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  • Searching for synergistic calcium antagonists and novel therapeutic regimens for coronary heart disease therapy from a Traditional Chinese Medicine, Suxiao Jiuxin Pill.

    Posted 2018-06-17 10:00:42 by: Mahammad A. Tafida

    Related Articles Searching for synergistic calcium antagonists and novel therapeutic regimens for coronary heart disease therapy from a Traditional Chinese Medicine, Suxiao Jiuxin Pill. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jun 08;1092:220-227 Authors: Lei W, Ni J, Xia X, Jiang M, Bai G Abstract Coronary heart disease is a vital cause of morbidity and mortality worldwide, and calcium channel blockers (CCBs) are important drugs that can be used to treat cardiovascular diseases. Suxiao Jiuxin Pill (SX), a traditional Chinese medicine, is widely used as an emergency drug for coronary heart disease therapy. However, understanding its potential mechanism in intracellular calcium concentration ([Ca2+]i) modulation remains a challenge. To identify the active pharmacological ingredients (APIs) and reveal a novel combination therapy for ameliorating cardiovascular diseases, the ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) combined with a dual-luciferase reporter [Ca2+]i assay system was applied. Ligustrazine, ferulic acid, senkyunolide I, senkyunolide A and ligustilide were identified as potential calcium antagonists in SX, and the combination of ligustrazine and senkyunolide A showed synergetic calcium antagonistic activity. Additionally, the synergetic mechanism was further investigated by live-imaging analysis with the Ca2+ indicator fluo-4/AM by monitoring fluorescence changes. Our results indicated that ligustrazine can block voltage-operated Ca2+ channels (VDCCs) effectively and senkyunolide A can exert an inhibition effect mostly on ryanodine receptors (RYRs) and partly on VDCCs. Finally, an arterial ring assay showed that the combination of ligustrazine and senkyunolide A exerted a better vasodilatation function than using any components alone. In this study, we first revealed that a pair of natural APIs in combination acting on VDCCs and RYRs ...

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  • Checklists in emergency medicine.

    Posted 2018-06-17 10:00:42 by: Mahammad A. Tafida

    Related Articles Checklists in emergency medicine. Emerg Med J. 2018 Jun 15;: Authors: Hearns S PMID: 29907603 [PubMed - as supplied by ...

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  • Aerosolized antibiotics: For prophylaxis or for treatment? - Authors' reply.

    Posted 2018-06-17 10:00:42 by: Mahammad A. Tafida

    Related Articles Aerosolized antibiotics: For prophylaxis or for treatment? - Authors' reply. J Crit Care. 2018 Jun 12;: Authors: Póvoa FCC, Cardinal-Fernandez P, Maia IS, Reboredo MM, Pinheiro BV PMID: 29907262 [PubMed - as supplied by ...

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  • Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy.

    Posted 2018-06-17 10:00:42 by: Mahammad A. Tafida

    Related Articles Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy. Blood. 2018 Jun 14;: Authors: Porpaczy E, Tripolt S, Hoelbl-Kovacic A, Gisslinger B, Bago-Horvath Z, Casanova-Hevia E, Clappier E, Decker T, Fajmann S, Fux DA, Greiner G, Gueltekin S, Heller G, Herkner H, Hoermann G, Kiladjian JJ, Kolbe T, Kornauth C, Krauth MT, Kralovics R, Muellauer L, Mueller M, Prchal-Murphy M, Putz EM, Raffoux E, Schiefer AI, Schmetterer K, Schneckenleithner C, Simonitsch-Klupp I, Skrabs C, Sperr WR, Staber PB, Strobl B, Valent P, Jaeger U, Gisslinger H, Sexl V Abstract Inhibition of Janus-kinase 1/2 (JAK1/2) is a mainstay to treat myeloproliferative neoplasms (MPN). Sporadic observations reported the co-incidence of B-cell non-Hodgkin lymphomas during treatment of MPN with JAK1/2 inhibitors. We assessed 626 MPN patients including 69 with myelofibrosis receiving JAK1/2 inhibitors for lymphoma development. B-cell lymphomas evolved in 4/69 patients (5.8%) upon JAK1/2 inhibition compared to 2/557 (0.36%) with conventional treatment (16-fold increased risk). A similar 15-fold increase was observed in an independent cohort of 929 MPN patients. Considering primary myelofibrosis only (N=216), 3 lymphomas were observed in 31 inhibitor-treated patients (9.7%) versus 1/185 controls (0.54%). Lymphomas were of aggressive B-cell type, extra-nodal or leukemic with high MYC expression in the absence of JAK2 V617F or other MPN-associated mutations. Median time from initiation of inhibitor therapy to lymphoma diagnosis was 25 months. Clonal immunoglobulin gene rearrangements were already detected in the bone marrow during myelofibrosis in 16.3% of patients. Lymphomas occurring during JAK1/2 inhibitor treatment were preceded by a pre-existing B-cell clone in all 3 patients tested. Sequencing verified clonal identity in 2 patients. The effects of JAK1/2 inhibition were mirrored in Stat1-/- mice: ...

