1,419,629 results match your criteria Drugs & aging[Journal]


A Bufadienolide-Enriched Fraction of Bryophyllum pinnatum Inhibits Human Myometrial Contractility In Vitro.

Planta Med 2018 Dec 18. Epub 2018 Dec 18.

Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland.

has been used since the 1970s to prevent premature labour, first in anthroposophic hospitals and, more recently, also in the main Swiss perinatal centres. However, it is not known which compounds in leaves contribute to the tocolytic effect. Here we studied the effects of a flavonoid-enriched fraction, the corresponding flavonoid aglycon mixture, a bufadienolide-enriched fraction, and leaf press juice on human myometrial contractility . Read More

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http://dx.doi.org/10.1055/a-0810-7704DOI Listing
December 2018

An Update on Addison's Disease.

Exp Clin Endocrinol Diabetes 2018 Dec 18. Epub 2018 Dec 18.

Department of Medicine III, University Hospital Carl Gustav Carus, Dresden, Germany.

Addison's disease - the traditional term for primary adrenal insufficiency (PAI) - is defined as the clinical manifestation of chronic glucocorticoid- and/or mineralocorticoid deficiency due to failure of the adrenal cortex which may result in an adrenal crisis with potentially life-threatening consequences. Even though efficient and safe pharmaceutical preparations for the substitution of endogenous gluco- and mineralocorticoids are established in therapy, the mortality in patients with PAI is still increased and the health-related quality of life (HRQoL) is often reduced.PAI is a rare disease but recent data report an increasing prevalence. Read More

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http://dx.doi.org/10.1055/a-0804-2715DOI Listing
December 2018

[A case of gout secondary to primary myelofibrosis].

Beijing Da Xue Xue Bao Yi Xue Ban 2018 Dec;50(6):1117-1119

Department of Rheumatology and Immunology,Peking University First Hospital, Beijing 100034, China.

A 52-year-old man was referred to our department with a 2-year history of polyarthritis. He was diagnosed as gout due to acute arthritis of bilateral feet dorsum 2 years ago,but he didn't receive any standard treatment. 1 year ago,there were more and more joints evolved during the gout attack, and many subcutaneous nodules occurred. Read More

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December 2018

[Progressive pseudorheumatoid dysplasia misdiagnosed as ankylosing spondylitis: a case report].

Beijing Da Xue Xue Bao Yi Xue Ban 2018 Dec;50(6):1112-1116

Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191, China.

In this study, we reported a case of progressive pseudorheumatoid dysplasia in Peking University Third Hospital. A 56-year-old male patient presented with hip joint pain for more than 40 years and multiple joints pain with limitation of movements of these joints for 28 years. This patient suffered from joint pain and impaired range of motion of the hip, knee, elbow and shoulder gradually, associated with difficulty in walking and inability to take care of himself. Read More

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December 2018

[Posterior reversible encephalopathy syndrome in systemic lupus erythematosus: a case report].

Beijing Da Xue Xue Bao Yi Xue Ban 2018 Dec;50(6):1102-1107

Department of Rheumatology and Immunology, Peking University First Hospital, Beijing 100034, China.

This case report concerns a 22-year-old woman who had been diagnosed with systemic lupus erythematosus (SLE). She had intermittent fever, butterfly erythema, photosensitivity, oral ulcers, and multiple arthralgia in the past seven years, but she did not adhere to regular treatments. The edema of the lower extremities and face aggravated in the recent two weeks, so she was admitted to our Department of Rheumatology and Clinical Immunology. Read More

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December 2018

[Preparation and evaluation of blank and doxorubicin loaded poly (acrylic acid) microspheres for embolization].

Beijing Da Xue Xue Bao Yi Xue Ban 2018 Dec;50(6):1070-1077

The State Key Laboratory of Natural and Biomimetic Drugs, Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.

Objective: To prepare ion exchange doxorubicin-loaded poly (acrylic acid) microspheres (DPMs) and evaluate the properties of these chemoembolic agents.

Methods: Poly (acrylic acid) microspheres (PMs) without drug were prepared by inverse suspension polymerization method and then doxorubicin was loaded by ion exchange mechanism to prepare DPMs. Optical microscope was used to investigate the morphology and particle size distribution of PMs and DPMs; fluorescence microscope and confocal microscope were used to observe the distribution of doxorubicin after drug loading. Read More

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December 2018

[A multi-center cross-sectional survey of medicine application in patients with osteoarthritis in China].

