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https://www.readbyqxmd.com/read/28505451/toward-successful-cyclodextrin-based-solubility-enabling-formulations-for-oral-delivery-of-lipophilic-drugs-solubility-permeability-tradeoff-biorelevant-dissolution-and-the-unstirred-water-layer
#1
Noa Fine-Shamir, Avital Beig, Moran Zur, David Lindley, Jon Miller, Arik Dahan
The purpose of this work was to investigate key factors dictating the success/failure of cyclodextrin-based solubility-enabling formulations for oral delivery of low-solubility drugs. We have studied the solubility, the permeability, and the solubility-permeability interplay, of the highly lipophilic drug danazol, formulated with different levels (8.5, 10, 20 and 30%) of the commonly used hydroxypropyl-β-cyclodextrin (HPβCD), accounting for the biorelevant solubilization of the drug along the gastrointestinal tract (GIT), the unstirred water layer (UWL) adjacent to the GI membrane, and the overall absorption...
May 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28465239/solution-or-suspension-does-it-matter-for-lipid-based-systems-in-vivo-studies-of-chase-dosing-lipid-vehicles-with-aqueous-suspensions-of-a-poorly-soluble-drug
#2
A T Larsen, R Holm, A Müllertz
In this study, the potential of co-administering an aqueous suspension with a placebo lipid vehicle, i.e. chase dosing, was investigated in rats relative to the aqueous suspension alone or a solution of the drug in the lipid vehicle. The lipid investigated in the present study was Labrafil M2125CS and three evaluated poorly soluble model compounds, danazol, cinnarizine and halofantrine. For cinnarizine and danazol the oral bioavailability in rats after chase dosing or dosing the compound dissolved in Labrafil M21515CS was similar and significantly higher than for the aqueous suspension...
April 29, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28337228/evaluation-of-efficacy-and-safety-of-dan-e-fukang-soft-extract-in-the-treatment-of-endometriosis-a-meta-analysis-of-39-randomized-controlled-trials-enrolling-5442-patients
#3
REVIEW
Yantao Li, Te Li, Shilin Song
Objective. To systematically evaluate the efficacy and safety of Dan'e-fukang soft extract in endometriosis treatment. Method. PubMed, CNKI, Wanfang Database, VIP, SinoMed, and Cochrane Library were searched. Randomized controlled trials (RCTs) comparing the efficacy of Dan'e-fukang soft extract and conventional western medicines for endometriosis treatment were included. The data were extracted independently by two people and analyzed using RevMan 5.2.0 software. The relative risk (RR) and mean difference (MD) with 95% confidence intervals were considered as effective outcome indicators...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28293407/thrombocytopenia-in-patients-with-chronic-hepatitis-c-virus-infection
#4
REVIEW
Sumit Dahal, Smrity Upadhyay, Rashmi Banjade, Prajwal Dhakal, Nabin Khanal, Vijaya Raj Bhatt
Thrombocytopenia in patients with chronic hepatitis C virus (HCV) infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia in different measures. The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although at present, it is possible to avoid this challenge with the use of the sole Direct Antiviral Agents (DAAs) as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28237650/inhibition-and-inactivation-of-human-cyp2j2-implications-in-cardiac-pathophysiology-and-opportunities-in-cancer-therapy
#5
REVIEW
Aneesh Karkhanis, Yanjun Hong, Eric Chun Yong Chan
Extrahepatic cytochrome P450 enzymes (CYP450) are pivotal in the metabolism of endogenous substrates and xenobiotics. CYP2J2 is a major cardiac CYP450 and primarily metabolizes polyunsaturated fatty acids such as arachidonic acid to cardioactive epoxyeicosatrienoic acids. Due to its role in endobiotic metabolism, CYP2J2 has been actively studied in recent years with the focus on its biological functions in cardiac pathophysiology. Additionally, CYP2J2 metabolizes a number of xenobiotics such as astemizole and terfenadine and is potently inhibited by danazol and telmisartan...
February 23, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28188718/-hematopoietic-stem-cells-transplant-in-patients-with-common-variable-immunodeficiency-is-a-therapeutic-option
#6
Julio César Cambray-Gutiérrez, Diana Andrea Herrera-Sánchez, Patricia López-Pérez, Aurora Chávez-García, Marco Antonio Yamazaki-Nakashimada
BACKGROUND: Patients with common variable immunodeficiency show higher incidence of sinopulmonary and gastrointestinal infections, as well as lymphoproliferative and autoimmune diseases. The treatment of choice is replacement therapy with human gamma-globulin. Hematopoietic stem cell transplantation is a non-conventional therapeutic modality. CASE REPORT: Twenty-six-year old woman with no family or hereditary history of primary immune deficiencies or consanguinity, with repeated episodes of otitis, sinusitis, gastroenteritis and bronchitis since childhood...
