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https://www.readbyqxmd.com/read/28806519/pluronic-p85-f68-micelles-of-baicalein-could-interfere-with-mitochondria-to-overcome-mrp2-mediated-efflux-and-offer-improved-anti-parkinsonian-activity
#1
Tongkai Chen, Ye Li, Chuwen Li, Xiang Yi, Ruibing Wang, Simon Ming Yuen Lee, Ying Zheng
Overexpression of the drug efflux transporter multidrug resistance-associated protein 2 (MRP2) in the gastrointestinal tract and blood-brain barrier compromises the oral delivery of drugs to the circulation system and brain in the treatment of Parkinson's disease (PD). In this study, we aim to develop small-sized Pluronic P85/F68 micelles loaded with baicalein (B-MCs) to overcome MRP2-mediated efflux and to investigate related mechanism, as well as the anti-Parkinsonian efficacy. Spherical and sustained-release B-MCs have a mean particle size of 40...
August 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28806082/the-discovery-of-novel-antimalarial-aminoxadiazoles-as-a-promising-nonendoperoxide-scaffold
#2
Elena Sandoval, María José Lafuente-Monasterio, María J Almela, Pablo Castañeda, María Belén Jiménez Díaz, María S Martínez-Martínez, Jaume Vidal, Íñigo Angulo-Barturen, Paul Bamborough, Jeremy Burrows, Nicholas Cammack, María J Chaparro, José M Coterón, Cristina de Cozar, Benigno Crespo, Beatriz Díaz, Gerard Drewes, Esther Fernández, Santiago Ferrer-Bazaga, María Teresa Fraile, Francisco J Gamo, Sonja Ghidelli-Disse, Rubén Gómez, John Haselden, Sophie Huss, María Luisa León, Jaime de Mercado, Simon J F Macdonald, José Ignacio Martín Hernando, Sara Prats, Margarita Puente, Anne Rodríguez, Juan C de la Rosa, Lourdes Rueda, Carolyn Selenski, Paul Willis, David M Wilson, Michael Witty, Félix Calderón
Since the appearance of resistance to the current front-line antimalarial treatments, ACTs (artemisinin combination therapies), the discovery of novel chemical entities to treat the disease is recognized as a major global health priority. From the GSK antimalarial set, we identified an aminoxadiazole with an antiparasitic profile comparable with artemisinin (1), with no cross-resistance in a resistant strains panel and a potential new mode of action. A medicinal chemistry program allowed delivery of compounds such as 19 with high solubility in aqueous media, an acceptable toxicological profile, and oral efficacy...
August 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28806057/rational-design-and-multi-biological-profiling-of-novel-donepezil-trolox-hybrids-against-alzheimer-s-disease-with-cholinergic-antioxidant-neuroprotective-and-cognition-enhancing-properties
#3
Pei Cai, Si-Qiang Fang, Xue-Lian Yang, Jia-Jia Wu, Qiao-Hong Liu, Hao Hong, Xiao-Bing Wang, Lingyi Kong
A novel series of donepezil-trolox hybrids were designed, synthesized and evaluated as multifunctional ligands against Alzheimer's disease (AD). Biological assays showed that these derivatives possessed moderate to good inhibitory activities against acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B) as well as remarkable antioxidant effects. The optimal compound 6d exhibited balanced functions with good inhibition against hAChE (IC50 = 0.54 μM) and hMAO-B (IC50 = 4.3 μM), significant antioxidant activity (41...
August 14, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28806011/a-primer-on-bleeding-risk-and-management-strategies-of-newer-oral-anti-platelet-agents-in-cardiovascular-disease
#4
Jimmy Yee, Vishesh Kumar, Amornpol Anuwatworn, Marian Petrasko, Adam Stys
Aspirin, the first antiplatelet agent, has been around since the 19th century, and is one of the most established drugs in history. With the improvement of coronary interventions in the past few decades, there has been more reliance on oral antiplatelet agents to reduce complications of in-stent restenosis/thrombosis. Clopidogrel was initially introduced in 1997, and within the past seven years, two additional oral antiplatelet agents have been approved by the U.S. Food and Drug Administration. With more potent antiplatelet agents comes increased risks of adverse effects...
