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clinical therapeutics

Rory J McCrimmon
Despite the introduction of newer technologies and improved insulin formulations, recurrent hypoglycaemia continues to affect the lives of many people with Type 1 and Type 2 diabetes. Developing strategies or therapies designed to prevent or minimize hypoglycaemia risk is of utmost importance to help individuals safely achieve glycaemic targets. Novel, educational or behavioural approaches need to be based on a clear understanding of the mechanisms underpinning both the detection of hypoglycaemia and why repeated exposure to hypoglycaemia leads to the development of a clinical syndrome referred to as impaired awareness of hypoglycaemia...
October 22, 2016: Diabetic Medicine: a Journal of the British Diabetic Association
Megan O'Reilly, Bernard Thébaud
Preterm birth occurs in approximately 11 % of all births worldwide. Advances in perinatal care have enabled the survival of preterm infants born as early as 23-24 weeks of gestation. However, many are affected by bronchopulmonary dysplasia (BPD)-a common respiratory complication of preterm birth, which has life-long consequences for lung health. Currently, there is no specific treatment for BPD. Recent advances in stem cell research have opened new therapeutic avenues for prevention/repair of lung damage...
October 22, 2016: Cell and Tissue Research
Lauren E Marshall, Roy Koomullil, Andra R Frost, Joel L Berry
A preclinical testing model for cancer therapeutics that replicates in vivo physiology is needed to accurately describe drug delivery and efficacy prior to clinical trials. To develop an in vitro model of breast cancer that mimics in vivo drug/nutrient delivery as well as physiological size and bio-composition, it is essential to describe the mass transport quantitatively. The objective of the present study was to develop in vitro and computational models to measure mass transport from a perfusion system into a 3D extracellular matrix (ECM)...
October 21, 2016: Annals of Biomedical Engineering
Walter Pirker, Regina Katzenschlager
Human gait depends on a complex interplay of major parts of the nervous, musculoskeletal and cardiorespiratory systems. The individual gait pattern is influenced by age, personality, mood and sociocultural factors. The preferred walking speed in older adults is a sensitive marker of general health and survival. Safe walking requires intact cognition and executive control. Gait disorders lead to a loss of personal freedom, falls and injuries and result in a marked reduction in the quality of life. Acute onset of a gait disorder may indicate a cerebrovascular or other acute lesion in the nervous system but also systemic diseases or adverse effects of medication, in particular polypharmacy including sedatives...
October 21, 2016: Wiener Klinische Wochenschrift
Jennifer C Cook, Richard H Tran, J Herbert Patterson, Jo E Rodgers
PURPOSE: The pharmacology, clinical efficacy, and safety profiles of evolving therapies for the management of chronic heart failure (HF) and acute decompensated heart failure (ADHF) are described. SUMMARY: HF confers a significant financial burden despite the widespread use of traditional guideline-directed medical therapies such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, and aldosterone receptor antagonists, and the rates of HF-related mortality and hospitalization have remained unacceptably high...
November 1, 2016: American Journal of Health-system Pharmacy: AJHP
Amirabbas Azizi, Robab Aboutorabi, Zahra Mazloum-Khorasani, Monavar Afzal-Aghaea, Hamed Tabesh, Mahmood Tara
BACKGROUND: There are 4 main types of chronic or noncommunicable diseases. Of these, diabetes is one of the major therapeutic concerns globally. Moreover, Iran is among the countries with the highest incidence of diabetic patients. Furthermore, library-based studies by researchers have shown that thus far no study has been carried out to evaluate the relationship between Web-based diabetic personal health records (DPHR) and self-care indicators in Iran. OBJECTIVE: The objective of this study is to examine the effect of Web-based DPHR on self-care status of diabetic patients in an intervention group as compared with a control group...
October 21, 2016: JMIR Medical Informatics
Tianfang Jiang, Qian Sun, Shengdi Chen
Oxidative stress reflects an imbalance between the overproduction and incorporation of free radicals and the dynamic ability of a biosystem to detoxify reactive intermediates. Free radicals produced by oxidative stress are one of the common features in several experimental models of diseases. Free radicals affect both the structure and function of neural cells, and contribute to a wide range of neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. Although the precise mechanisms that result in the degeneration of neurons and the relevant pathological changes remain unclear, the crucial role of oxidative stress in the pathogenesis of neurodegenerative diseases is associated with several proteins (such as α-synuclein, DJ-1, Amyloid β and tau protein) and some signaling pathways (such as extracellular regulated protein kinases, phosphoinositide 3-kinase/Protein Kinase B pathway and extracellular signal-regulated kinases 1/2) that are tightly associated with the neural damage...
