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21.
Eno powder (GlaxoSmithKline), an antacid preparation readily available over the counter, was used instead of a CO(2) generator for the growth of 15 strains of Neisseria gonorrhoeae obtained from men with urethritis. Due to its easy accessibility and low cost, Eno powder can be useful in developing countries for transporting clinical specimens from resource-poor peripheral labs to reference laboratories. 相似文献
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Non‐peptide‐based new class of platelet aggregation inhibitors: Design,synthesis, bioevaluation,SAR, and in silico studies
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Pradeep K. Jaiswal Vashundhra Sharma Surendra Kumar Manas Mathur Ajit K. Swami Dharmendra K. Yadav Sandeep Chaudhary 《Archiv der Pharmazie》2018,351(3-4)
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Restless leg syndrome (RLS) is a common disorder causing sleep impairment. Antipsychotics particularly belonging to the first generation are a common cause of RLS. Whereas, RLS induced by olanzapine is rare, there are only a few cases reported earlier. We report a 38-year-old lady suffering from persistent delusional disorder who was prescribed olanzapine. She developed RLS after initiation of olanzapine which improved when switched over to risperidone. This report will caution clinicians about this side effect of a very commonly prescribed antipsychotic drug.KEY WORDS: Olanzapine, restless legs syndrome 相似文献
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Raches Ella Krishna Mohan Vadrevu Harsh Jogdand Sai Prasad Siddharth Reddy Vamshi Sarangi Brunda Ganneru Gajanan Sapkal Pragya Yadav Priya Abraham Samiran Panda Nivedita Gupta Prabhakar Reddy Savita Verma Sanjay Kumar Rai Chandramani Singh Sagar Vivek Redkar Chandra Sekhar Gillurkar Balram Bhargava 《The Lancet infectious diseases》2021,21(5):637-646
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Vikash K. Yadav Rahul S. Mandal Bhanwar L. Puniya Rahul Kumar Sharmistha Dey Sarman Singh Savita Yadav 《Chemical biology & drug design》2015,85(3):404-410
SAP-1 is a low molecular weight cysteine protease inhibitor (CPI) which belongs to type-2 cystatins family. SAP-1 protein purified from human seminal plasma (HuSP) has been shown to inhibit cysteine and serine proteases and exhibit interesting biological properties, including high temperature and pH stability. Heparin is a naturally occurring glycosaminoglycan (with varied chain length) which interacts with a number of proteins and regulates multiple steps in different biological processes. As an anticoagulant, heparin enhances inhibition of thrombin by the serpin antithrombin III. Therefore, we have employed surface plasmon resonance (SPR) to improve our understanding of the binding interaction between heparin and SAP-1 (protease inhibitor). SPR data suggest that SAP-1 binds to heparin with a significant affinity (KD = 158 nm ). SPR solution competition studies using heparin oligosaccharides showed that the binding of SAP-1 to heparin is dependent on chain length. Large oligosaccharides show strong binding affinity for SAP-1. Further to get insight into the structural aspect of interactions between SAP-1 and heparin, we used modelled structure of the SAP-1 and docked with heparin and heparin-derived polysaccharides. The results suggest that a positively charged residue lysine plays important role in these interactions. Such information should improve our understanding of how heparin, present in the reproductive tract, regulates cystatins activity. 相似文献
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Archana Swami Michaela R. Reagan Pamela Basto Yuji Mishima Nazila Kamaly Siobhan Glavey Sufeng Zhang Michele Moschetta Dushanth Seevaratnam Yong Zhang Jinhe Liu Masoumeh Memarzadeh Jun Wu Salomon Manier Jinjun Shi Nicolas Bertrand Zhi Ning Lu Kenichi Nagano Roland Baron Antonio Sacco Aldo M. Roccaro Omid C. Farokhzad Irene M. Ghobrial 《Proceedings of the National Academy of Sciences of the United States of America》2014,111(28):10287-10292