January 2017: Revista Alergia Mexico: Organo Oficial de la Sociedad Mexicana de Alergia e Inmunología, A.C
https://www.readbyqxmd.com/read/28154580/systemic-inflammatory-response-and-severe-thrombocytopenia-after-endovascular-thoracic-aortic-aneurysm-repair
#7
Valentina Silvestrin, Stefano Bonvini, Michele Antonello, Franco Grego, Roberto Vettor, Marco Rossato
After Endovascular repair of thoracic aortic aneurysm, a systemic inflammatory response, named postimplantation syndrome, can develop. This syndrome is characterized by fever, leukocytosis, and elevated CRP plasma levels and its pathogenetic mechanisms are still unknown. Although this syndrome generally resolves within few days, some patients develop a persisting severe inflammatory reaction leading to mild or severe complications. Here we describe the case of a male patient who developed postimplantation inflammatory syndrome and severe thrombocytopenia after endovascular repair of thoracic aortic aneurysm...
2017: Case Reports in Medicine
https://www.readbyqxmd.com/read/28123991/enhanced-bioavailability-of-danazol-nanosuspensions-by-wet-milling-and-high-pressure-homogenization
#8
Naveen Kanthamneni, Satyanarayana Valiveti, Mita Patel, Heather Xia, Yin-Chao Tseng
INTRODUCTION: The majority of drugs obtained through synthesis and development show poor aqueous solubility and dissolution velocity, resulting in reduced bioavailability of drugs. Most of these problems arise from formulation-related performance issues, and an efficient way to overcome these obstacles and to increase dissolution velocity is to reduce the particle size of drug substances to form drug nanosuspensions. MATERIALS AND METHODS: Danazol nanosuspensions were prepared by wet milling (WM) and high-pressure homogenization (HPH) methods...
October 2016: International Journal of Pharmaceutical Investigation
https://www.readbyqxmd.com/read/28057543/high-throughput-lipolysis-in-96-well-plates-for-rapid-screening-of-lipid-based-drug-delivery-systems
#9
Mette D Mosgaard, Philip J Sassene, Huiling Mu, Thomas Rades, Anette Müllertz
The high-throughput in vitro intestinal lipolysis model (HTP) applicable for rapid and low-scale screening of lipid-based drug delivery systems (LbDDSs) was optimized and adjusted as to be conducted in 96-well plates (HTP-96). Three different LbDDSs (I-III) loaded with danazol or cinnarizine were used as model systems. The distributions of cinnarizine and danazol in the aqueous and precipitated digestion phases generated during lipolysis in HTP-96 were compared with previously published data obtained from HTP...
January 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28017149/htlv-1-associated-neurological-disorders
#10
Muhammad Yasir Khan, Ishaq Nasib Khan, Muhammad Farman, Saleh Al Karim, Ishtiaq Qadri, Muhammad Amjad Kamal, Khalid Al Ghamdi, Steve Harakeh
Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus which is endemic to certain regions of the world and infects around 10-20 million people. HTLV-1 is the etiologic agent of Adult T cell leukemia/lymphoma and HTLV-1 associated neurological disorders including mainly HTLV-1 associated myelopathy/Tropical spastic paraparesis. The involvement of the central nervous diseases occurs among: HTLV-1 infected patients from endemic areas, HIV positive individuals and drug users. The ability of HTLV-1 to cause associated neuropathies starts with the virus crossing the blood brain barrier (BBB), then entering and infecting the cells of the central nervous system...
December 22, 2016: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/27936778/computational-models-of-the-gastrointestinal-environment-2-phase-behavior-and-drug-solubilization-capacity-of-a-type-i-lipid-based-drug-formulation-after-digestion
#11
Woldeamanuel A Birru, Dallas B Warren, Sifei Han, Hassan Benameur, Christopher J H Porter, Colin W Pouton, David K Chalmers
Lipid-based drug formulations can greatly enhance the bioavailability of poorly water-soluble drugs. Following the oral administration of formulations containing tri- or diglycerides, the digestive processes occurring within the gastrointestinal (GI) tract hydrolyze the glycerides to mixtures of free fatty acids and monoglycerides that are, in turn, solubilized by bile. The behavior of drugs within the resulting colloidal mixtures is currently not well characterized. This work presents matched in vitro experimental and molecular dynamics (MD) theoretical models of the GI microenvironment containing a digested triglyceride-based (Type I) drug formulation...
February 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27934534/partitioning-into-colloidal-structures-of-fasted-state-intestinal-fluid-studied-by-molecular-dynamics-simulations
#12
Michael Holmboe, Per Larsson, Jamshed Anwar, Christel A S Bergström
We performed molecular dynamics (MD) simulations to obtain insights into the structure and molecular interactions of colloidal structures present in fasted state intestinal fluid. Drug partitioning and interaction were studied with a mixed system of the bile salt taurocholate (TCH) and 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLiPC). Spontaneous aggregation of TCH and DLiPC from unconstrained MD simulations at the united-atom level using the Berger/Gromos54A7 force fields demonstrated that intermolecular hydrogen bonding between TCH molecules was an important factor in determining the overall TCH and DLiPC configuration...
