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https://www.readbyqxmd.com/read/28057543/high-throughput-lipolysis-in-96-well-plates-for-rapid-screening-of-lipid-based-drug-delivery-systems
#1
M D Mosgaard, P J Sassene, H Mu, T Rades, A Müllertz
The high-throughput in vitro intestinal lipolysis model (HTP) applicable for rapid and low scale screening of lipid based drug delivery systems (LbDDS) was optimized and adjusted as to be conducted in 96-well plates (HTP-96). Three different LbDDS (I-III) loaded with danazol or cinnarizine where used as model systems. The distributions of cinnarizine and danazol in the aqueous and precipitated digestion phases generated during lipolysis in the HTP-96 were compared with previously published data obtained from the HTP...
January 2, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28017149/htlv-1-associated-neurological-disorders
#2
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-and-experimental-models-of-the-gastrointestinal-environment-2-phase-behavior-and-drug-solubilisation-capacity-of-a-type-i-lipid-based-drug-formulation-after-digestion
#3
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 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 gastrointestinal microenvironment containing a digested triglyceride-based (Type I) drug formulation...
December 12, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27934534/partitioning-into-colloidal-structures-of-fasted-state-intestinal-fluid-studied-by-molecular-dynamics-simulations
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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)...
November 7, 2016: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/27626530/danazol-treatment-for-telomere-diseases
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27607446/allogeneic-hematopoietic-stem-cell-transplantation-for-dyskeratosis-congenita
#13
Shaimaa Elmahadi, Hideki Muramatsu, Seiji Kojima
PURPOSE OF REVIEW: Dyskeratosis congenita is an inherited bone marrow failure syndrome caused by defects in telomere maintenance. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for bone marrow failure because of dyskeratosis congenita. The present review summarizes the literature with respect to the diagnosis and treatment of patients with dyskeratosis congenita who received HSCT, and discusses the recent progress in the management of dyskeratosis congenita...
November 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/27599419/danazol-induced-peliosis-hepatis-accompanied-by-disseminated-intravascular-coagulation-in-a-patient-with-myelodysplastic-syndrome-transformed-from-aplastic-anemia
#14
Yasuhiro Tsukamoto, Junichi Kiyasu, Hayato Utsunomiya, Yasuhiro Nakashima, Ilseung Choi, Youko Suehiro, Yoshifusa Aratake, Yasunobu Abe
Peliosis hepatis (PH) is a condition involving benign tumors pathologically characterized by multiple blood-filled cavities, mostly affecting the liver and spleen. Androgenic-steroids are widely used in patients with bone marrow failure syndromes (e.g.: aplastic anemia) and these patients are at increased risk of developing PH. Although patients with PH are generally asymptomatic, PH can progress to liver failure and even fatal spontaneous intraabdominal hemorrhage. Therefore, early diagnosis is critical in order to prevent life-threatening complications of PH...
August 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27533712/in-vivo-precipitation-of-poorly-soluble-drugs-from-lipid-based-drug-delivery-systems
#15
P J Sassene, M H Michaelsen, M D Mosgaard, M K Jensen, E Van Den Broek, K M Wasan, H Mu, T Rades, A Müllertz
Precipitation of poorly water-soluble drugs from lipid-based drug delivery systems (LbDDS) has been studied extensively during in vitro lipolysis but has never been shown in vivo. The aim of this study was therefore to investigate if drug precipitation can occur from LbDDS during transit of the gastrointestinal tract in vivo. Rats were administered 300 μL of either of two LbDDS (LbDDS I and LbDDS II) loaded with danazol or fenofibrate (or paracetamol to assess gastric emptying). The rats were euthanized at various time points after administration of both LbDDS containing either drug, and the contents of the stomach and proximal part of the small intestine were harvested...
October 3, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27503693/hormonal-therapy-for-endometriosis-from-molecular-research-to-bedside
#16
Claudia Tosti, Antonella Biscione, Giuseppe Morgante, Giuseppe Bifulco, Stefano Luisi, Felice Petraglia
Endometriotic lesions are associated with hormonal imbalance, including increased estrogen synthesis, metabolism and progesterone resistance. These hormonal changes cause increased proliferation, inflammation, pain and infertility. Hormonal imbalances are targets for treatment. Therapeutic strategies and innovations of hormonal drugs for endometriosis are increasing. Acting on estrogen receptors are hormonal drugs decreasing systemic and local estrogen synthesis (GnRH analogs, GnRH antagonists, Aromatase inhibitors) or estrogen activity (selective estrogen receptor modulators)...
May 27, 2016: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://www.readbyqxmd.com/read/27488902/studying-the-propensity-of-compounds-to-supersaturate-a-practical-and-broadly-applicable-approach
#17
Henrik Palmelund, Cecilie Maria Madsen, Jakob Plum, Anette Müllertz, Thomas Rades
Supersaturating drug delivery systems can enhance the oral bioavailability of poorly soluble drug compounds. Supersaturation of such compounds has been studied in many different ways; however, a more standardized method is required. The rationale of choosing suitable concentrations of supersaturation to study has previously been very inconsistent. This makes comparisons between studies and compounds difficult, as the propensity of compounds to supersaturate varies greatly. This study presents a standardized method to study the supersaturation of drug compounds...
October 2016: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27394004/analysis-of-sulfate-metabolites-of-the-doping-agents-oxandrolone-and-danazol-using-high-performance-liquid-chromatography-coupled-to-tandem-mass-spectrometry
#18
S Rzeppa, L Viet
The direct detection of sulfate conjugates of anabolic androgenic steroids (AAS) can be a powerful tool in doping control analysis. By skipping the solvolysis step analysis time can be reduced, and due to long term sulfate metabolites the detection time can be significantly extended as demonstrated for some AAS. This study presents the successful identification of sulfate metabolites of the doping agents oxandrolone and danazol in excretion urines by high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS)...
September 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/27379972/adenomyosis-a-systematic-review-of-medical-treatment
#19
A Pontis, M N D'Alterio, S Pirarba, C de Angelis, R Tinelli, S Angioni
Adenomyosis is a heterogeneous gynaecologic condition with a range of clinical presentations, the most common being heavy menstrual bleeding and dysmenorrhoea; however, patients can also be asymptomatic. Several studies support the theory that adenomyosis results from invasion of the endometrium into the myometrium, causing alterations in the junctional zone. These changes are commonly seen on imaging studies, such as transvaginal ultrasound and magnetic resonance imaging. The aim of this review is to discuss the medical approach to the management of adenomyosis symptoms, including pain and abnormal uterine bleeding...
September 2016: Gynecological Endocrinology
https://www.readbyqxmd.com/read/27364943/thyroid-hormones-and-complement-parameters-in-hereditary-angioedema-with-c1-inhibitor-deficiency
#20
Ibolya Czaller, Dorottya Csuka, Zsuzsanna Zotter, Nóra Veszeli, Edit Takács, Éva Imreh, Lilian Varga, Henriette Farkas
BACKGROUND: Thyroid hormones control and up-regulate the synthesis of many plasma proteins. OBJECTIVE: To explore possible associations between thyroid hormone and complement levels in patients with hereditary angioedema resulting from the deficiency of the C1-inhibitor (C1-INH-HAE). METHODS: In this case-control study, serum thyrotropin, free triiodothyronine (FT3), and free thyroxine (FT4) levels, anti-thyroid peroxidase and antithyroglobulin antibody titers, and C1-INH concentrations were measured in 117 euthyroid patients with C1-INH-HAE and compared with their clinical properties...
August 2016: Annals of Allergy, Asthma & Immunology
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