October 2016: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28805809/x-ray-structures-of-endothelin-etb-receptor-bound-to-clinical-antagonist-bosentan-and-its-analog
#5
Wataru Shihoya, Tomohiro Nishizawa, Keitaro Yamashita, Asuka Inoue, Kunio Hirata, Francois Marie Ngako Kadji, Akiko Okuta, Kazutoshi Tani, Junken Aoki, Yoshinori Fujiyoshi, Tomoko Doi, Osamu Nureki
Endothelin receptors (ETRs) have crucial roles in vascular control and are targets for drugs designed to treat circulatory-system diseases and cancer progression. The nonpeptide dual-ETR antagonist bosentan is the first oral drug approved to treat pulmonary arterial hypertension. Here we report crystal structures of human endothelin ETB receptor bound to bosentan and to the ETB-selective analog K-8794, at 3.6-Å and 2.2-Å resolution, respectively. The K-8794-bound structure reveals the detailed water-mediated hydrogen-bonding network at the transmembrane core, which could account for the weak negative allosteric modulation of ETB by Na(+) ions...
August 14, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28805592/nonmotor-effects-of-conventional-and-transdermal-dopaminergic-therapies-in-parkinson-s-disease
#6
Ryul Kim, Beomseok Jeon
Nonmotor symptoms (NMS) are an integral component of Parkinson's disease (PD). Because the burden and range of NMS are key determinants of quality of life for patients and caregivers, their management is a crucial issue in clinical practice. Although a range of NMS have a dopaminergic pathophysiological basis, this fact is underrecognized, and thus, they are often regarded as dopamine unresponsive symptoms. However, substantial evidence indicates that many NMS respond to oral and transdermal dopaminergic therapies...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28805566/botulinum-toxin-therapy-for-nonmotor-aspects-of-parkinson-s-disease
#7
Jarosław Sławek, Mariusz Madaliński
The medical treatment of Parkinson's disease (PD) is symptomatic both in terms of motor and nonmotor aspects. The nonmotor symptoms therapy should be taken into account as many of them negatively influence the quality of life and are treatable. Botulinum neurotoxin (BoNT) offers effective treatment for drooling and bladder dysfunctions and alternative treatment for constipation and pain related to parkinsonism. BoNT for drooling is probably the best-documented therapy for nonmotor symptoms by clinical trials...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28805207/periodontal-diseases
#8
REVIEW
Denis F Kinane, Panagiota G Stathopoulou, Panos N Papapanou
Periodontal diseases comprise a wide range of inflammatory conditions that affect the supporting structures of the teeth (the gingiva, bone and periodontal ligament), which could lead to tooth loss and contribute to systemic inflammation. Chronic periodontitis predominantly affects adults, but aggressive periodontitis may occasionally occur in children. Periodontal disease initiation and propagation is through a dysbiosis of the commensal oral microbiota (dental plaque), which then interacts with the immune defences of the host, leading to inflammation and disease...
June 22, 2017: Nature Reviews. Disease Primers
https://www.readbyqxmd.com/read/28804939/assessing-the-application-of-knowledge-in-clinical-problem-solving-the-structured-professional-reasoning-exercise
#9
M P Escudier, M J Woolford, J A Tricio
INTRODUCTION: Clinical reasoning is a fundamental and core clinical competence of healthcare professionals. The study aimed to investigate the utility of the Structured Professional Reasoning Exercise (SPRE), a new competence assessment method designed to measure dental students' clinical reasoning in simulated scenarios, covering the clinical areas of Oral Disease, Primary Dental Care and Restorative Dentistry, Child Dental Health and Dental Practice and Clinical Governance. MATERIALS AND METHODS: A total of 313 year-5 students sat for the assessment...
August 14, 2017: European Journal of Dental Education: Official Journal of the Association for Dental Education in Europe
https://www.readbyqxmd.com/read/28804786/health-impact-assessment-of-the-uk-soft-drinks-industry-levy-a-comparative-risk-assessment-modelling-study
#10
Adam D M Briggs, Oliver T Mytton, Ariane Kehlbacher, Richard Tiffin, Ahmed Elhussein, Mike Rayner, Susan A Jebb, Tony Blakely, Peter Scarborough
BACKGROUND: In March, 2016, the UK Government proposed a tiered levy on sugar-sweetened beverages (SSBs; high tax for drinks with >8 g of sugar per 100 mL, moderate tax for 5-8 g, and no tax for <5 g). We estimate the effect of possible industry responses to the levy on obesity, diabetes, and dental caries. METHODS: We modelled three possible industry responses: reformulation to reduce sugar concentration, an increase of product price, and a change of the market share of high-sugar, mid-sugar, and low-sugar drinks...
