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Pre-clinical studies

Rui Feng, Liyang Wang, Zhonguang Li, Rong Yang, Yu Liang, Yuting Sun, Qiuxia Yu, George Ghartey-Kwansah, Yanping Sun, Yajun Wu, Wei Zhang, Xin Zhou, Mengmeng Xu, Joseph Bryant, Guifang Yan, William Isaacs, Jianjie Ma, Xuehong Xu
Cardiovascular disease (CVD) is a major global cause of mortality, which has prompted numerous studies seeking to reduce the risk of heart failure and sudden cardiac death. While regular physical activity is known to improve CVD associated morbidity and mortality, the optimal duration, frequency, and intensity of exercise remains unclear. To address this uncertainty, various animal models have been used to study the cardioprotective effects of exercise and related molecular mechanism such as the mice training models significantly decrease size of myocardial infarct by affecting Kir6...
December 2, 2018: Life Sciences
A D Burns, D Lane, R Cole, P Patel, P Gupta
Biochemical testing in urine is a powerful new tool in the investigation of non-adherence to cardiovascular medications Drug testing using liquid chromatography tandem mass spectrometry (LC-MS-MS) is the mainstay of the laboratory test but may be subject to pre-analytical factors that could impact on test results. The stability of cardiovascular medications in urine is one such factor that has not been fully explored in non-adherence testing and has the potential to result in patients appearing falsely non-adherent to their therapy...
December 5, 2018: Journal of Analytical Toxicology
Antônio Rafael da Silva, Pedro Martins Lima Neto, Leonardo Hunaldo Dos Santos, Raina Jansen Cutrim Propp Lima, Pedro Luiz Tauil, Eloísa da Graça do Rosário Gonçalves
INTRODUCTION: The Integrated Program of Leprosy Control was initiated in the municipality of Buriticupu, Maranhão, Brazil, an area considered hyperendemic for leprosy in 2003. It aims at assessing the clinical and epidemiological characteristics of the disease to reduce the detection rate of new cases until 2015. Here, we present the evolution of the indicators of leprosy within the period from 2003 to 2015. METHODS: We conducted a descriptive analytical study based on the active search for and voluntary referral of cases of leprosy...
November 2018: Revista da Sociedade Brasileira de Medicina Tropical
Mike R Bueno, Carlos Estrela, Brunno C Azevedo, Anibal Diogenes
Cone-beam computed tomography (CBCT) has promoted changes in approaches in Endodontics, and enhanced decision-making in complex clinical cases. Despite the technological advancements in CBCT hardware, the interpretation of the acquired images is still compromised by viewing software packages that often have limited navigational tools and lack adequate filters to overcome some challenges of the CBCT technology such as artefacts. This study reviews the current limitations of CBCT and the potential of a new CBCT software package (e-Vol DX, CDT- Brazil) to overcome these aspects and support diagnosing, planning and managing of endodontic cases...
November 2018: Brazilian Dental Journal
Pedro Bichaff, Karina T Setani, Emiliana H G Motta, Artur F Delgado, Werther B Carvalho, Michele Luglio
OBJECTIVE: Opioid abstinence syndrome is common in the pediatric intensive care environment because sedation is often needed during the children's treatment. There is no specific guideline regarding the management of these patients; and lately, methadone is an important drug for the prevention of abstinence symptoms during the weaning of opioids. This study gathers the available research to establish the initial dose of methadone, the rate of taper and tools to recognize this syndrome and act promptly...
October 2018: Revista da Associação Médica Brasileira
Koray K Demir, Matthew P Cheng, Todd C Lee
INTRODUCTION AND OBJECTIVE: Diagnostic testing for Clostridioides difficile infection (CDI) by nucleic acid amplification test (NAAT) cannot distinguish between colonization and infection. A positive NAAT may therefore represent a false positive for infection, since diarrhea due to various aetiologies may occur in hospitalized patients. Our objective was to help answer the question: "does this medical inpatient with diarrhea have CDI?" DESIGN: We conducted a retrospective cohort study (n = 248) on the Clinical Teaching Units of the Royal Victoria Hospital (Montréal, Canada)...
2018: PloS One
Łukasz Cieszyński, Jarosław Jendrzejewski, Piotr Wiśniewski, Anna Owczarzak, Krzysztof Sworczak
BACKGROUND: Measuring hair cortisol seems to be a good alternative to laboratory tests used thus far in routine endocrine diagnostics, primarily because it is independent of the circadian rhythm of cortisol. Due to the average hair growth of 1 cm per month, the results are related to the average blood cortisol levels over the previous weeks, months or years (depending on the length of the hair sample). OBJECTIVES: The aim of this study is an attempt to apply hair cortisol concentration (HCC) measurements to clinical endocrine diagnostics, based on reference cortisol concentrations in the blood in a population without disorders of the hypothalamic-pituitary-adrenal axis (HPA)...