Beijing Da Xue Xue Bao Yi Xue Ban 2018 Dec;50(6):1044-1048

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing 100044, China.

Objective: To investigate the clinical characteristics, the medicine application and to evaluate the disease activity in patients with osteoarthritis (OA) in China.

Methods: This was a cross-sectional study. Totally 1 066 cases of OA from 40 hospitals in China from April to October 2017 were retrospectively enrolled. Read More

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December 2018

[Clinical characteristic of 74 cases of malignant tumor in rheumatoid arthritis].

Beijing Da Xue Xue Bao Yi Xue Ban 2018 Dec;50(6):986-990

Department of Rheumatology and Immunology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China.

Objective: To investigate the clinical characteristics of rheumatoid arthritis (RA) patients with malignant tumor.

Methods: Retrospective summary was made of 1 562 in patients of RA from January 2011 to June 2017. In the study, 74 RA patients with malignant tumor were reviewed and analyzed, and the general conditions, tumor types, RA and tumor onset sequence, and the medication situation were analyzed. Read More

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December 2018

[Value of serum matrix metalloproteinase 3 in the assessment of early rheumatoid arthritis].

Beijing Da Xue Xue Bao Yi Xue Ban 2018 Dec;50(6):981-985

Department of Rheumatology and Immunology, Peking University People's Hospital & Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135) Beijing 100044, China; State Key Laboratory of Natural and Biomimetic Drugs, Peking University School of Pharmaceutical Sciences, Beijing 100191, China.

Objective: To investigate the expression level of serum matrix metalloproteinase 3 (MMP3) in early rheumatoid arthritis (ERA) patients with normal C-reaction protein (CRP) or erythrocyte sedimentation rate (ESR), and the significance in disease assessment.

Methods: In the study, 133 cases of early RA patients, 25 osteoarthritis (OA) patients and 60 healthy controls in Peking University People's Hospital from 2011 to 2015 were included. The RA patients were further divided into 4 groups according to levels of CRP and ESR: 88 patients with increased CRP and increased ESR, 15 patients with normal CRP and normal ESR, 17 patients with normal CRP but increased ESR, and 13 patients with increased CRP but normal ESR. Read More

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December 2018

[Diagnosis and treatment of antiphospholipid antibody-related recurrent spontaneous abortion and analysis of therapeutic drugs and pregnancy outcome in 75 patients with antiphospholipid syndrome].

Beijing Da Xue Xue Bao Yi Xue Ban 2018 Dec;50(6):956-961

Department of Rheumatology and Immunology, Peking University Third Hospital, Beijing 100191, China.

Recurrent spontaneous abortion is one of the common complications in women of childbearing age during pregnancy. The immune factor accounts for a large proportion of many causes. Antiphospholipid antibody syndrome is the most common type of acquired thrombophilia disease. Read More

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December 2018

Study on Therapeutic Action and Mechanism of TMZ Combined with RITA Against Glioblastoma.

Cell Physiol Biochem 2018 Dec 11;51(6):2536-2546. Epub 2018 Dec 11.

Background/aims: Glioblastoma multiforme (GBM) is a malignant and aggressive central nervous system (CNS) tumor with high mortality and low survival rate. Effective treatment of GMB is a challenge worldwide. Temozolomide (TMZ) is a drug used to treat GBM, while the survival period of GBM patients with positive treatment remains less than 15 months. Read More

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http://dx.doi.org/10.1159/000495923DOI Listing
December 2018

Characterization of a DNA Aptamer for Ovarian Cancer Clinical Tissue Recognition and in Vivo Imaging.

Cell Physiol Biochem 2018 Dec 11;51(6):2564-2574. Epub 2018 Dec 11.

Xiangya Hospital, Central South University, Changsha,

Backgrounds/aims: Ovarian cancer is the most lethal gynaecologic malignancy and is difficult to detect early. The inefficient early diagnosis of ovarian cancer is the main contributor to its high mortality rate. Aptamers, as chemical antibodies, are single-stranded DNA or RNA oligonucleotides that target cells or molecules with high affinity. Read More

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http://dx.doi.org/10.1159/000495925DOI Listing
December 2018

Effect of Ionic Strength, pH and Chemical Displacers on the Percentage Protein Binding of Protein-Bound Uremic Toxins.

Blood Purif 2018 Dec 18:1-10. Epub 2018 Dec 18.