October 18, 2016: Progress in Neurobiology
Kazuo Saito, Hitoshi Kihara
STUDY DESIGN: A randomized clinical trial, with patients treated either by new 2-step orthosis or by the figure-eight-type orthosis with the distal interphalangeal (DIP) joint extended. PURPOSE OF THE STUDY: To report on our new orthosis and to evaluate the treatment efficacy of using a 2-step orthosis for the treatment of a mallet finger of tendinous origin compared with a conventional orthosis. METHODS: Forty-four patients were randomized into the 2-step or conventional orthosis groups...
October 18, 2016: Journal of Hand Therapy: Official Journal of the American Society of Hand Therapists
Chao-Ming Hung, Ying-Chao Lin, Liang-Chih Liu, Sheng-Chu Kuo, Chi-Tang Ho, Tzong-Der Way
CWF-145, a synthetic 2-phenyl-4-quinolone derivative exerted potent cytotoxicity against prostate cancer. CWF-145 inhibited prostate cancer cell lines PC-3, DU-145 and LNCap. It had a very low IC50 about 200 nM against castrate-resistant prostate cancer (CRPC) PC-3. We found that CWF-145 had a similar effect to clinical trial antimitotic agents in cancer cells and normal cells. CWF-145 arrested cell cycle at G2/M phase by binding to the β-tubulin at the colchicine-binding site then disrupted microtubule polymerization...
October 18, 2016: Chemico-biological Interactions
Franziska Hopfner, Dietrich Haubenberger, Wendy R Galpern, Katrina Gwinn, Ashlee Van't Veer, Samantha White, Kailash Bhatia, Charles H Adler, David Eidelberg, William Ondo, Glenn T Stebbins, Caroline M Tanner, Rick C Helmich, Fred A Lenz, Roy V Sillitoe, David Vaillancourt, Jerrold L Vitek, Elan D Louis, Holly A Shill, Matthew P Frosch, Tatiana Foroud, Gregor Kuhlenbäumer, Andrew Singleton, Claudia M Testa, Mark Hallett, Rodger Elble, Günther Deuschl
Essential tremor (ET) is a common cause of significant disability, but its etiologies and pathogenesis are poorly understood. Research has been hampered by the variable definition of ET and by non-standardized research approaches. The National Institute of Neurological Disorders and Stroke (USA) invited experts in ET and related fields to discuss current knowledge, controversies, and gaps in our understanding of ET and to develop recommendations for future research. Discussion focused on phenomenology and phenotypes, therapies and clinical trials, pathophysiology, pathology, and genetics...
October 4, 2016: Parkinsonism & related Disorders
Yujin Myung, Heeyeon Kwon, Changsik Pak, Hobin Lee, Jae Hoon Jeong, Chan Yeong Heo
BACKGROUND: Breast augmentation with fat transfer does not bear the risks associated with silicone implantation. The method can potentially be especially useful in Asian women, who often reject augmentation mammoplasty with implants. This prospective clinical trial evaluated the effects of external breast expansion on breast density and vessel count using magnetic resonance imaging. METHODS: Thirty-four enrolled patients were instructed to apply one of two devices, the conventional BRAVA device (used in the AESTES trial) or a novel external expansion device (EVERA) designed for Asian women, continuously for 8 h per day for 12 weeks...
September 28, 2016: Journal of Plastic, Reconstructive & Aesthetic Surgery: JPRAS
F Heran Dreyfus, O Galatoire, P Koskas, F Lafitte, E Nau, O Bergès
Orbito-palpebral vascular pathology represents 10% of all the diseases of this area. The lesion may be discovered during a brain CT scan or MRI, or because it causes clinical symptoms such as orbital mass, visual or oculomotor alteration, pain, proptosis, or acute bleeding due to a complication of the lesion (hemorrhage, thrombosis). We present these lesions using an anatomical, clinical, imaging and therapeutic approach. We distinguish four different entities. Vascular tumors have common imaging characteristics (hypersignal on T2 sequence, contrast enhancement, abnormal vascularization well depicted with ultrasound and Doppler, and possible bleeding)...
October 18, 2016: Journal Français D'ophtalmologie
Man Chu, Lai Shan Tam, Jing Zhu, Delong Jiao, De Hua Liu, Zhe Cai, Jie Dong, Christopher Wei Kai Lam, Chun Kwok Wong
The newly named interleukin (IL)-36 subfamily member IL-38 has been shown to exert anti-inflammatory activity. However, the in vivo immunomodulatory activity of IL-38 was poorly investigated in systemic lupus erythematosus (SLE). We have investigated the expression of CD4(+)IL-17(+) Th17, CD4(+)IFN-γ(+) Th1 and CD3(+)CD4(-)CD8(-) double negative (DN) T cells and the related immunopathological mechanisms in female MRL/lpr mice model of spontaneous lupus-like disease, with or without IL-38 treatment. Intravenous administration of murine recombinant IL-38 into MRL/lpr mice can ameliorate the lupus-like clinical symptoms including proteinuria, leukocyteuria and skin lesions...