December 5, 2018: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Stefan Harth, Andre Ten Haaf, Christian Loew, Christian Frisch, Achim Knappik
Anti-idiotypic antibodies play an important role in pre-clinical and clinical development of therapeutic antibodies, where they are used for pharmacokinetic studies and for the development of immunogenicity assays. By using an antibody phage display library in combination with guided in vitro selection against various marketed drugs, we generated antibodies that recognize the drug only when bound to its target. We have named such specificities Type 3, to distinguish them from the anti-idiotypic antibodies that specifically detect free antibody drug or total drug...
December 5, 2018: MAbs
Joshua D Moss, Adam Oesterle, Michael Raiman, Erin E Flatley, Andrew D Beaser, Valluvan Jeevanandam, Liviu Klein, Takeyoshi Ota, Georg Wieselthaler, Nir Uriel, Roderick Tung
INTRODUCTION: Ventricular arrhythmias (VA) after left ventricular assist device (LVAD) placement are associated with increased morbidity and mortality. We sought to assess epicardial voltage characteristics at the time of LVAD implantation and investigate relationships between scar burden and post-implant VA. METHODS AND RESULTS: Consecutive patients underwent open-chest epicardial electroanatomic mapping immediately prior to LVAD implantation. Areas of low voltage and sites with local abnormal potentials were identified...
December 5, 2018: Journal of Cardiovascular Electrophysiology
Verena Hampel, Martin Knaus, Jürgen Schäfer, Frederic Beugnet, Steffen Rehbein
The efficacy of NexGard® and NexGard Spectra® against sarcoptic mange in dogs was evaluated in a clinical field study. Skin scrapings from dogs presenting signs suggestive of sarcoptic mange were examined to confirm infestation. A total of 106 dogs were screened at eight sites in Portugal and Germany. In all, 80 dogs that had demonstrated ≥5 live Sarcoptes mites in five skin scrapings were enrolled, scored for specific clinical signs (pruritus; papules and crusts; alopecia), and allocated at random to receive either NexGard® or NexGard Spectra® twice, one month apart per label instructions...
2018: Parasite: Journal de la Société Française de Parasitologie
Peter P Karpawich
Cardiac resynchronization pacing therapy (CRT) can be a potentially effective modality to delay the need for heart transplantation and improve the clinical status among patients with heart failure. Unfortunately, published guidelines and studies with an over-reliance on ejection fraction (EF) and QRS duration as markers for efficacy are frequently not applicable to the ever-growing number of adults with repaired congenital heart defects (CHD), some with systemic anatomical right ventricles as well as pre-existing pacemakers...
December 4, 2018: Pacing and Clinical Electrophysiology: PACE
Talia Donenberg, Sophia George, Jameel Ali, Gabriela Bravo, Karen Hernandez, Navin Sookar, Kimlin Tam Ashing, Steven A Narod, Mohammad R Akbari, Judith Hurley
INTRODUCTION: Breast cancer (BC) is the leading cause of cancer death in Caribbean women. Across the Caribbean islands, the prevalence of hereditary breast cancer among unselected breast cancer patients ranges from 5 to 25%. Moreover, the prevalence of BC among younger women and the high mortality in the Caribbean region are notable. This BC burden presents an opportunity for cancer prevention and control that begins with genetic testing among high-risk women. Measured response to positive genetic test results includes the number of preventive procedures and cascade testing in family members...
December 4, 2018: Breast Cancer Research and Treatment
Victoria Pilkington, Andrew Hill, Sophie Hughes, Nneka Nwokolo, Anton Pozniak
Background: Tenofovir/emtricitabine (TDF/FTC) used as pre-exposure prophylaxis (PrEP) has proven benefits in preventing HIV infection. Widespread use of TDF/FTC can only be justified if the preventative benefits outweigh potential risks of adverse events. A previous meta-analysis of TDF/FTC compared to alternative tenofovir alafenamide (TAF)/FTC for treatment found no significant difference in safety endpoints when used without ritonavir or cobicistat, but more evidence around the safety of TDF/FTC is needed to address concerns and inform widespread use...
October 1, 2018: Journal of Virus Eradication
Violet Kasabri, Esraa Shawakri, Amal Akour, Randa Naffa, Nahla Khawaja, Ibrahim Al-Sarraf, Jameel Bzour
Background: Oxytocin (OXT), fetuin-A and interleukin-18 (IL-18) are involved in the development and progression of metabolic syndrome (MetS) and prediabetes (pre/T2DM). Aims participants and methods: This study aimed to compare and correlate the plasma levels of OXT, fetuin-A and IL-18 with clinical parameters, haematological indices and adiposity indices in Jordanian MetS subjects. In a cross-sectional study, 30 normoglycaemic lean study participants (control), 30 MetS study participants, and 29 MetS pre/T2DM study participants were recruited...