Background And Objectives: While trying to optimize the dialysis clearances of protein-bound uremic toxins (PBUTs), their percentage protein binding (% PB) is an important parameter. We evaluated the effects of ionic strength, pH change and chemical displacers on the dissociation of PBUTs from albumin in vitro.

Methods: PBUTs, such as 3-Carboxy-4-methyl-5-propyl-2-furan-propanoic acid (CMPF), p-cresylsulfate (PCS), indoxyl sulfate (IS) and indole-3-acetic acid (IAA), were spiked with human serum albumin (HSA) solution prepared with different Nacl concentrations and pH values or in the presence of a series of chemical displacers. Read More

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http://dx.doi.org/10.1159/000495343DOI Listing
December 2018

The FOXK1-CCDC43 Axis Promotes the Invasion and Metastasis of Colorectal Cancer Cells.

Cell Physiol Biochem 2018 Dec 11;51(6):2547-2563. Epub 2018 Dec 11.

Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou,

Background/aims: The CCDC43 gene is conserved in human, rhesus monkey, mouse and zebrafish. Bioinformatics studies have demonstrated the abnormal expression of CCDC43 gene in colorectal cancer (CRC). However, the role and molecular mechanism of CCDC43 in CRC remain unknown. Read More

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http://dx.doi.org/10.1159/000495924DOI Listing
December 2018

Targeting PPARα for the Treatment and Understanding of Cardiovascular Diseases.

Cell Physiol Biochem 2018 Dec 12;51(6):2760-2775. Epub 2018 Dec 12.

Department of Nephrology, Children's Hospital of Nanjing Medical University, Nanjing, China.

Three members of the peroxisome proliferator-activated receptor (PPAR) family, PPARα, PPARγ, and PPARβ/δ, have been investigated widely over the past few decades. Although the roles of these PPARs and their agonists/antagonists were defined in clinical and basic studies, the conflicting results from these studies indicate that more analysis is needed to understand the roles of PPARs. PPARα is a ligand-activated transcription factor that contributes to the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. Read More

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http://dx.doi.org/10.1159/000495969DOI Listing
December 2018

Immobilization of type I collagen/hyaluronic acid multilayer coating on enoxacin loaded titania nanotubes for improved osteogenesis and osseointegration in ovariectomized rats.

Colloids Surf B Biointerfaces 2018 Dec 13;175:409-420. Epub 2018 Dec 13.

Department of Bone and Joint Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, PR China. Electronic address:

Titania nanotubes (Ti-NTs) have been proven to be good drug carriers and can release drugs efficiently around implants. Enoxacin (EN) is a broad-spectrum antibiotic that has the ability of anti-osteoclastogenesis. Immobilization of extracellular matrix components on the surface of the material can greatly enhance the biological activity of the implant and slow down the release rate of the drug in Ti-NTs. Read More

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http://dx.doi.org/10.1016/j.colsurfb.2018.12.033DOI Listing
December 2018

Discovery of new potent hits against intracellular Trypanosoma cruzi by QSAR-based virtual screening.

Eur J Med Chem 2018 Nov 29;163:649-659. Epub 2018 Nov 29.

LabMol - Laboratory for Molecular Modeling and Drug Design, Faculdade de Farmacia, Universidade Federal de Goiás - UFG, Rua 240, Qd.87, Goiania, GO, 74605-510, Brazil. Electronic address:

Chagas disease is a neglected tropical disease (NTD) caused by the protozoan parasite Trypanosoma cruzi and is primarily transmitted to humans by the feces of infected Triatominae insects during their blood meal. The disease affects 6-8 million people, mostly in Latin America countries, and kills more people in the region each year than any other parasite-born disease, including malaria. Moreover, patient numbers are currently increasing in non-endemic, developed countries, such as Australia, Japan, Canada, and the United States. Read More

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http://dx.doi.org/10.1016/j.ejmech.2018.11.062DOI Listing
November 2018

Addressing the nexus of risk: Biobehavioral outcomes from a cluster randomized trial of the Women's Health CoOp Plus in Pretoria, South Africa.

Drug Alcohol Depend 2018 Dec 3;195:16-26. Epub 2018 Dec 3.

Research Computing Division, RTI International, 3040 E. Cornwallis Road, Research Triangle Park, NC, USA.

