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https://www.readbyqxmd.com/read/29332144/long-acting-%C3%AE-2-agonists-in-asthma-enantioselective-safety-studies-are-needed
#1
Glenn A Jacobson, Sharanne Raidal, Morten Hostrup, Luigino Calzetta, Richard Wood-Baker, Mark O Farber, Clive P Page, E Haydn Walters
Long-acting β2-agonists (LABAs) such as formoterol and salmeterol are used for prolonged bronchodilatation in asthma, usually in combination with inhaled corticosteroids (ICSs). Unexplained paradoxical asthma exacerbations and deaths have been associated with LABAs, particularly when used without ICS. LABAs clearly demonstrate effective bronchodilatation and steroid-sparing activity, but long-term treatment can lead to tolerance of their bronchodilator effects. There are also concerns with regard to the effects of LABAs on bronchial hyperresponsiveness (BHR), where long-term use is associated with increased BHR and loss of bronchoprotection...
January 13, 2018: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/29331665/blocking-lpa-dependent-signaling-increases-ovarian-cancer-cell-death-in-response-to-chemotherapy
#2
LeAnn C Rogers, Ryan R Davis, Naveen Said, Thomas Hollis, Larry W Daniel
The paradoxical role of reactive oxygen species in cell death versus cell survival establishes a delicate balance between chemotherapy efficacy and management of detrimental side effects. Normal proliferative signaling requires that cells remain inside a redox range that allows reversible protein oxidation to occur. Shifting the redox environment toward highly reducing or oxidizing states leads to cellular stress and cell death. Reactive oxygen species produced in response to Taxol and cisplatin treatment are necessary for effective cancer cell killing but the same ROS leads to damaging side effects in normal tissues...
January 4, 2018: Redox Biology
https://www.readbyqxmd.com/read/29331642/protein-adaptations-in-extremophiles-an-insight-into-extremophilic-connection-of-mycobacterial-proteome
#3
REVIEW
Ashutosh Kumar, Anwar Alam, Deeksha Tripathi, Mamta Rani, Hafeeza Khatoon, Saurabh Pandey, Nasreen Z Ehtesham, Seyed E Hasnain
The biological paradox about how extremophiles persist at extreme ecological conditions throws a fascinating picture of the enormous potential of a single cell to adapt to homeostatic conditions in order to propagate. Unicellular organisms face challenges from both environmental factors and the ecological niche provided by the host tissue. Although the existence of extremophiles and their physiological properties were known for a long time, availability of whole genome sequence has catapulted the study on mechanisms of adaptation and the underlying principles that have enabled these unique organisms to withstand evolutionary and environmental pressures...
January 10, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29331050/exercise-counteracts-lipotoxicity-by-improving-lipid-turnover-and-lipid-droplet-quality
#4
Evelyn Zacharewicz, Matthijs K C Hesselink, Patrick Schrauwen
The incidence of obesity and metabolic disease, such as type 2 diabetes mellitus (T2D), are rising globally. Dietary lipid over-supply leads to lipid accumulation at ectopic sites, such as skeletal muscle. Ectopic lipid storage is highly correlated with insulin resistance and T2D, likely due to a loss of metabolic flexibility - the capacity to switch between fat and glucose oxidation upon insulin stimulation - and cellular dysfunction because of lipotoxicity. However, muscle lipid levels are also elevated in endurance trained athletes, presenting a paradoxical phenotype of increased intramuscular lipids along with high insulin sensitivity - the "athletes' paradox"...
January 13, 2018: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29330673/vacuum-assisted-closure-therapy-of-paradoxical-reaction-in-tuberculous-lymphadenopathy-caused-by-mycobacterium-africanum
#5
H F Geerdes-Fenge, P Pongratz, J Liese, E C Reisinger
A 26-year-old HIV-negative male from Ghana was treated for cervical, intrathoracic and abdominal lymph node tuberculosis (TB) and tuberculous hepatitis. Penetration of the thoracic trachea by a mediastinal lymph node had caused bronchomucosal TB. Sputum culture grew M. africanum, sensitive to all first-line antituberculous drugs. Four weeks after the beginning of directly observed treatment with isoniazid, rifampin, pyrazinamide and ethambutol, the right cervical lymph node increased in size, liquefied and caused a spontaneous fistula...