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  • Avoiding Respiratory and Peripheral Muscle Injury During Mechanical Ventilation: Diaphragm-Protective Ventilation and Early Mobilization.

    Posted 2018-06-17 10:00:42 by: Mahammad A. Tafida

    Related Articles Avoiding Respiratory and Peripheral Muscle Injury During Mechanical Ventilation: Diaphragm-Protective Ventilation and Early Mobilization. Crit Care Clin. 2018 Jul;34(3):357-381 Authors: Schreiber A, Bertoni M, Goligher EC Abstract Both limb muscle weakness and respiratory muscle weakness are exceedingly common in critically ill patients. Respiratory muscle weakness prolongs ventilator dependence, predisposing to nosocomial complications and death. Limb muscle weakness persists for months after discharge from intensive care and results in poor long-term functional status and quality of life. Major mechanisms of muscle injury include critical illness polymyoneuropathy, sepsis, pharmacologic exposures, metabolic derangements, and excessive muscle loading and unloading. The diaphragm may become weak because of excessive unloading (leading to atrophy) or because of excessive loading (either concentric or eccentric) owing to insufficient ventilator assistance. PMID: 29907270 [PubMed - in ...

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  • Radiotherapy for Langerhans cell histiocytosis with paraplegia: A rare oncologic emergency case report in infancy and literature review.

    Posted 2018-06-17 10:00:42 by: Mahammad A. Tafida

    Related Articles Radiotherapy for Langerhans cell histiocytosis with paraplegia: A rare oncologic emergency case report in infancy and literature review. Brain Dev. 2018 Jun 12;: Authors: Nakashima K, Koga Y, Sakai Y, Takada H, Harimaya K, Ohga S, Taguchi T, Oda Y, Honda H, Ohga S Abstract BACKGROUND: Langerhans cell histiocytosis (LCH) is a clonal disease with focal or disseminated lesions that may compress the surrounding tissues, including the spinal cord. Because few reports have described the spinal symptoms as the first manifestation of pediatric LCH, the long-term neurological outcomes remain unclear. CASE REPORT AND LITERATURE REVIEW: We report a 21-month-old boy who presented with sudden-onset paraplegia. Imaging analyses revealed that osteolytic lesions and epidural tumors compressing the spinal cord at the T7-9 vertebrae. Twelve days after he developed leg weakness, emergency radiotherapy was started after a tumor biopsy. During the course of radiotherapy, paralysis steadily ameliorated. After we excluded infections and determined the pathological diagnosis of LCH, multi-drug chemotherapy was started. Apparent improvement in his complete paraplegia was observed after a total 15 Gy of radiotherapy and subsequent chemotherapy, leaving no neurological sequelae at 4 years of age. Through a literature search of studies published from 1980 to 2017, we found that children with LCH showed a generally favorable recovery from neurological dysfunction after the acute phase of spinal symptoms. CONCLUSION: This report underscores the utility of emergency radiotherapy for the neurological recovery of spinal LCH in infants. Our long-term observation further denotes the value of this treatment in terms of the intact survival with preserved motor functions and physical growth. PMID: 29907475 [PubMed - as supplied by ...

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  • Determinants and Prevention of Ventilator-Induced Lung Injury.

    Posted 2018-06-17 10:00:42 by: Mahammad A. Tafida

    Related Articles Determinants and Prevention of Ventilator-Induced Lung Injury. Crit Care Clin. 2018 Jul;34(3):343-356 Authors: Vasques F, Duscio E, Cipulli F, Romitti F, Quintel M, Gattinoni L Abstract Ventilator-induced lung injury develops from interactions between the lung parenchyma and applied mechanical power. In acute respiratory distress syndrome, the lung is smaller size with an inhomogeneous structure. The same mechanical force applied on a reduced parenchyma would produce volutrauma; the concentration of mechanical forces at inhomogeneous interfaces produces atelectrauma. Higher positive end-expiratory pressures favor volutrauma and reduce atelectrauma; lower values do the opposite. Volutrauma and atelectrauma harms and benefits, however, seem to be equivalent at 5 to 15 cm H2O. At values greater than 15 cm H2O, the risk of damage outweighs the benefits of major atelectrauma prevention. PMID: 29907269 [PubMed - in ...

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