Background: HIV prevalence has increased among South African women who use alcohol and other drugs (AOD). However, HIV prevention and treatment efforts have not focused on this population. This study presents the efficacy of the Women's Health CoOp Plus (WHC+) in a cluster-randomized trial to reduce AOD use, gender-based violence, and sexual risk and to increase linkage to HIV care among women who use AODs, compared with HIV counseling and testing alone. Read More

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http://dx.doi.org/10.1016/j.drugalcdep.2018.10.036DOI Listing
December 2018

Immunosuppression of Syrian golden hamsters accelerates relapse but not the emergence of resistance in Leishmania infantum following recurrent miltefosine pressure.

Int J Parasitol Drugs Drug Resist 2018 Dec 11;9:1-7. Epub 2018 Dec 11.

Laboratory of Microbiology, Parasitology and Hygiene (LMPH), University of Antwerp, Antwerp, Belgium. Electronic address:

Although miltefosine (MIL) has only been approved for the treatment of visceral leishmaniasis (VL) in 2002, its application in monotherapy already led to the development of two confirmed MIL-resistant isolates by 2009. Although liposomal amphotericin B is recommended as first-line treatment in Europe, MIL is still occasionally used in HIV co-infected patients. Since their immune system is incapable of controlling the infection, high parasite burdens and post-treatment relapses are common. Read More

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http://dx.doi.org/10.1016/j.ijpddr.2018.12.001DOI Listing
December 2018

Analysis of tolerance to antidepressant drug treatment in FDA Adverse Event Reporting System.

Pharmacol Res 2018 Dec 15. Epub 2018 Dec 15.

Psychiatry Unit, Department of Biomedical and Clinical Sciences, ASST Fatebenefratelli-Sacco University Hospital, Università di Milano, Milan, Italy.

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http://dx.doi.org/10.1016/j.phrs.2018.12.013DOI Listing
December 2018

Reply to Dr. Gentili' "Analysis of tolerance to antidepressant drugs in FDA Adverse Event Reporting System".

Authors:
Michele Fornaro

Pharmacol Res 2018 Dec 15. Epub 2018 Dec 15.

Department of Psychiatry, Federico II University of Naples, 80131, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.phrs.2018.12.012DOI Listing
December 2018

Differential effects of protein kinase C-eta on apoptosis versus senescence.

Cell Signal 2018 Dec 15. Epub 2018 Dec 15.

Department of Microbiology, Immunology & Genetics, University of North Texas Health Science Center, Fort Worth, TX, USA.

Protein kinase C-eta (PKCη) is considered an anti-apoptotic kinase, which promotes cell survival and chemoresistance in several cancers, including breast cancer. We have recently shown that PKCη positively regulates the anti-apoptotic protein Mcl-1 in breast cancer cells, and depletion of PKCη induced proteasomal degradation of Mcl-1. We therefore examined if depletion of PKCη would enhance cellular sensitivity to chemotherapeutic agents. Read More

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http://dx.doi.org/10.1016/j.cellsig.2018.12.003DOI Listing
December 2018

A novel amphipathic cell-penetrating peptide based on the N-terminal glycosaminoglycan binding region of human apolipoprotein E.

Biochim Biophys Acta Biomembr 2018 Dec 15. Epub 2018 Dec 15.

Department of Biophysical Chemistry, Kyoto Pharmaceutical University, 5 Misasagi-Nakauchi-cho, Yamashina-ku, Kyoto 607-8414, Japan. Electronic address:

In the direct cell membrane penetration, arginine-rich cell-penetrating peptides are thought to penetrate into cells across the hydrophobic lipid membranes. To investigate the effect of the amphipathic property of arginine-rich peptide on the cell-penetrating ability, we designed a novel amphipathic cell-penetrating peptide, A2-17, and its derivative, A2-17KR, in which all lysine residues are substituted with arginine residues, based on the glycosaminoglycan binding region in the N-terminal α-helix bundle of human apolipoprotein E. Isothermal titration calorimetry showed that A2-17 variants have a strong ability to bind to heparin with high affinity. Read More

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http://dx.doi.org/10.1016/j.bbamem.2018.12.010DOI Listing
December 2018

Does the intake of ethanol affect oral absorption of poorly soluble drugs?

J Pharm Sci 2018 Dec 15. Epub 2018 Dec 15.

Department of Pharmacy, Uppsala University, BMC P.O. Box 580, SE-751 23 Uppsala, Sweden.

