with potential severe consequences among people with chronic diseases. The aim of this study was to obtain reliable measures of seasonal influenza vaccine uptake in this population, otherwise not available in Italy.MethodsProgressi delle Aziende Sanitarie per la Salute in Italia (PASSI) is a nationwide surveillance system of health-related behaviours and acceptance of preventive interventions (including influenza immunisation) offered by the Italian National Health Service. Data are collected with telephone interviews at local health unit level for supporting local activities. The survey sample is randomly selected from local health unit lists of adult residents. The trend of annual vaccine coverage since 2008 was estimated for people aged 18–64 years who reported having at least one chronic disease. To obtain a sufficient sample size in subgroups, we analysed the characteristics of vaccinated people in the 2010–13 cumulative dataset. Univariate, multivariate, and logistic regression analyses were undertaken.FindingsIn 2008–13, 13 659 individuals with at least one chronic disease were interviewed. Vaccination coverage fell significantly from 29·7% (95% CI 27·2–32·4) in 2007–08 to 19·9% (18·0–22·1) in 2012–13. During 2010–13, the overall proportion of vaccinated people with a chronic disease was 25·6% (24·5–26·7). Vaccine coverage of people with diabetes (34·3%, 31·7–36·9) or cardiovascular diseases (31·8%, 29·6–34·2) was greater than that of people affected by renal failure, respiratory diseases, tumours, or chronic liver diseases (26·5% [22·5–30·7], 24·9% [23·2–26·7], 22·2% [20·0–24·6], and 20·6% [17·5–24·6], respectively). Vaccination coverage increased with age (from 13·1% [11·0–15·5] in the 18–34 year age group to 33·4% [31·9–35·1] in people aged 50–64 years); it was higher among people with a low educational level than among those with a high educational level, higher in those having economic difficulties than in those with no economic difficulties, and higher among Italian citizens than among non-citizens.InterpretationIn the past few years, prevalence of influenza vaccination in Italian adults with at least one chronic disease was well below the Ministry of Health's goal (75% minimum) and showed a downward trend. A major reason of this evolution is probably the changing public perception of the benefits and risks of vaccines. PASSI is a source of useful data not otherwise available for public health intervention.FundingItalian Ministry of Health. 相似文献
103.
S. A. Hiles E. S. Harvey V. M. McDonald M. Peters P. Bardin P. N. Reynolds J. W. Upham M. Baraket Z. Bhikoo J. Bowden B. Brockway L. P. Chung B. Cochrane G. Foxley J. Garrett M. Hew L. Jayaram C. Jenkins C. Katelaris G. Katsoulotos M. S. Koh V. Kritikos M. Lambert D. Langton A. Lara Rivero G. B. Marks P. G. Middleton A. Nanguzgambo N. Radhakrishna H. Reddel J. Rimmer A. M. Southcott M. Sutherland F. Thien P. A. B. Wark I. A. Yang E. Yap P. G. Gibson 《Clinical and experimental allergy》2018,48(6):650-662
104.
Chelsea Eason MSCR Ahmad Aleisa MD Julie R. Jones PhD Eloise J. Prijoles MD Lara Wine Lee MD PhD 《Pediatric dermatology》2020,37(5):915-917
FILS syndrome (facial dysmorphism, immunodeficiency, livedo, and short stature) is a rare autosomal recessive disorder caused by pathogenic alterations in the POLE gene leading to multisystemic manifestations, including poorly characterized skin findings. We report a child with a homozygous variant, c.100C > T (p.Arg34Cys), in POLE and features consistent with poikiloderma, expanding the dermatologic signs associated with this rare disorder. Additionally, we review reported cases of FILS syndrome, discuss possible pathomechanisms for our patient's presentation, and consider implications for management. 相似文献
105.