October 17, 2016: Immunobiology
Wylie S Palmer
The entry of small molecule inhibitors of the bromodomain and extra C-terminal domain (BET) family of bromodomains into the clinic has demonstrated the therapeutic potential for this class of epigenetic acetyl-lysine reader proteins. Within the past two years, the development of potent inhibitors for the bromodomain and PHD finger containing protein (BRPF) family and the tripartite motif containing protein 24 (TRIM24) have been reported and are the subject of this review. Both proteins contain other domains with diverse functions and can also be part of a complex of proteins which have implications in epigenetic signaling and disease...
March 2016: Drug Discovery Today. Technologies
Guillaume Andrieu, Anna C Belkina, Gerald V Denis
Several cancer clinical trials for small molecule inhibitors of BET bromodomain proteins have been initiated. There is enthusiasm for the anti-proliferative effect of inhibiting BRD4, one of the targets of these inhibitors, which is thought to cooperate with MYC, a long-desired target for cancer therapeutics. However, no current inhibitor is selective for BRD4 among the three somatic BET proteins, which include BRD2 and BRD3; their respective functions are partially overlapping and none are functionally redundant with BRD4...
March 2016: Drug Discovery Today. Technologies
Ester Fernandez-Salas, Shaomeng Wang, Arul M Chinnaiyan
Castration resistant prostate cancer (CRPC) is a deadly disease with few therapeutic options once patients become resistant to second generation drugs targeting the AR-transcriptional program. The BET-BRD readers of chromatin are key regulators of AR-, ERG-, and c-Myc-mediated transcription in CRPC. BET-BRD inhibitors have demonstrated pre-clinical efficacy in models of CRPC and are currently being evaluated in several clinical trials. These novel drugs have the potential to transform the way we treat CRPC in the near future...
March 2016: Drug Discovery Today. Technologies
Lei Shi, Wenfa Zhang, Fagui Zou, Lihua Mei, Gang Wu, Yong Teng
BACKGROUND: Hepatocellular carcinoma (HCC) has very high prevalence and associated-mortality. However, targeted therapies that are currently used in clinical practice for HCC have certain limitations, in part because of the lack of reliable and clinically applicable biomarkers that can be used for diagnosis and prognosis assessments and for the surveillance of treatment effectiveness. METHODS: Meta-analysis was used to analyze the integrated microarray data for global identification of a set of robust biomarkers for HCC...
October 21, 2016: BMC Cancer
Margarida Ferreira-Teixeira, Daniela Paiva-Oliveira, Belmiro Parada, Vera Alves, Vitor Sousa, Obinna Chijioke, Christian Münz, Flávio Reis, Paulo Rodrigues-Santos, Célia Gomes
BACKGROUND: High-grade non-muscle invasive bladder cancer (NMIBC) has a high risk of recurrence and progression to muscle-invasive forms, which seems to be largely related to the presence of tumorigenic stem-like cell populations that are refractory to conventional therapies. Here, we evaluated the therapeutic potential of Natural Killer (NK) cell-based adoptive immunotherapy against chemoresistant bladder cancer stem-like cells (CSCs) in a pre-clinical relevant model, using NK cells from healthy donors and NMIBC patients...
October 21, 2016: BMC Medicine
Mingdi Zhang, Wei Gong, Bin Zuo, Bingfeng Chu, Zhaohui Tang, Yong Zhang, Yong Yang, Di Zhou, Mingzhe Weng, Yiyu Qin, Mingzhe Ma, Alex Jiang, Fei Ma, Zhiwei Quan
Cytokine is a key molecular link between chronic inflammation and gallbladder cancer (GBC) progression. The potential mechanism of cytokine-associated modulation of microRNAs (miRNAs) expression in GBC progression is not fully understood. In this study, we investigated the biological effects and prognostic significance of interleukin-6 (IL-6) -induced miRNAs in the development of GBC. We identify that inflammatory cytokine, IL-6 promotes proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of GBC both in vitro and in vivo...
October 15, 2016: Oncotarget
Shuaihantian Luo, Yunuo Wang, Ming Zhao, Qianjin Lu
Systemic lupus erythematosus (SLE) is a severe autoimmune disease that causes multiple-organ dysfunction mainly affecting women in their childbearing years. Type I IFN synthesis is usually triggered by viruses, and its production is tightly regulated and limited in time in health individuals. However, many patients with systemic autoimmune diseases including SLE have signs of aberrant production of type I interferon (IFN) and display an increased expression of IFN-inducible genes. Continuous type I IFNs derived from activated plasmacytoid dendritic cells (pDCs) by interferogenic immune complexes (ICs) and migration of these cells to tissues both break immune tolerance and promote an on-going autoimmune reaction in human body...
October 18, 2016: International Immunopharmacology
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