January 12, 2018: Infection
https://www.readbyqxmd.com/read/29330091/cdc42ep4-a-perisynaptic-scaffold-protein-in-bergmann-glia-is-required-for-glutamatergic-tripartite-synapse-configuration
#6
Natsumi Ageta-Ishihara, Kohtarou Konno, Maya Yamazaki, Manabu Abe, Kenji Sakimura, Masahiko Watanabe, Makoto Kinoshita
Configuration of tripartite synapses, comprising the pre-, post-, and peri-synaptic components (axon terminal or bouton, dendritic spine, and astroglial terminal process), is a critical determinant of neurotransmitter kinetics and hence synaptic transmission. However, little is known about molecular basis for the regulation of tripartite synapse morphology. Previous studies showed that CDC42EP4, an effector protein of a cell morphogenesis regulator CDC42, is expressed exclusively in Bergmann glia in the cerebellar cortex, that it forms tight complex with the septin heterooligomer, and that it interacts indirectly with the glutamate transporter GLAST and MYH10/nonmuscle myosin ΙΙB...
January 9, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29328038/quantitative-assessment-of-the-results-of-vimentin-immunohistochemical-examination-in-fibroblasts-and-endotheliocytes-of-the-placental-villi-in-the-aspect-of-preterm-maturation-of-the-chorionic-tree-and-iron-deficiency-anemia-of-gravidas
#7
О Garvasiuk, І Davydenko
The objective of our study was to investigate quantitative parameters of vimentin in fibroblasts and endotheliocytes of the chorionic villi by means of immunohistochemical examination of placenta with preterm maturation of the chorionic tree with iron-deficiency anemia of pregnancy in two different terms of gestation - 29-32 weeks and 33-36 weeks. 182 placentas were examined. The study design included two main groups of investigation of the above terms of gestation and three groups of comparison. Quantitative parameters of vimentin in the cytoplasm of fibroblasts and endotheliocytes of the placenta intermediate and terminal villi were considered on the basis of staining optic density measured by means of computer microdensitometry method...
December 2017: Georgian Medical News
https://www.readbyqxmd.com/read/29328011/-is-there-quality-of-life-with-locked-in-syndrome
#8
S D Limburg, J Pols, M Limburg
A 57-year-old man developed a locked-in state due to a brain stem stroke. He communicated through eye movements. The team suggested treatment should be discontinued, as there was no perspective of improvement. The family was very upset because they experienced sufficient quality of life. We investigated what 'quality of life' means. The literature shows that severely ill and completely care-dependent patients may experience high quality of life; this is called the disability paradox. Patients and families evaluate quality of life by looking for positive things to live for...
2018: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/29327600/population-based-serum-omentin-1-levels-paradoxical-association-with-cardiometabolic-disorders-primarily-in-men
#9
Altan Onat, Evin Ademoglu, Yusuf Karadeniz, Gunay Can, Ahmet Okan Uzun, Barıs Simsek, Aysem Kaya
AIM: The conflicting relationships of serum omentin with inflammation markers and cardiometabolic disorders were investigated. Results & methodology: Unselected 864 population-based middle-aged adults were cross-sectionally studied by sex-specific omentin tertiles. Men in the lowest omentin tertile (T1) had lower systolic blood pressure, HbA1c and glucose values and tended in T3 to higher lipoprotein(a) levels. Logistic regression analysis, adjusted for four covariates, revealed significant independent associations with the presence of hypertension and diabetes only in men...
January 12, 2018: Biomarkers in Medicine
https://www.readbyqxmd.com/read/29327091/temporal-fluctuations-in-behavior-perceived-hiv-risk-and-willingness-to-use-pre-exposure-prophylaxis-prep
#10
Kristen Underhill, Kate M Guthrie, Christopher Colleran, Sarah K Calabrese, Don Operario, Kenneth H Mayer
Individual perceptions of HIV risk influence willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention. Among men who have sex with men (MSM) and male sex workers (MSWs), temporal or episodic changes in risk behavior may influence perceived risk and PrEP acceptability over time. We investigated fluctuations in perceived HIV risk and PrEP acceptability, comparing MSWs against MSM who do not engage in sex work. We conducted 8 focus groups (n = 38) and 56 individual interviews among MSM and MSWs in Providence, RI...