The presence of ethanol in gastrointestinal (GI) fluids may increase the solubility of poorly water-soluble drugs. This suggests that intake of ethanol with such compounds could result in increased drug absorption in the stomach and/or duodenum because of the greater concentration gradient present. To test this hypothesis, in vitro dissolution of two poorly soluble compounds (indomethacin and felodipine) was studied in simulated GI rat fluids in the presence or absence of ethanol. Read More

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http://dx.doi.org/10.1016/j.xphs.2018.12.006DOI Listing
December 2018

Monocyte phagocytosis of malaria β-haematin in the presence of artemisinin, amodiaquine, chloroquine, doxycycline, primaquine, pyrimethamine and quinine.

Exp Parasitol 2018 Dec 15. Epub 2018 Dec 15.

Department of Biochemistry, School of Biochemistry, Genetics and Microbiology, University of KwaZulu-Natal, Pietermaritzburg Campus, Private Bag X01, Scottsville, 3209, South Africa. Electronic address:

The intraerythrocytic malaria parasite digests haemoglobin to provide amino acids for metabolism and releases toxic haem that is sequestered into haemozoin, a non-toxic, insoluble, crystalline pigment. Following erythrocyte rupture, haemozoin is released into circulation and phagocytosed by monocytes. Phagocytosed haemozoin and antimalarial drugs have both been reported to modulate monocyte functions. Read More

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http://dx.doi.org/10.1016/j.exppara.2018.12.002DOI Listing
December 2018

Anti-tumour necrosis factor biological therapies for the treatment of uveitic macular oedema (UMO) for non-infectious uveitis.

Cochrane Database Syst Rev 2018 Dec 18;12:CD012577. Epub 2018 Dec 18.

Academic Unit of Ophthalmology, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK, B15 2TT.

Background: Non-infectious uveitis describes a heterogenous group of ocular disorders characterised by intraocular inflammation in the absence of infection. Uveitis is a leading cause of visual loss, most commonly due to uveitic macular oedema (UMO). Treatment is aimed at reducing disease activity by suppression of the intraocular inflammatory response. Read More

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http://dx.doi.org/10.1002/14651858.CD012577.pub2DOI Listing
December 2018

Accelerating Drug Development in Pediatric Oncology With the Clinical Pharmacology Storehouse.

J Clin Pharmacol 2018 Dec 18. Epub 2018 Dec 18.

Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, IL, USA.

Pediatric drug development is a challenging process due to the rarity of the population, the need to meet regulatory requirements across the globe, the associated uncertainty in extrapolating data from adults, the paucity of validated biomarkers, and the lack of systematic testing of drugs in pediatric patients. In oncology, pediatric drug development has additional challenges that have historically delayed availability of safe and effective medicines for children. In particular, the traditional approach to pediatric oncology drug development involves conducting phase 1 studies in children once the drug has been characterized and in some cases approved for use in adults. Read More

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http://dx.doi.org/10.1002/jcph.1359DOI Listing
December 2018

Current and future priorities for the development of optimal HIV drugs.

Curr Opin HIV AIDS 2018 Dec 17. Epub 2018 Dec 17.

Department of HIV and Global Hepatitis Programme, World Health Organization, Geneva, Switzerland.

Purpose Of Review: To summarize global efforts to accelerate access to simpler, safer and more affordable antiretroviral drugs and how this has shaped HIV treatment policy over the last decade, and outline future priorities. Several expert consultations aimed at aligning opportunities for optimization of antiretroviral drugs have been convened by WHO in partnership with academic institutions, international agencies, innovators and manufacturers. The increased access to lifelong treatment for people living with HIV also brings about new challenges in the long-term use of antiretrovirals (ARVs). Read More

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http://dx.doi.org/10.1097/COH.0000000000000527DOI Listing
December 2018

RNA Interference-Based Cancer Drugs: The Roadblocks, and the "Delivery" of the Promise.

Nucleic Acid Ther 2018 Dec 18. Epub 2018 Dec 18.

Division of Pharmacoengineering and Molecular Pharmaceutics, Center for Nanotechnology in Drug Delivery, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.

Nucleic acid-based therapeutics like synthetic small interfering RNAs have been exploited to modulate gene function, taking advantage of RNA interference (RNAi), an evolutionally conserved biological process. Recently, the world's first RNAi drug was approved for a rare genetic disorder in the liver. However, there are significant challenges that need to be resolved before RNAi can be translated in other genetic diseases like cancer. Read More

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http://dx.doi.org/10.1089/nat.2018.0762DOI Listing
December 2018

A new rice-derived short peptide potently alleviated hyperuricemia induced by potassium oxonate in rats.

