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https://www.readbyqxmd.com/read/29138046/novel-cremochylomicrons-for-improved-oral-bioavailability-of-the-antineoplastic-phytomedicine-berberine-chloride-optimization-and-pharmacokinetics
#1
Manal A Elsheikh, Yosra S R Elnaggar, Dalia A Hamdy, Ossama Y Abdallah
Berberine chloride (BER) is an antineoplastic phytomedicine that combat non-Hodgkin lymphoma. BER suffers from low oral bioavailability due to P-glycoprotein efflux and first-pass metabolism. Lymphatic drug targeting recently gained a profound attention due to circumventing hepatic first-pass metabolism and targeting lymph diseases. Therefore, novel BER-loaded cremochylomicrons were elaborated to mitigate BER drawbacks and enhance its lymphatic targeting and bioavailability. Optimized cremochylomicron was prepared with 2...
November 11, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29137811/improving-the-safety-of-metal-based-drugs-by-tuning-their-metabolism-with-chemoprotective-agents
#2
Jürgen Gailer
Metal-based drugs remain a tiny minority of all drugs that are on the market. The success story of the quintessential metal-based drug cisplatin (CP), which is intravenously administered to 70% of all cancer patients, however, demonstrates the inherent potential of metal-based drugs. A distinct disadvantage of CP is the dose-limiting severe toxic-side effects that it exerts in patients. To better understand the biomolecular basis for its toxicity, we employed a metallomics method to observe all platinum metabolites that are formed in blood plasma...
November 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29132395/impaired-mitochondrial-calcium-uptake-caused-by-tacrolimus-underlies-beta-cell-failure
#3
Angela Lombardi, Bruno Trimarco, Guido Iaccarino, Gaetano Santulli
BACKGROUND: One of the most common side effects of the immunosuppressive drug tacrolimus (FK506) is the increased risk of new-onset diabetes mellitus. However, the molecular mechanisms underlying this association have not been fully clarified. METHODS: We studied the effects of the therapeutic dose of tacrolimus on mitochondrial fitness in beta-cells. RESULTS: We demonstrate that tacrolimus impairs glucose-stimulated insulin secretion (GSIS) in beta-cells through a previously unidentified mechanism...
November 13, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29129847/effects-of-ketoconazole-on-cyclophosphamide-metabolism-evaluation-of-cyp3a4-inhibition-effect-using-the-in-vitro-and-in-vivo-models
#4
Le Yang, Chenyang Yan, Feng Zhang, Bo Jiang, Shouhong Gao, Youtian Liang, Lifeng Huang, Wansheng Chen
Cyclophosphamide (CP) is widely used in anticancer therapy regimens and 2-dechloroethylcyclophosphamide (DECP) is its side-chain dechloroethylated metabolite. N-dechloroethylation of CP mediated by the enzyme CYP3A4 yields nephrotoxic and neurotoxic chloroacetaldehyde (CAA) in equimolar amount to DECP. This study aimed to evaluate the inhibitory effect of ketoconazole (KTZ) on CP metabolism through in vitro and in vivo drug-drug interaction (DDI) research. Long-term treatment of KTZ induces hepatic injury; thus single doses of KTZ at low, middle, and high levels (10, 20, and 40 mg/kg) were investigated for pharmacokinetic DDI with CP...
November 13, 2017: Experimental Animals
https://www.readbyqxmd.com/read/29129744/upregulation-of-aquaporin-3-expression-by-diterpenoids-in-euphorbia-pekinensis-is-associated-with-activation-of-the-nf-%C3%AE%C2%BAb-signaling-pathway-in-the-co-culture-system-of-ht-29-and-raw-264-7%C3%A2-cells
#5
Hongli Yu, Lian Liu, Kuilong Wang, Hao Wu, Wei Wang, Xingde Zhang, Guojing Cui, Xiaobing Cui, Jianyu Huang
This study was designed to evaluate the toxic effects of diterpenoids separated from the roots of Euphorbia pekinensis, a type of widely used traditional Chinese medicine. This herb has intestinal toxicity associated with its complex diterpenoids. In this study, the diterpenoids (pekinenin A, pekinenin C, pekinenin F, pekinenin G, yuexiandajisu A, (-)-(1S)-15-hydroxy-18-carboxycembrene) elevated the expression of interleukin 1 beta and tumor necrosis factor alpha in a dose-dependent manner at doses of 6.25, 12...