January 11, 2018: Archives of Sexual Behavior
https://www.readbyqxmd.com/read/29326369/successful-treatment-of-postural-orthostatic-tachycardia-and-mast-cell-activation-syndromes-using-naltrexone-immunoglobulin-and-antibiotic-treatment
#11
Leonard B Weinstock, Jill B Brook, Trisha L Myers, Brent Goodman
A patient with severe postural orthostatic tachycardia syndrome (POTS) and mast cell activation syndrome (MCAS) received immunotherapy with low-dose naltrexone (LDN) and intravenous immunoglobulin (IVIg) and antibiotic therapy for small intestinal bacterial overgrowth (SIBO). A dramatic and sustained response was documented. The utility of IVIg in autoimmune neuromuscular diseases has been published, but clinical experience with POTS is relatively unknown and has not been reported in MCAS. As a short-acting mu-opioid antagonist, LDN paradoxically increases endorphins which then bind to regulatory T cells which regulate T-lymphocyte and B-lymphocyte production and this reduces cytokine and antibody production...
January 11, 2018: BMJ Case Reports
https://www.readbyqxmd.com/read/29326249/in-pakistan-surveillance-for-polio-reveals-a-paradox
#12
Leslie Roberts
No abstract text is available yet for this article.
January 12, 2018: Science
https://www.readbyqxmd.com/read/29325444/redox-paradox-a-novel-approach-to-therapeutics-resistant-cancer
#13
Luksana Chaiswing, William H St Clair, Daret K St Clair
Cancer cells that are resistant to radiation and chemotherapy are a major problem limiting the success of cancer therapy. Aggressive cancer cells depend on elevated intracellular levels of reactive oxygen species (ROS) to proliferate, self-renew, and metastasize. As a result, these aggressive cancers maintain high basal levels of ROS compared to normal cells. The prominence of the redox state in cancer cells led us to consider whether increasing the redox state to the condition of oxidative stress could be used as a successful adjuvant therapy for aggressive cancers...
January 12, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29325166/drug-safety-and-immunogenicity-of-tumour-necrosis-factor-inhibitors-the-story-so-far
#14
Meghna Jani, William G Dixon, Hector Chinoy
TNF-α inhibitor (TNFi) therapies have transformed the treatment of several rheumatic musculoskeletal diseases. However, the majority of TNFi's are immunogenic and consequent anti-drug antibodies formation can impact on both treatment efficacy and safety. Several controversies exist in the area of immunogenicity of TNFis and drug safety. While anti-drug antibodies to TNFis have been described in association with infusion reactions; serious adverse events (AEs) such as thromboembolic events, lupus-like syndrome, paradoxical AEs, for example, vasculitis-like events and other autoimmune manifestations have also been reported...
January 8, 2018: Rheumatology
https://www.readbyqxmd.com/read/29324302/addressing-the-paradox-of-increasing-mastectomy-rates-in-an-era-of-de-escalation-of-therapy-communication-strategies
#15
REVIEW
Mona P Tan, Edibaldo Silva
Breast conservation therapy (BCT) was established as the preferred modality of surgical treatment for early stage breast cancer in the early 1990's. Yet, rising mastectomy rates have been observed over the last decade. This increase is a cause for concern as recent large population-based studies have consistently reported improved breast cancer-specific survival and local control rates with BCT, in comparison with mastectomy. There is a pressing need to formulate strategies to effectively inform both patients and practitioners about current data, in the hope of reversing rising mastectomy rates to optimise survival outcomes...
January 8, 2018: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/29323712/paradoxical-side-effects-of-bisphosphonates-on-the-skeleton-what-do-we-know-and-what-can-we-do
#16
REVIEW
Jorge William Vargas-Franco, Beatriz Castaneda, Françoise Rédiní, David Francisco Gómez, Dominique Heymann, Frédéric Lézot
Bisphosphonates are considered the most effective drugs for controlling adult and pediatric osteolytic diseases. Although they have been used successfully for many years, several side effects, such as osteonecrosis of the jaw, delayed dental eruption, atypical femoral fracture and alterations to the bone growth system, have been described. After an overview of nitrogenous bisphosphonate, the purpose of this article is to describe their mechanisms of action and current applications, review the preclinical and clinical evidence of their side effects in the skeleton ("what we know"), and describe current recommendations for preventing and managing these effects ("what we can do")...