Bone is a favorable microenvironment for tumor growth and a frequent destination for metastatic cancer cells. Targeting cancers within the bone marrow remains a crucial oncologic challenge due to issues of drug availability and microenvironment-induced resistance. Herein, we engineered bone-homing polymeric nanoparticles (NPs) for spatiotemporally controlled delivery of therapeutics to bone, which diminish off-target effects and increase local drug concentrations. The NPs consist of poly(d,l-lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), and bisphosphonate (or alendronate, a targeting ligand). The engineered NPs were formulated by blending varying ratios of the synthesized polymers: PLGA-b-PEG and alendronate-conjugated polymer PLGA-b-PEG-Ald, which ensured long circulation and targeting capabilities, respectively. The bone-binding ability of Ald-PEG-PLGA NPs was investigated by hydroxyapatite binding assays and ex vivo imaging of adherence to bone fragments. In vivo biodistribution of fluorescently labeled NPs showed higher retention, accumulation, and bone homing of targeted Ald-PEG-PLGA NPs, compared with nontargeted PEG-PLGA NPs. A library of bortezomib-loaded NPs (bone-targeted Ald-Bort-NPs and nontargeted Bort-NPs) were developed and screened for optimal physiochemical properties, drug loading, and release profiles. Ald-Bort-NPs were tested for efficacy in mouse models of multiple myeloma (MM). Results demonstrated significantly enhanced survival and decreased tumor burden in mice pretreated with Ald-Bort-NPs versus Ald-Empty-NPs (no drug) or the free drug. We also observed that bortezomib, as a pretreatment regimen, modified the bone microenvironment and enhanced bone strength and volume. Our findings suggest that NP-based anticancer therapies with bone-targeting specificity comprise a clinically relevant method of drug delivery that can inhibit tumor progression in MM.The incidence of bone metastasis is common in 60–80% of cancer patients (1). During bone metastasis, cancer cells induce a sequence of changes in the microenvironment such as secreting cytokines to increase the activity of osteoclasts via the parathyroid hormone-related protein (PTHrP), receptor activator of nuclear factor-κB ligand (RANKL), and interleukin-6 (IL-6), resulting in increased bone resorption and secretion of growth factors from the bone matrix (2). This creates a “vicious cycle” of bone metastasis, where bone marrow becomes packed with cancer cells that develop resistance to conventional chemotherapy, and leads to devastating consequences of bone fractures, pain, hypercalcaemia, and spinal cord and nerve compression syndromes (2, 3). Multiple myeloma (MM) is a plasma cell cancer that proliferates primarily in bone marrow and causes osteolytic lesions (1). Antiresorption agents, such as bisphosphonates, may alleviate bone pain, but they are ineffective at inducing bone healing or osteogenesis in MM patients (4).Bortezomib is a proteasome inhibitor that has shown marked antitumor effects in patients with MM. Proteasome inhibitors, such as bortezomib, are also effective at increasing bone formation, both preclinically and clinically (5–9). However, the major drawback of bortezomib use in early stages of MM development is its toxicity, specifically, peripheral neuropathy (5). Therefore, we aimed to develop a method to deliver bortezomib with decreased off-target side effects by using bone-specific, bortezomib-loaded nanoparticles (NPs). The NP system was based on biodegradable, biocompatible, and Food and Drug Administration (FDA)-approved components, which are both clinically and translationally relevant. NPs derived from poly(d,l-lactic-co-glycolic acid) (PLGA), a controlled release polymer system, are an excellent choice because their safety in the clinic is well established (10, 11). Polyethylene glycol (PEG)-functionalized PLGA NPs are especially desirable as PEGylated polymeric NPs have significantly reduced systemic clearance compared with similar particles without PEG (12, 13). A number of FDA-approved drugs in clinical practice use PEG for improved pharmaceutical properties such as enhanced circulation in vivo (12, 13). To target NPs to bone [rich in the mineral hydroxyapatite (HA)], the calcium