November 9, 2017: Biochimie
https://www.readbyqxmd.com/read/29127758/-physical-activity-the-holy-grail-of-modern-medicine
#6
Vladimír Tuka, Martina Daňková, Karel Riegel, Martin Matoulek
Movement is the basic attribute of life. It is not surprising that the return to regular physical activity is a very effective and cheap means of preventing and treating most non-cummunicable diseases. Therefore, every physician should be able to prescribe a suitable physical activity. The minimum amount of physical activity with proven effects in primary prevention of chronic diseases is relatively low: 150 minutes of moderate physical activity or 75 minutes of high intensity exercise per week or a combination of the two...
2017: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/29126698/hybrid-drug-combination-combination-of-ferulic-acid-and-metformin-as-anti-diabetic-therapy
#7
REVIEW
Rakesh Nankar, P K Prabhakar, Mukesh Doble
BACKGROUND AND PURPOSE: Ferulic acid, an anti-oxidant phytochemical present in several dietary components, is known to produce wide range of pharmacological effects. It is approved for use in food industry as a preservative and in sports food. Previous reports from our lab have shown synergistic interaction of ferulic acid with metformin in cell lines and diabetic rats. The purpose of this review is to compile information about anti-diabetic activity of ferulic acid in in vitro and in vivo models with special emphasis on activity of ferulic acid when combined with metformin...
October 24, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/29125183/ovarian-surgery-for-symptom-relief-in-women-with-polycystic-ovary-syndrome
#8
REVIEW
Sam Lepine, Junyoung Jo, Mostafa Metwally, Ying C Cheong
BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine condition, affecting approximately one in 10 women. PCOS is defined by two of three features: oligo- or anovulation, clinical or biochemical hyperandrogenism or both, or polycystic ovaries.Women with PCOS can have a wide range of health problems, including infrequent and irregular periods, unwanted hair growth and acne, and subnormal fertility. Long-term health concerns include an increased risk of heart disease, diabetes and the development of precancerous disease of the womb...
November 10, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/29124057/radiation-induced-cardiovascular-disease-a-clinical-perspective
#9
REVIEW
Syed Wamique Yusuf, Bhanu Prasad Venkatesulu, Lakshmi Shree Mahadevan, Sunil Krishnan
Cancer survival has improved dramatically, and this has led to the manifestation of late side effects of multimodality therapy. Radiation (RT) to the thoracic malignancies results in unintentional irradiation of the cardiac chambers. RT-induced microvascular ischemia leads to disruption of capillary endothelial framework, and injury to differentiated myocytes results in deposition of collagen and fibrosis. Coexistence of risk factors of metabolic syndrome and preexisting atherosclerosis in addition to RT exposure results in accelerated occurrence of major coronary events...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/29123929/palpitations-and-asthenia-associated-with-venlafaxine-in-a-cyp2d6-poor-metabolizer-and-cyp2c19-intermediate-metabolizer
#10
Sofia Garcia, Michael Schuh, Anvir Cheema, Herjot Atwal, Paldeep S Atwal
Cardiotoxicity has been extensively reported in venlafaxine (VEN) overdoses. Asthenia is also among the common side effects described for this antidepressant. VEN is metabolized mainly by CYP2D6 and to a minor extent by CYP2C19 to the major active metabolite O-desmethylvenlafaxine (ODV). Altered pharmacokinetic parameters in patients with polymorphisms in the CYP2D6 and CYP2C19 genes that result in decreased enzymatic activity have been documented. Here we describe a patient case of VEN associated palpitations and asthenia...