January 2017: Lancet. Public Health
https://www.readbyqxmd.com/read/28804673/changing-trends-in-oral-cancer-a-global-scenario
#11
REVIEW
Neha Gupta, Ritu Gupta, Arun Kumar Acharya, Basavaraj Patthi, Venkatesh Goud, Somanath Reddy, Anshul Garg, Ashish Singla
Oral cancer is one of the highly prevalent cancers worldwide and a leading cause of mortality in certain regions like South-Central Asia. It is a major public health problem. Late diagnosis, high mortality rates and morbidity are characteristics of the disease worldwide. For control of oral cancer an idea of the coverage of the same in the various regions is necessary. The estimated incidence, mortality and 5-year survival due to lip, oral cavity cancer in world is 3, 00, 373(2.1%), 1, 45, 328(1.8%) and 7, 02, 149(2...
December 2016: Nepal journal of epidemiology
https://www.readbyqxmd.com/read/28804672/necessity-of-oral-health-intervention-in-schizophrenic-patients-a-review
#12
REVIEW
Swati Gupta, Pratibha Pk, Richa Gupta
Individuals with mental illness often cannot perform day to day activities due to a psychiatric or emotional disorder. Schizophrenia is one such psychiatric disorder characterized by worsening self-care ability with progressing mental illness. This disease may potentially deteriorate oral health by affecting the subject's ability to perform oral hygiene measures. Literature on oral disease manifestations in schizophrenia is limited. Lack of desire for oral health care as well as generally poor awareness of oral health issues in these patients, compounded further by side effects of medications, may complicate dental management in schizophrenic patients...
December 2016: Nepal journal of epidemiology
https://www.readbyqxmd.com/read/28804662/fungal-bezoar-a-rare-cause-of-ureteral-obstruction
#13
Nabil Zeineddine, Wissam Mansour, Sandy El Bitar, Marco Campitelli, Neville Mobarakai
A 52-year-old male, with diabetes mellitus and alcoholic liver disease, presented to the Emergency Room for right flank pain of 3 days' duration, associated with dysuria. Physical examination revealed right flank tenderness with fever and hypotension; laboratory findings showed acute kidney injury and large blood and leucocytes in the urine. A CT abdomen and pelvis showed hydronephrosis of the right collecting system of a horseshoe kidney with air and hyperdense debris in the renal pelvis. Patient was treated for multisensitive Proteus mirabilis emphysematous pyelonephritis, and a right nephrostomy tube was inserted...
2017: Case Reports in Infectious Diseases
https://www.readbyqxmd.com/read/28804660/large-granular-lymphocytic-leukemia-a-report-of-response-to-rituximab
#14
Uroosa Ibrahim, Sara Parylo, Shiksha Kedia, Shafinaz Hussein, Jean Paul Atallah
Large granular lymphocytic (LGL) leukemia is a rare form of low grade leukemia characterized by large cytotoxic T cells or natural killer cells on morphological examination. Immunosuppressive therapy is employed as first-line therapy. Treatment options in refractory cases include the anti-CD52 antibody alemtuzumab and purine analogues. We report a rare case that responded to the anti-CD20 monoclonal antibody rituximab. A 77-year-old female presented with complaints of fatigue, fever, and chills of 3 months' duration...
2017: Case Reports in Hematology
https://www.readbyqxmd.com/read/28804515/mmx-%C3%A2-technology-and-its-applications-in-gastrointestinal-diseases
#15
REVIEW
Silvia Nardelli, Laura Francesca Pisani, Gian Eugenio Tontini, Maurizio Vecchi, Luca Pastorelli
The Multimatrix(®) (MMX(®)) preparation MMX(®) is a recently obtained drug formulation developed to facilitate release of high concentrations of active drugs into the colon, with a homogeneous distribution along all colonic segments, particularly the most distal ones; the distal colonic tracts, indeed, are the most difficult to reach in significant amounts when a drug is given orally. The MMX(®) formulation is characterized by a lipophilic matrix dispersed in a hydrophilic structure. Indeed, in the last few years, MMX(®) technology has been widely used in the development of various drugs for the treatment of inflammatory and infectious gastrointestinal diseases localized in the colon...