J Agric Food Chem 2018 Dec 18. Epub 2018 Dec 18.

Gout that caused by hyperuricemia affects human health seriously and more efficient drugs are urgently required clinically. In this study, a novel peptide named RDP1 (AAAAGAKAR, 785.91 Da) was identified from the extract of shelled fruits of Oryza Sativa. Read More

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http://dx.doi.org/10.1021/acs.jafc.8b05879DOI Listing
December 2018

Building Functional Nanodevices with Vesicle-Templated Porous Polymer Nanocapsules.

Acc Chem Res 2018 Dec 18. Epub 2018 Dec 18.

Department of Chemistry , University of Connecticut , 55 North Eagleville Road , Storrs , Connecticut 06269-3060 , United States.

Vesicle-templated nanocapsules offer a unique combination of properties enabled by robust shells with single-nanometer thickness containing programmed uniform pores capable of fast and selective mass transfer. These capsules emerged as a versatile platform for creating functional devices, such as nanoreactors, nanosensors, and containers for the delivery of drugs and imaging agents. Nanocapsules are synthesized by a directed assembly method using self-assembled bilayers of vesicles as temporary scaffolds. Read More

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http://dx.doi.org/10.1021/acs.accounts.8b00442DOI Listing
December 2018

Generating and working with Drosophila cell cultures: Current challenges and opportunities.

Wiley Interdiscip Rev Dev Biol 2018 Dec 18:e339. Epub 2018 Dec 18.

Department of Biology, Drosophila Genomics Resource Center, Indiana University Bloomington, Bloomington, Indiana.

The use of Drosophila cell cultures has positively impacted both fundamental and biomedical research. The most widely used cell lines: Schneider, Kc, the CNS and imaginal disc lines continue to be the choice for many applications. Drosophila cell lines provide a homogenous source of cells suitable for biochemical experimentations, transcriptomics, functional genomics, and biomedical applications. Read More

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http://dx.doi.org/10.1002/wdev.339DOI Listing
December 2018

Gene Silencing with siRNA (RNA Interference): A New Therapeutic Option during Ex-vivo Machine Liver Perfusion Preservation.

Liver Transpl 2018 Dec 18. Epub 2018 Dec 18.

Department of Surgery, Division of Organ Transplantation, UMass Memorial Medical Center, University of Massachusetts, Worcester, MA.

RNA interference (RNAi) is a natural process of post-transcriptional gene regulation that has raised a lot of attention culminating with the Nobel prize in Medicine in 2006. RNAi-based therapeutics have been tested in experimental transplantation to reduce ischemia reperfusion injury (IRI) with success. Modulation of genes of the innate immune system, as well as apoptotic genes, and those involved in the NF-κB pathways can reduce liver injury in rodent liver pedicle clamping and transplantation models of IRI. Read More

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http://dx.doi.org/10.1002/lt.25383DOI Listing
December 2018

Differentiation of Aneugens and Clastogens in the In Vitro Micronucleus Test by Kinetochore Scoring Using Automated Image Analysis.

Environ Mol Mutagen 2018 Dec 18. Epub 2018 Dec 18.

Bayer AG, Investigational Toxicology, Berlin, Germany.

The in vitro micronucleus test according to OECD Test Guideline 487 (TG 487) is widely used to investigate the genotoxic potential of drugs. Besides the identification of in vitro genotoxicants, the assay can be complemented with kinetochore staining for the differentiation between clastogens and aneugens. This differentiation constitutes a major contribution to risk assessment as especially aneugens show a threshold response. Read More

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http://dx.doi.org/10.1002/em.22259DOI Listing
December 2018

[Medical aspects on sauna bathing].

Authors:
Bertil Olsson

Lakartidningen 2018 Dec 18;115. Epub 2018 Dec 18.

Lunds Universitet - Dept of Cardiology Lund, Sweden Lunds Universitet - Dept of Cardiology Lund, Sweden.

The literature describing medical aspects on sauna bathing is briefly reviewed. The circulatory effects of heating and subsequent cooling related to sauna bath differ with age, underlying medical condition and use of drugs. The circulatory changes may often be beneficial but can sometimes prove dangerous. Read More

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December 2018

Risk of tuberculosis in patients with immune-mediated diseases on biological therapies: a population-based study in a tuberculosis endemic region.