2017: Case Reports in Genetics
https://www.readbyqxmd.com/read/29123391/surface-enhanced-raman-scattering-investigation-of-targeted-delivery-and-controlled-release-of-gemcitabine
#11
Ty Santiago, Rebecca Sinnott DeVaux, Katarzyna Kurzatkowska, Ricardo Espinal, Jason I Herschkowitz, Maria Hepel
Advanced and metastatic cancer forms are extremely difficult to treat and require high doses of chemotherapeutics, inadvertently affecting also healthy cells. As a result, the observed survival rates are very low. For instance, gemcitabine (GEM), one of the most effective chemotherapeutic drugs used for the treatment of breast and pancreatic cancers, sees only a 20% efficacy in penetrating cancer tissue, resulting in <5% survival rate in pancreatic cancer. Here, we present a method for delivering the drug that offers mitigation of side effects, as well as a targeted delivery and controlled release of the drug, improving its overall efficacy...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/29122550/supply-and-demand-how-does-variation-in-atmospheric-oxygen-during-development-affect-insect-tracheal-and-mitochondrial-networks
#12
John M VandenBrooks, Gregory Gstrein, Jason Harmon, Jessica Friedman, Matthew Olsen, Anna Ward, Gregory Parker
Atmospheric oxygen is one of the most important atmospheric component for all terrestrial organisms. Variation in atmospheric oxygen has wide ranging effects on animal physiology, development, and evolution. This variation in oxygen has the potential to affect both respiratory systems (the supply side) and mitochondrial networks (the demand side) in animals. Insect respiratory systems supplying oxygen to tissues in the gas phase through blind ended tracheal systems are particularly susceptible to this variation...
November 6, 2017: Journal of Insect Physiology
https://www.readbyqxmd.com/read/29121886/the-strange-case-of-mr-h-starting-dialysis-at-90%C3%A2-years-of-age-clinical-choices-impact-on-ethical-decisions
#13
Giorgina Barbara Piccoli, Andreea Corina Sofronie, Jean-Philippe Coindre
BACKGROUND: Starting dialysis at an advanced age is a clinical challenge and an ethical dilemma. The advantages of starting dialysis at "extreme" ages are questionable as high dialysis-related morbidity induces a reflection on the cost- benefit ratio of this demanding and expensive treatment in a person that has a short life expectancy. Where clinical advantages are doubtful, ethical analysis can help us reach decisions and find adapted solutions. CASE PRESENTATION: Mr...
November 9, 2017: BMC Medical Ethics
https://www.readbyqxmd.com/read/29121830/acute-reversible-toxic-encephalopathy-during-capecitabine-and-oxaliplatin-treatment
#14
João Godinho, Mafalda Casa-Nova, Teresa Mesquita, Maria João Baptista, Francisco Araújo, José Vale, José Luís Passos Coelho
Introduction Capecitabine is a fluoropyrimidine commonly used in the treatment of colorectal cancer which may cause central nervous system toxicity, namely cerebellar dysfunction. Case report We describe a 77-year-old man undergoing adjuvant treatment of colon cancer with capecitabine and oxaliplatin who presented with acute cerebellar ataxia and encephalopathy that progressed to coma. Diagnosis of toxic encephalopathy was made after the exclusion of alternative causes of neurological dysfunction and complete resolution of clinical findings with permanent discontinuation of chemotherapy...
January 1, 2017: Journal of Oncology Pharmacy Practice
https://www.readbyqxmd.com/read/29120249/alcohol-addiction-the-safety-of-available-approved-treatment-options
#15
Mariangela Antonelli, Anna Ferrulli, Luisa Sestito, Gabriele A Vassallo, Claudia Tarli, Carolina Mosoni, Maria M Rando, Antonio Mirijello, Antonio Gasbarrini, Giovanni Addolorato
Alcohol Use Disorder (AUD) is a leading cause of mortality and morbidity worldwide. At present disulfiram, naltrexone and acamprosate are approved for the treatment of AUD in U.S. and Europe. Nalmefene is approved in Europe and sodium oxybate is approved in Italy and Austria only. Baclofen received a "temporary recommendation for use" in France. Areas covered. The safety of the medications mentioned above on liver, digestive system, kidney function, nervous system, pregnancy and lactation and their possible side effects are described and discussed...