ion-chelating molecules of bisphosphonates represent a promising class of ligands (14). Bisphosphonates, upon systemic administration, are found to deposit in bone tissue, preferentially at the high bone turnover sites, such as the metastatic bone lesions, with minimal nonspecific accumulation (14) and were used herein to deliver NPs to the bone.A few systems explored for MM treatment have been tested in vitro including the following: (i) snake venom and silica NPs (15); (ii) thymoquinone and PLGA-based particles (16); (iii) curcumin and poly(oxyethylene) cholesteryl ether (PEG-Chol) NPs (17), polyethylenimine-based NPs for RNAi in MM (18), paclitaxel-Fe3O4 NPs (19), and liposomes (20). However, none of the above-mentioned systems have aimed to manipulate the bone marrow microenvironment rather than the myeloma cells directly (21). To date, there are no reports of using bone-targeted, controlled release, polymeric NPs with stealth properties for MM therapy. In this study, we designed NPs bearing three main components: (i) a targeting element that can selectively bind to bone mineral; (ii) a layer of stealth (PEG) to minimize immune recognition and enhance circulation; and (iii) a biodegradable polymeric material, forming an inner core, that can deliver therapeutics and/or diagnostics in a controlled manner. In this study, the physicochemical properties of a range of NPs was investigated (including NP size, charge, targeting ligand density, drug loading, and drug release kinetics) and an optimal formulation with ideal properties and maximal drug encapsulation was used for in vivo efficacy studies. We fine-tuned the NP targeting ligand density to optimize its bone-binding ability and further investigated its application for targeting myeloma in the bone microenvironment. We believe our NP system has the potential to increase drug availability by improving pharmacokinetics and biodistribution that can provide bone microenvironment specificity, which may increase the therapeutic window and most certainly decrease the off-target effects (12, 13). 相似文献
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Surya Porwal Shikha Tewari Rajinder K. Sharma Savita Rani Singhal Satish C. Narula 《Journal of periodontology》2014,85(10):1380-1389
Background: Recently, some studies have revealed the effect of polycystic ovary syndrome (PCOS) on gingival inflammation. This cross‐sectional study attempts to assess the periodontal status and systemic inflammation of women receiving medical treatment for PCOS and women newly diagnosed with PCOS. Methods: A total of 126 participants comprising 41 newly diagnosed patients with PCOS (PCOS‐N), 45 patients with PCOS on medical treatment (PCOS‐MT), and 40 systemically healthy controls (control group [CG]) were examined. Periodontal parameters, anthropometric parameters, and serum levels of high‐sensitivity C‐reactive protein (hsCRP) were recorded. Results: Women with newly diagnosed PCOS had increased sites with bleeding on probing (BOP), probing depth, clinical attachment level (CAL), waist circumference (WC), hsCRP, and prevalence of periodontitis compared with control and PCOS‐MT groups (P ≤0.05). On partial correlation analysis after controlling for confounders, BOP and CAL correlated positively and significantly with hsCRP (P = 0.01 and P = 0.005). Multivariate linear regression analysis revealed that BOP and CAL (dependent variable) (P = 0.009/R2 = 0.05 and P = 0.005/R2 = 0.07, respectively) had significant association with hsCRP. Furthermore, hsCRP, when considered as outcome, also exhibited association with CAL and WC (P = 0.002/R2 = 0.07 and P = 0.04/R2 = 0.106). Logistic regression analysis demonstrated that the PCOS‐N group had 2.88 times increased likelihood of having moderate periodontitis (adjusted odds ratio 2.88, 95% confidence interval 1.18 to 6.98). Conclusions: Women with newly diagnosed PCOS may have increased prevalence and likelihood for periodontitis, with higher measures of periodontal inflammation and breakdown than those on medical treatment for PCOS and systemically healthy females. Furthermore, periodontal breakdown might depend on systemic inflammation and vice versa. 相似文献