Rheumatology (Oxford) 2018 Dec 14. Epub 2018 Dec 14.

Institute of Digestive Disease, Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.

Objectives: Real-world epidemiological data on the risk of tuberculosis (TB) in patients with immune-mediated diseases treated with biologics are scarce in TB endemic areas. We investigated the incidence of TB in a population-based setting and stratified the risk of TB among different biological therapies.

Methods: We collected medical data from a territory-wide computerized database in Hong Kong. Read More

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http://dx.doi.org/10.1093/rheumatology/key364DOI Listing
December 2018

Evaluation of possible proarrhythmic potency: comparison of the effect of dofetilide, cisapride, sotalol, terfenadine and verapamil on hERG and native IKr currents and on cardiac action potential.

Toxicol Sci 2018 Dec 18. Epub 2018 Dec 18.

Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Szeged, Hungary.

Introduction: The proarrhythmic potency of drugs is usually attributed to the IKr current block. During safety pharmacology testing analysis of IKr in cardiomyocytes was replaced by hERG test using automated patch-clamp systems in stable transfected cell lines. Aim of the present study was to compare the effect of proarrhythmic compounds on hERG and IKr currents and on cardiac action potential. Read More

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http://dx.doi.org/10.1093/toxsci/kfy299DOI Listing
December 2018

Seamless Designs: Current Practice and Considerations for Early-Phase Drug Development in Oncology.

J Natl Cancer Inst 2018 Dec 17. Epub 2018 Dec 17.

Biostatistics and Bioinformatics, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins, Baltimore, MD.

Traditionally, drug development has evaluated dose, safety, activity, and comparative benefit in a sequence of phases using trial designs and endpoints specifically devised for each phase. Innovations in drug development seek to consolidate the phases and rapidly expand accrual with "seamless" trial designs. Although consolidation and rapid accrual may yield efficiencies, widespread use of seamless first-in-human (FiH) trials without careful consideration of objectives, statistical analysis plans, or trial oversight raises concerns. Read More

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http://dx.doi.org/10.1093/jnci/djy196DOI Listing
December 2018

Systematic review and network meta-analysis Medical therapies to prevent recurrence of post-operative Crohn's disease.

J Crohns Colitis 2018 Dec 14. Epub 2018 Dec 14.

Department of Gastroenterology, Tallaght Hospital, Tallaght, Dublin 24, Ireland.

Background And Aims: Surgery is an important treatment for Crohn's disease (CD) but recurrence occurs in up to 80% of individuals post-operatively. The efficacy of several drugs to prevent post-operative recurrence has been studied in previous meta-analyses, but a number of randomised controlled trials (RCTs) have recently been published. We therefore performed an updated systematic review and network meta-analysis to investigate this issue. Read More

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http://dx.doi.org/10.1093/ecco-jcc/jjy216DOI Listing
December 2018

Minimum inhibitory concentrations of fluoroquinolones and pyrazinamide susceptibility correlate to clinical improvement in MDR-TB patients - a nationwide Swedish cohort study over two decades.

Clin Infect Dis 2018 Dec 18. Epub 2018 Dec 18.

Division of Infectious Diseases, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.

Introduction: Minimum inhibitory concentration (MIC) testing, unlike routine drug susceptibility testing (DST) at a single critical concentration, quantifies drug resistance. The association of MICs and treatment outcome in multidrug-resistant tuberculosis (MDR-TB) patients is unclear. Therefore, we correlated MICs of first-and second-line TB drugs with time to sputum culture conversion (tSCC) and treatment outcome in MDR-TB patients. Read More

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http://dx.doi.org/10.1093/cid/ciy1068DOI Listing
December 2018

NeoDTI: neural integration of neighbor information from a heterogeneous network for discovering new drug-target interactions.

Bioinformatics 2019 Jan;35(1):104-111

Institute for Interdisciplinary Information Sciences, Tsinghua University, Beijing, China.

Motivation: Accurately predicting drug-target interactions (DTIs) in silico can guide the drug discovery process and thus facilitate drug development. Computational approaches for DTI prediction that adopt the systems biology perspective generally exploit the rationale that the properties of drugs and targets can be characterized by their functional roles in biological networks.