July 2017: Therapeutic Advances in Gastroenterology
https://www.readbyqxmd.com/read/28803990/high-doses-of-baicalin-induces-kidney-injury-and-fibrosis-through-regulating-tgf-%C3%AE-smad-signaling-pathway
#16
Yi Cai, Wanqing Ma, Yichuan Xiao, Bo Wu, Xiaobing Li, Fengrong Liu, Jianhua Qiu, Genshui Zhang
Baicalin is a major flavonoid compound purified from Scutellariae radix, which has been described as an herb in the Chinese Pharmacopoeia. Previous studies have suggested baicalin possessed extensive anti-inflammatory, anti-cancer, anti-viral properties. However, up to known, there have been no reports of safety and toxicity in the rats following oral administration of baicalin. In this present study, we showed the first evidence that treatment of baicalin (400, 800 and 1600mg/kg/day) induced significantly kidney injury and fibrosis...
August 10, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28803880/vitamin-d-and-symptoms-of-depression-in-overweight-or-obese-adults-a-cross-sectional-study-and-randomized-placebo-controlled-trial
#17
Aya Mousa, Negar Naderpoor, Maximilian P J de Courten, Barbora de Courten
Recent evidence suggests that vitamin D deficiency may contribute to increased risk of depression. However, previous studies are limited by variability in participant characteristics including vitamin D deficiency status and presence of existing diseases, use of low doses of vitamin D supplementation for short durations, and use of co-interventions or psychotropic drugs. We examined whether 25-hydroxyvitamin D (25(OH)D) concentrations were associated with symptoms of depression, as well as whether vitamin D supplementation reduced symptoms of depression in overweight or obese and vitamin D-deficient, but otherwise healthy adults...
August 10, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28803510/epizootic-hemorrhagic-disease-virus-serotype-6-outbreak-in-israeli-cattle-in-2015
#18
Natalia Golender, Yevgeny Khinich, Anna Gorohov, Itzik Abramovitz, Velizar Bumbarov
In September 2015, a large outbreak caused by epizootic hemorrhagic disease virus (EHDV) was identified in Israeli dairy and beef farms. The main clinical signs were reduced milk production, weakness, drooling, lameness and recumbency, fever, slight erythema of nasal and oral mucosae, weight loss, and abortion. Dyspnea, cachexia, and death were observed less frequently. The clinical diagnosis was confirmed by ELISAs and EHDV-specific real-time reverse transcription PCR (RT-rtPCR), followed by conventional RT-PCR of the VP2 gene and sequence analysis...
August 1, 2017: Journal of Veterinary Diagnostic Investigation
https://www.readbyqxmd.com/read/28803392/attitudes-of-individuals-with-gaucher-disease-toward-substrate-reduction-therapies
#19
Victoria F Wagner, Hope Northrup, S Shahrukh Hashmi, Joanne M Nguyen, Mary Kay Koenig, Jessica M Davis
Type 1 Gaucher disease (GD) is the most common lysosomal storage disorder. Previously, treatment for GD was limited to intravenous enzyme replacement therapies (ERTs). More recently, oral substrate reduction therapies (SRTs) were approved for treatment of GD. Although both therapies alleviate disease symptoms, attitudes toward SRTs and patient perceptions of health while using SRT have not been well established. Electronic surveys were administered to adults with GD and asked about treatment history, attitudes toward SRTs, and perception of health while using SRTs as compared to ERTs, if applicable to the participant...
August 13, 2017: Journal of Genetic Counseling
https://www.readbyqxmd.com/read/28802900/adolescent-chronic-variable-social-stress-influences-exploratory-behavior-and-nicotine-responses-in-male-but-not-female-balb-cj-mice
#20
M J Caruso, D E Reiss, J I Caulfield, J L Thomas, A N Baker, S A Cavigelli, H M Kamens
Anxiety disorders and nicotine use are significant contributors to global morbidity and mortality as independent and comorbid diseases. Early-life stress, potentially via stress-induced hypothalamic-pituitary-adrenal axis (HPA) dysregulation, can exacerbate both. However, little is known about the factors that predispose individuals to the development of both anxiety disorders and nicotine use. Here, we examined the relationship between anxiety-like behaviors and nicotine responses following adolescent stress...
August 9, 2017: Brain Research Bulletin
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