November 9, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29119409/recent-developments-in-adc-technology-preclinical-studies-signal-future-clinical-trends
#16
REVIEW
Penelope M Drake, David Rabuka
The antibody-drug conjugate (ADC) field is in a transitional period. Older approaches to conjugate composition and dosing regimens still dominate the ADC clinical pipeline, but preclinical work is driving a rapid evolution in how we strategize to improve efficacy and reduce toxicity towards better therapeutic outcomes. These advances are largely based upon a body of investigational studies that together offer a deeper understanding of the absorption, distribution, metabolism, and excretion (ADME) and drug metabolism and pharmacokinetics (DMPK) fates of both the intact conjugate and its small-molecule component...
November 8, 2017: BioDrugs: Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy
https://www.readbyqxmd.com/read/29118925/bardoxolone-methyl-cddo-me-or-rta402-induces-cell-cycle-arrest-apoptosis-and-autophagy-via-pi3k-akt-mtor-and-p38-mapk-erk1-2-signaling-pathways-in-k562-cells
#17
Xin-Yu Wang, Xue-Hong Zhang, Li Peng, Zheng Liu, Yin-Xue Yang, Zhi-Xu He, Hong-Wan Dang, Shu-Feng Zhou
Chronic myeloid leukemia (CML) treatment remains a challenge due to drug resistance and severe side effect, rendering the need on the development of novel therapeutics. CDDO-Me (Bardoxolone methyl), a potent Nrf2 activator and NF-κB inhibitor, is a promising candidate for cancer treatment including leukemia. However, the underlying mechanism for CDDO-Me in CML treatment is unclear. This study aimed to evaluate the molecular interactome of CDDO-Me in K562 cells using the quantitative proteomics approach stable-isotope labeling by amino acids in cell culture (SILAC) and explore the underlying mechanisms using cell-based functional assays...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/29117660/nebivolol-induced-hyperkalemia-case-report
#18
Karmela Altabas, Velimir Altabas, Tonko Gulin
In this article, we document a conclusive case of nebivolol-induced hyperkalemia for the first time in the known medical literature. Hyperkalemia is associated with serious conditions such as cardiac arrhythmias and sudden cardiac death. Nebivolol was not known to cause hyperkalemia, and this event is not listed in its summary of product characteristics (SmPC). For older beta blockers, hyperkalemia is recognized as a rare adverse event linked to cytochrome P450 2D6 (CYP2D6) polymorphism and poor drug degradation...
December 2016: Acta Clinica Croatica
https://www.readbyqxmd.com/read/29117215/effects-of-root-pruning-on-the-physicochemical-properties-and-microbial-activities-of-poplar-rhizosphere-soil
#19
Da-Wei Jing, Fang-Chun Liu, Ming-You Wang, Hai-Lin Ma, Zhen-Yu Du, Bing-Yao Ma, Yu-Feng Dong
This study aimed to determine the effects of root pruning on the physicochemical characteristics and microbial activities of poplar rhizosphere soil. The root systems of 5-year-old poplar (Populus×euramericana cv. 'Neva') trees were manually pruned at 6, 8, or 10 times diameter at breast height (DBH) from the trunk (severe, moderate, and light, respectively) along both inter-row sides. Moderate root pruning significantly increased the concentrations of amino acids, organic acids, and total sugars in the root exudates and decreased the pH of rhizosphere soil...
2017: PloS One
https://www.readbyqxmd.com/read/29115594/pentoxifylline-exerts-anti-inflammatory-effects-on-cerebral-ischemia-reperfusion%C3%A2-induced-injury-in-a-rat-model-via-the-p38-mitogen-activated-protein-kinase-signaling-pathway
#20
Jianqing Dong, Xinmei Yuan, Weiwei Xie
Pentoxifylline exhibits complex functions with extensive pharmacological effects and is used therapeutically due to its therapeutic effects and rapid metabolism in the body, with no cumulative effects and few side effects. The present study investigated the effects of pentoxifylline on cerebral ischemia reperfusion‑induced injury (IRI) through suppression of inflammation in rats. Hematoxylin and eosin staining was performed to evaluate the number of neurocytes, and ELISAs were applied to measure tumor necrosis factor‑α, interleukin‑6, malondialdehyde and superoxide dismutase activities...
November 3, 2017: Molecular Medicine Reports
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