December 6, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/27933735/danazol-has-potential-to-cause-pkc-translocation-cell-cycle-dysregulation-and-apoptosis-in-breast-cancer-cells
#13
Suman Jyoti Deka, Ashalata Roy, Vibin Ramakrishnan, Debasis Manna, Vishal Trivedi
Danazol, the established clinical drug, has given promising therapeutic results in a series of clinical trials with breast cancer patients. Danazol shares structural similarities with several known PKC agonists and fits well into the C1 domain. Danazol binds to the C1b domain of PKC with Kd of 5.64 ± 1.27 μm. MD simulation studies further support that the PKC-danazol molecular model is stable and showing minimum distortion to the structure during the simulation period. Immunofluorescence and Western blotting studies indicate that MDAMB-231 cells stimulated with danazol exhibit translocation of PKCα to the plasma membrane...
December 9, 2016: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/27913466/nontransplant-therapy-for-bone-marrow-failure
#14
Danielle M Townsley, Thomas Winkler
Nontransplant therapeutic options for acquired and constitutional aplastic anemia have significantly expanded during the last 5 years. In the future, transplant may be required less frequently. That trilineage hematologic responses could be achieved with the single agent eltrombopag in refractory aplastic anemia promotes new interest in growth factors after years of failed trials using other growth factor agents. Preliminary results adding eltrombopag to immunosuppressive therapy are promising, but long-term follow-up data evaluating clonal evolution rates are required before promoting its standard use in treatment-naive disease...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27905115/treatment-for-hereditary-angioedema-with-normal-c1-inh-and-specific-mutations-in-the-f12-gene-hae-fxii
#15
K Bork, K Wulff, G Witzke, J Hardt
Hereditary angioedema with normal C1 esterase inhibitor and mutations in the F12 gene (HAE-FXII) is associated with skin swellings, abdominal pain attacks, and the risk of asphyxiation due to upper airway obstruction. It occurs nearly exclusively in women. We report our experience treating HAE-FXII with discontinuation of potential trigger factors and drug therapies. The study included 72 patients with HAE-FXII. Potential triggers included estrogen-containing oral contraceptives (eOC), hormonal replacement therapy, or angiotensin-converting enzyme inhibitors...
November 6, 2016: Allergy
https://www.readbyqxmd.com/read/27864873/hereditary-haemorrhagic-telangiectasia-to-transplant-or-not-to-transplant-is-there-a-right-time-for-liver-transplantation
#16
Yannick D Muller, Roland Oppliger, Romain Breguet, Philippe Meyer, Laura Rubbia-Brandt, Pierre-Auguste Petignat, Thomas Harr, Eric Dayer, Jörg D Seebach
BACKGROUND & AIMS: Hereditary haemorrhagic telangiectasia is characterized by arterio-venous malformations (AVM). It frequently involves the liver without clinical symptoms, but may lead to biliary ischaemia, portal hypertension, or fatal high-output heart failure. The indication of liver transplantation is controversial. METHODS: Herein, we report the case of a 65-year-old female patient with a 'double Osler syndrome' consisting of hereditary haemorrhagic telangiectasia (HHT) and type I hereditary angioedema diagnosed at the age of 25 and 22 years respectively...
December 2016: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/27774820/myelofibrosis-an-update-on-drug-therapy-in-2016
#17
REVIEW
Prithviraj Bose, Srdan Verstovsek
Primary myelofibrosis (PMF) is the least common but the most aggressive of the classic Philadelphia chromosome-negative myeloproliferative neoplasms. Survival is much shorter in PMF than in polycythemia vera (PV) or essential thrombocythemia (ET). Post-PV/ET myelofibrosis (MF) is clinically indistinguishable from PMF and approached similarly. Areas covered: Current pharmacologic therapy of MF revolves around the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib, which dramatically improves constitutional symptoms and splenomegaly in the majority of patients, and improves overall survival (OS)...
December 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27626530/danazol-treatment-for-telomere-diseases
#18
LETTER
Stéphane Jouneau, Mallorie Kerjouan, Charles Ricordel
No abstract text is available yet for this article.
September 15, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27626529/danazol-treatment-for-telomere-diseases
#19
LETTER
Mathis Grossmann
No abstract text is available yet for this article.
September 15, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27626528/danazol-treatment-for-telomere-diseases
#20
LETTER
Danielle M Townsley, Bogdan Dumitriu, Neal S Young
No abstract text is available yet for this article.
September 15, 2016: New England Journal of Medicine
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