Jennifer Noad Laura E. Gonzalez‐Lara Heather C. Broughton Catherine McFadden Yuhua Chen David A. Hess Paula J. Foster 《NMR in biomedicine》2013,26(4):458-467
Peripheral arterial disease is a clinical problem in which mesenchymal stromal cell (MSC) transplantation may offer substantial benefit by promoting the generation of new blood vessels and improving limb ischemia and wound healing via their potent paracrine activities. MRI allows for the noninvasive tracking of cells over time using iron oxide contrast agents to label cells before they are injected or transplanted. However, a major limitation of the tracking of iron oxide‐labeled cells with MRI is the possibility that dead or dying cells will transfer the iron oxide label to local bystander macrophages, making it very difficult to distinguish between viable transplanted cells and endogenous macrophages in the images. In this study, a severely immune‐compromised mouse, with limited macrophage activity, was investigated to examine cell tracking in a system in which bystander cell uptake of dead, iron‐labeled cells or free iron particles was minimized. MRI was used to track the fate of MSCs over 21 days after their intramuscular transplantation in mice with a femoral artery ligation. In all mice, a region of signal loss was observed at the injection site and the volume of signal hypointensity diminished over time. Fluorescence and light microscopy showed that iron‐positive MSCs persisted at the transplant site and often appeared to be integrated in perivascular niches. This was compared with MSC transplantation in immune‐competent mice with femoral artery ligation. In these mice, the regions of signal loss caused by iron‐labeled MSC cleared more slowly, and histology revealed iron particles trapped at the site of cell transplantation and associated with areas of inflammation. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
106.
Pompe disease is a rare and deadly muscle disorder. As a clinical entity, the disease has been known for over 75 years. While an optimist might be excited about the advances made during this time, a pessimist would note that we have yet to find a cure. However, both sides would agree that many findings in basic science—such as the Nobel prize-winning discoveries of glycogen metabolism, the lysosome, and autophagy—have become the foundation of our understanding of Pompe disease. The disease is a glycogen storage disorder, a lysosomal disorder, and an autophagic myopathy. In this review, we will discuss how these past discoveries have guided Pompe research and impacted recent therapeutic developments. 相似文献
107.
Manoela Viar Fogaça Lucas Milanez Benicio Lara Martinelli Zapata Priscilla de Freitas Cardoso Marcelo Tempesta de Oliveira 《Pharmaceutical biology》2017,55(1):2005-2014
Context: Indigofera suffruticosa Miller (Fabaceae) and I. truxillensis Kunth produce compounds, such as isatin (ISA) and indirubin (IRN), which possess antitumour properties. Their effects in mammalian cells are still not very well understood.Objective: We evaluated the activities of ISA and/or IRN on cell viability and apoptosis in vitro, their genotoxic potentials in vitro and in vivo, and the IRN- and ISA-induced expression of ERCC1 or BAX genes.Materials and methods: HeLa and/or CHO-K1 cell lines were tested (3 or 24?h) in the MTT, Trypan blue exclusion, acridine orange/ethidium bromide, cytokinesis-blocked micronucleus (CBMN) and comet (36, 24 and 72?h) tests after treatment with IRN (0.1 to 200?μM) or ISA (0.5 to 50?μM). Gene expression was measured by RT-qPCR in HeLa cells. Swiss albino mice received IRN (3, 4 or 24?h) by gavage (50, 100 and 150?mg/kg determined from the LD50 – 1?g/kg b.w.) and submitted to comet assay in vivo.Results: IRN reduced the viability of CHO-K1 (24?h; 5 to 200?μM) and HeLa cells (10 to 200?μM), and was antiproliferative in the CBMN test (CHO-K1: 0.5 to 10?μM; HeLa: 5 and 10?μM). The drug did not induce apoptosis, micronucleus neither altered gene expression. IRN and ISA were genotoxic for HeLa cells (3 and 24?h) at all doses tested. IRN (100 and 150?mg/kg) also induced genotoxicity in vivo (4?h).Conclusion: IRN and ISA have properties that make them candidates as chemotherapeutics for further pharmacological investigations. 相似文献
108.
109.
We examined the therapeutic process of grief change in survivors of suicide participating in complicated grief group therapy (CGGT) using the meaning of loss codebook (MLC). Complicated grief group therapy is a multimodal group psychotherapy designed to restore normal grieving in persons with complicated grief. Using video data, we evaluated transition points in psychotherapy associated with meaning reconstruction: retelling the narrative of the death, having an imaginal conversation with the deceased, and memory integration. The MLC codes captured most of the voiced statements of participants, provided a valuable lens for articulating the therapeutic process, and affirmed that CGGT facilitated effective grief. 相似文献
110.