January 11, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29323282/mll2-conveys-transcription-independent-h3k4-trimethylation-in-oocytes
#17
Courtney W Hanna, Aaron Taudt, Jiahao Huang, Lenka Gahurova, Andrea Kranz, Simon Andrews, Wendy Dean, A Francis Stewart, Maria Colomé-Tatché, Gavin Kelsey
Histone 3 K4 trimethylation (depositing H3K4me3 marks) is typically associated with active promoters yet paradoxically occurs at untranscribed domains. Research to delineate the mechanisms of targeting H3K4 methyltransferases is ongoing. The oocyte provides an attractive system to investigate these mechanisms, because extensive H3K4me3 acquisition occurs in nondividing cells. We developed low-input chromatin immunoprecipitation to interrogate H3K4me3, H3K27ac and H3K27me3 marks throughout oogenesis. In nongrowing oocytes, H3K4me3 was restricted to active promoters, but as oogenesis progressed, H3K4me3 accumulated in a transcription-independent manner and was targeted to intergenic regions, putative enhancers and silent H3K27me3-marked promoters...
January 2018: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/29321947/portal-vein-thrombosis-due-to-an-increase-in-dose-of-testosterone-in-a-young-man-with-klinefelter-syndrome
#18
Waseem Amjad, Salma Khatoon, Twara Tarasaria, Gulru Sharifova
Klinefelter syndrome (KS) is associated with increased incidence of thrombotic events. Hypofibrinolysis is associated with increased risk of thromboembolism. Although testosterone replacement therapy (TRT) inhibits the hypofibrinolysis, it can still cause thrombosis paradoxically due to increased dose and duration of use. Herein, we present a case of a young male diagnosed with KS who was taking testosterone. The dose was increased to boost the energy levels, and the patient presented with abdominal pain. Computed tomography (CT) of the abdomen showed extensive portal vein thrombosis...
November 6, 2017: Curēus
https://www.readbyqxmd.com/read/29321933/acute-progression-of-aspergillosis-in-a-patient-with-lung-cancer-receiving-nivolumab
#19
Naohiro Uchida, Kohei Fujita, Koichi Nakatani, Tadashi Mio
A 65-year-old man with chronic progressive pulmonary aspergillosis (CPPA) was admitted for the treatment of lung adenocarcinoma while receiving an immune checkpoint inhibitor, nivolumab. The tumour responded well to the therapy, but the cavity of CPPA became large in contrast to the tumour after 20 courses of therapy. He was diagnosed as having exacerbation of CPPA and successfully and concurrently treated with an antifungal agent and nivolumab. Since there was absence of obvious immunosuppression and the presence of a drastic effect on tumour remission during nivolumab therapy, this phenomenon suggested that the trigger of CPPA progression was dependent not on immunosuppression but on a hyperreaction to microorganisms, which was similar to the immune reconstitution inflammatory syndrome caused by nivolumab...
February 2018: Respirology Case Reports
https://www.readbyqxmd.com/read/29321594/estimating-the-capacity-for-production-of-formamide-by-radioactive-minerals-on-the-prebiotic-earth
#20
Zachary R Adam, Yayoi Hongo, H James Cleaves, Ruiqin Yi, Albert C Fahrenbach, Isao Yoda, Masashi Aono
Water creates special problems for prebiotic chemistry, as it is thermodynamically favorable for amide and phosphodiester bonds to hydrolyze. The availability of alternative solvents with more favorable properties for the formation of prebiotic molecules on the early Earth may have helped bypass this so-called "water paradox". Formamide (FA) is one such solvent, and can serve as a nucleobase precursor, but it is difficult to envision how FA could have been generated in large quantities or accumulated in terrestrial surface environments...
January 10, 2018: Scientific Reports
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