BLU-5937: A selective P2X3 antagonist with potent anti-tussive effect and no taste alteration

In conclusion, BLU-5937 was selected as a drug candidate for the treatment of chronic cough due to its high potency and selectivity for P2X3 homotrimeric receptors, strong anti-tussive effects, excellent tolerability and predicted pharmacokinetic properties in humans.
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research

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Authors: Mian A, Singal AK, Bakhshi S, Sood R, Vikram NK, Ray A Abstract A 21-year old female, recently diagnosed with osteosarcoma of right humerus, presented to the emergency with history of fever, productive cough, chest pain and progressive respiratory distress for six days. Initial investigations suggested pneumonia but she did not respond to parenteral antibiotics. CT pulmonary angiogram revealed bilateral pulmonary artery embolism. Thrombolysis was performed using alteplase, which failed to improve the clinical condition. In view of underlying malignancy, a possibility of tumour-embolism was considered and s...
Source: Journal of the Association of Physicians of India - Category: General Medicine Tags: J Assoc Physicians India Source Type: research
Authors: Sharma R, Mahajan SK, Singh B, Raina R, Kanga A Abstract Aims: To study predictors of severity in patients of scrub typhus admitted in a tertiary care hospital. Material and Methods: Total 92 patients of scrub typhus were included in the study. The diagnosis was established by presence of IgM antibodies by Indirect Immunofluorescence Assay (IFA) test which is currently the reference standard for the diagnosis of scrub typhus. The clinical and laboratory profile, course in hospital, and outcome were documented. Factors associated with severe disease were analyzed. Observations: Fever (100%), cough (...
Source: Journal of the Association of Physicians of India - Category: General Medicine Tags: J Assoc Physicians India Source Type: research
ConclusionsOur findings demonstrate that DOI blocks ethanol place conditioning and selectively reduces voluntary ethanol consumption. This may be related to modulation of the effects of ethanol in the reward circuitry of the brain, ethanol-induced neuroinflammation, or a combination of both. Additional studies to elucidate the mechanisms through which psychedelics attenuate the effects of ethanol would inform the pathophysiology of AUD and potentially provide new treatment options.
Source: Psychopharmacology - Category: Psychiatry Source Type: research
In this study, we aimed to investigate the protective effects and underlying antitussive mechanisms of Suhuang on pulmonary function in ovalbumin (OVA)-induced CVA rats. Administration (i.g.) of Suhuang significantly alleviated pulmonary damage and dysfunction. Suhuang improved ER stress and PKCε translocation via regulation of Ca2+ trafficking. Suhuang also inhibited NLRP3 inflammasome activation, as evidenced by disrupting the assembly of NLRP3 inflammasome and reducing the expression of cleaved caspase-1, and decreased IL-1β secretion. Besides, it’s identified that TXNIP induction and RIP1-RIP3-Drp1 p...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Abstract The allergic airway diseases, including chronic rhinosinusitis (CRS), asthma, allergic bronchopulmonary mycosis (ABPM) and many others, comprise a heterogeneous collection of inflammatory disorders affecting the upper and lower airways and lung parenchyma that represent the most common chronic diseases of humanity. In addition to their shared tissue tropism, the allergic airway diseases are characterized by a distinct pattern of inflammation involving the accumulation of eosinophils, type 2 macrophages, innate lymphoid cells type 2 (ILC2), IgE-secreting B cells, and T helper type 2 (Th2) cells in airway t...
Source: Advances in Immunology - Category: Allergy & Immunology Authors: Tags: Adv Immunol Source Type: research
In conclusion, there is a close association between peripheral nerve terminals and a population of nonneuronal cells that express GFR α3 in the bone marrow. The nonneuronal cells have characteristics consistent with a neural crest-derived, nonmyelinating Schwann cell phenotype. Our findings provide a better understanding of the expression pattern of GFRα3 in the bone marrow microenvironment.
Source: Cell and Tissue Research - Category: Cytology Source Type: research
Publication date: Available online 13 July 2019Source: Molecular Phylogenetics and EvolutionAuthor(s): Ying Jiang, Min Gao, Ying Meng, Jun Wen, Xue-Jun Ge, Ze-Long NieAbstractThe Northern Hemisphere was widely covered by a tropical flora (i.e., the Boretropical flora) in the Eocene and the evaluation of plant diversifications in the post-Boreotropical era has become an important challenge to understanding the modern biogeographic complexity in this vast region. Toxicodendron or the poison ivy genus of the sumac family has a temperate to tropical distribution in Asia and North America and can serve as an excellent model for...
Source: Molecular Phylogenetics and Evolution - Category: Molecular Biology Source Type: research
Authors: Nishitani A, Yoshihara T, Tanaka M, Kuwamura M, Asano M, Tsubota Y, Kuramoto T Abstract Hyperpolarization-activated cyclic nucleotide-gated 1 (HCN1) channels contribute to spontaneous rhythmic activity in different tissues, including the heart and brain. Deficiency in HCN1 function is associated with sick sinus syndrome in mice and epilepsy in humans. We recently developed Hcn1-deficient rats and found that they exhibit absence epilepsy. While rearing Hcn1-deficient rats, we noticed loose muscle tension and abnormal gait. We therefore evaluated the muscle strength and motor functions of Hcn1-deficient rats...
Source: Experimental Animals - Category: Research Tags: Exp Anim Source Type: research
Conclusion. We provide a molecular mechanism for the activation of pain signals based on AMPK-mTOR axis, as well as an intervention strategy by targeting AMPK-mTOR axis in LDH-induced painful radiculopathies. Level of Evidence: N/A
Source: Spine - Category: Orthopaedics Tags: BASIC SCIENCE Source Type: research
We examined the distribution of TRPM3, P2X2&P2X3 in single airway neurons.Airway terminating neurons isolated from GPs were individually harvested &single-cell gene expression evaluated.P2X3 was expressed in 23/32 Jugular (J) &22/37 Nodose (N) neurons, P2X2 was expressed in 1/32 J &16/37 N, &P2X2 was co-expressed in 15/47 P2X3 neurons. Most A-fibres originate from the N ganglion, where P2X2/3 co-expression was predominant, and most C-fibres originate from the J ganglion where P2X3 was predominant. TRPM3 was expressed on 22/32 J and 14/37 N neurons, and co-expressed in 34/49 P2X expressing neurons.These resu...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Airway Pharmacology and Treatment Source Type: research
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