December 2018: Therapeutic Advances in Endocrinology and Metabolism
Paul Lohan, Nick Murphy, Oliver Treacy, Kevin Lynch, Maurice Morcos, Bingling Chen, Aideen E Ryan, Matthew D Griffin, Thomas Ritter
High-risk cornea transplant recipients represent a patient population with significant un-met medical need for more effective therapies to prevent immunological graft rejection due to heightened anti-donor immune response. In this study, a rat model of pre-existing anti-donor immunity was developed in which corneal allografts were rejected earlier than in non-pre-sensitized recipients. In this model, third-party (non-donor, non-recipient strain) allogeneic mesenchymal stromal cells (allo-MSC) were administered intravenously 7 and 1 days prior to transplantation...
2018: Frontiers in Immunology
Marie Furuta, Antje Horsch, Edmond S W Ng, Debra Bick, Debbie Spain, Jacqueline Sin
Background: Approximately 3% of women in community samples develop posttraumatic stress disorder (PTSD) after childbirth. Higher prevalence rates are reported for high risk samples. Postpartum PTSD can adversely affect women's wellbeing, mother-infant relationships and child development. This study aims to examine the effectiveness of trauma-focused psychological interventions (TFPT), for postnatal women. Methods: We conducted a systematic review and meta-analysis including all clinical trials which reported post-traumatic stress symptoms for both the intervention and control groups or at least two time-points, pre- and post-intervention...
2018: Frontiers in Psychiatry
Kenichiro Yamamura, Darren Yuen, Edward J Hickey, Xiaolin He, Rajiv R Chaturvedi, Mark K Friedberg, Lars Grosse-Wortmann, Kate Hanneman, Filio Billia, Michael E Farkouh, Rachel M Wald
OBJECTIVE: The relationship between right ventricular (RV) fibrosis and right heart reverse remodelling following pulmonary valve replacement (PVR) has not been well studied in adults with repaired tetralogy of Fallot (rTOF). Our aims were to histologically quantify RV fibrosis and to explore the relationship between fibrosis severity and cardiac remodelling post-PVR. METHODS: Adults with rTOF and pre-PVR cardiovascular (CMR) imaging were consented to procurement of RV muscle during PVR...
December 4, 2018: Heart: Official Journal of the British Cardiac Society
Piers Blombery, Mary Ann Anderson, Jia-Nan Gong, Rachel Thijssen, Richard W Birkinshaw, Ella R Thompson, Charis E Teh, Tamia Nguyen, Zhen Xu, Christoffer Flensburg, Thomas E Lew, Ian J Majewski, Daniel H D Gray, David A Westerman, Constantine S Tam, John F Seymour, Peter E Czabotar, David C S Huang, Andrew W Roberts
The BCL2 inhibitor, venetoclax, induces high rates of durable remission in patients with previously treated chronic lymphocytic leukemia (CLL). However, despite continuous daily treatment, leukemia recurs in most patients. To investigate the mechanisms of secondary resistance, we analyzed paired pre-venetoclax and progression samples from 15 patients with CLL progression enrolled on venetoclax clinical trials. The novel Gly101Val mutation in BCL2 was identified at progression in seven patients, but not at study entry...
December 4, 2018: Cancer Discovery
Pramod Kumar Gupta, Savita Kulkarni
Plethora of clinical and scientific information obtained in recent past has strengthened the idea that targeting critical constituents of host immune system may have beneficial outcomes for the treatment of tuberculosis. Macrophages being the primary host for Mycobacterium tuberculosis, offer an attractive target for modulation. Owing to their negligible toxicity, plant derived polysaccharides with the ability to activate macrophages; are suitable candidates for immunomodulation. In the present study, effects of polysaccharide rich extract (PRE) isolated from Tinospora cordifolia, on the survival of intracellular MTB strains and activation of macrophages were investigated...
December 2018: Tuberculosis
Hari Krishna Ananthula, Scott Parker, Erin Touchette, R Mark Buller, Gopi Patel, Daniel Kalman, Johanna S Salzer, Nadia Gallardo-Romero, Victoria Olson, Inger K Damon, Tessa Moir-Savitz, Larry Sallans, Milton H Werner, Catherine M Sherwin, Pankaj B Desai
BACKGROUND: Several tyrosine kinase inhibitors (TKIs) developed as anti-cancer drugs, also have anti-viral activity due to their ability to disrupt productive replication and dissemination in infected cells. Consequently, such drugs are attractive candidates for "repurposing" as anti-viral agents. However, clinical evaluation of therapeutics against infectious agents associated with high mortality, but low or infrequent incidence, is often unfeasible. The United States Food and Drug Administration formulated the "Animal Rule" to facilitate use of validated animal models for conducting anti-viral efficacy studies...
December 4, 2018: BMC Pharmacology & Toxicology
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