Results: Inspired by recent advance of information passing and aggregation techniques that generalize the convolution neural networks to mine large-scale graph data and greatly improve the performance of many network-related prediction tasks, we develop a new nonlinear end-to-end learning model, called NeoDTI, that integrates diverse information from heterogeneous network data and automatically learns topology-preserving representations of drugs and targets to facilitate DTI prediction. Read More

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http://dx.doi.org/10.1093/bioinformatics/bty543DOI Listing
January 2019

Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis.

JAMA 2018 Dec;320(23):2448-2460

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Ontario, Canada.

Importance: Harms and benefits of opioids for chronic noncancer pain remain unclear.

Objective: To systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain.

Data Sources And Study Selection: The databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control. Read More

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http://dx.doi.org/10.1001/jama.2018.18472DOI Listing
December 2018

Advanced gastric cancer: the value of systemic and intraperitoneal chemotherapy.

Acta Biomed 2018 Dec 17;89(8-S):104-109. Epub 2018 Dec 17.

Emergency, General and Trauma Surgery dept., Bufalini hospital, Cesena, Italy.

Several possibilities in treating advanced gastric cancer exist. Radical surgery associated with chemotherapy represents the cornerstone. Which one is more effective among neoadjuvant, adjuvant or perioperative chemotherapy is still a matter of debate. Read More

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December 2018

Hemolytic uremic syndrome: differential diagnosis with the onset of inflammatory bowel diseases.

Acta Biomed 2018 Dec 17;89(9-S):153-157. Epub 2018 Dec 17.

Pediatric Emergency Unit, University Hospital of Parma, Maternal and Infant Department, Parma, Italy.

Background: Shiga-toxin Escherichia coli productor (STEC) provokes frequently an important intestinal damage that may be considered in differential diagnosis with the onset of Inflammatory Bowel Disease (IBD). The aim of this work is to review in the current literature about Hemolytic Uremic Syndrome (HUS) and IBD symptoms at the onset, comparing the clinical presentation and symptoms, as the timing of diagnosis and of the correct treatment of both these conditions is a fundamental prognostic factor. A focus is made about the association between typical or atypical HUS and IBD and a possible renal involvement in patient with IBD (IgA-nephropathy). Read More

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December 2018

Predicting tumour response to anti-PD-1 immunotherapy with computational modelling.

Phys Med Biol 2018 Dec 18. Epub 2018 Dec 18.

7033 Wisconsin Institute for Medical Research Department of Medical Physics, University of Wisconsin at Madison, Madison, Wisconsin, UNITED STATES.

Cancer immunotherapy is a rapidly developing field, with numerous drugs and therapy combinations waiting to be tested in pre-clinical and clinical settings. However, the costly and time-consuming trial-and-error approach to development of new treatment paradigms creates a research bottleneck, motivating the development of complementary approaches. Computational modelling is a compelling candidate for this task, however, difficulties associated with the validation of such models limits their use in pre-clinical and clinical settings. Read More

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http://dx.doi.org/10.1088/1361-6560/aaf96cDOI Listing
December 2018

Recruiting potent membrane penetrability in tumor cell-targeted protein-only nanoparticles.

Nanotechnology 2018 Dec 18. Epub 2018 Dec 18.

Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Cataluña, SPAIN.

The membrane pore-forming activities of the antimicrobial peptide GWH1 have been evaluated in combination with the CXCR4-binding properties of the peptide T22, in self-assembling protein nanoparticles with high clinical potential. The resulting constructs, of 25 nm in size, show a dramatically improved cell penetrability into CXCR4+ cells (more than 10-fold) and enhanced endosomal escape (the lysosomal degradation dropping from 90 % to 50 %), when compared with equivalent protein nanoparticles lacking GWH1. These data reveal that GWH1 retains its potent membrane activity in form of nanostructured protein complexes. Read More

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http://dx.doi.org/10.1088/1361-6528/aaf959DOI Listing
December 2018
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Burdens of Invasive Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus Disease, Minnesota, USA.

Emerg Infect Dis 2019 Jan;25(1):171-174

During August 1, 2014-July 31, 2015, in 2 counties in Minnesota, USA, incidence of invasive methicillin-susceptible Staphylococcus aureus (MSSA) (27.1 cases/100,000 persons) was twice that of invasive methicillin-resistant S. aureus (13. Read More

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http://dx.doi.org/10.3201/eid2501.181146DOI Listing
January 2019
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