Location, location, location : Fibrin, cells, and fibrinolytic factors in thrombi

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Acute Hypoxic Respiratory Failure as a Complication of a Urinary Tract Infection During Pregnancy: A Case Presentation

Urinary tract infections (UTI), as well as asymptomatic bacteriuria, have the potential to cause serious morbidity during pregnancy making it imperative to identify and treat them promptly. If left untreated, a UTI can lead to pyelonephritis and sepsis. More importantly, UTIs are independently associated with intrauterine growth restriction (IUGR), premature rupture of membranes (PROM), preterm delivery, pulmonary edema, acute respiratory distress syndrome (ARDS), preeclampsia, and cesarean delivery. We report the case of NC, a 19 year old G1P0 at 36 weeks and 3 days GA who presented to the hospital with concern for rupture of membranes with associated back and abdominal pain. She was febrile to 100.3 and tachycardic on initial presentation. Her prenatal history was significant for recurrent E.coli bacteriuria and non-compliance with antibiotic therapy. The admitting resident was concerned for pyelonephritis and possible bacteremia so, the patient was started on broad spectrum antibiotics. She progressed in labor and delivered a healthy female via vacuum extraction for non-reassuring fetal heart tones. Subsequently, blood cultures came back positive for E.coli. Her postpartum course was complicated by elevated blood pressures and proteinuria with concerns for pre-eclampsia. She received appropriate treatment with magnesium sulfate and anti-hypertensive therapy. Her clinical picture worsened with the development of hypoxemia and pulmonary edema concerning for pre-eclampsia with severe features versus ARDS from her bacteremia. She improved with aggressive diuresis and was discharged home in stable condition. Acute pyelonephritis secondary to ongoing UTI affects 1-2% of women and has, in some cases, been shown to increase the risk of pulmonary edema. In contrast, acute pyelonephritis in non-pregnant women is rarely associated with ARDS. In this case it is almost impossible to know whether the pulmonary edema was a manifestation of preeclampsia or ARDS from the UTI or a combination of both. Nonetheless, this case serves as a reminder of the importance of treating asymptomatic bacteriuria in pregnancy and the potential sequela including preterm delivery, ARDS and preeclampsia. It is important that we, as physicians, continue to educate our patients about the importance of treating asymptomatic bacteriuria and UTIs in pregnancy given the morbidity associated with it

Critical limit of copper in soil and plant for predicting response of oat (Avena sativa) in soils of Haryana

In order to evaluate critical level in oat (Avena sativa L.), laboratory and a screen house experiment was conducted at CCS HAU, Hisar. Bulk surface soil samples (0-15 cm) were collected from eighteen (18) different locations, in the state representing major soil groups of Haryana. The results of the study revealed that the relationship between Bray's per cent yield against DTPA-Cu in soil and Cu concentration in plants indicated critical deficiency level of Cu in soil as 0.30 mg/kgand for oat plant it was 11.7 mg/kg which was statistically also at par

Location, location, location: Fibrin, cells, and fibrinolytic factors in thrombi

Thrombi are heterogenous in nature with composition and structure being dictated by the site of formation, initiating stimuli, shear stress, and cellular influences. Arterial thrombi are historically associated with high platelet content and more tightly packed fibrin, reflecting the shear stress in these vessels. In contrast, venous thrombi are generally erythrocyte and fibrin-rich with reduced platelet contribution. However, these conventional views on the composition of thrombi in divergent vascular beds have shifted in recent years, largely due to recent advances in thromboectomy and high-resolution imaging. Interestingly, the distribution of fibrinolytic proteins within thrombi is directly influenced by the cellular composition and vascular bed. This in turn influences the susceptibility of thrombi to proteolytic degradation. Our current knowledge of thrombus composition and its impact on resistance to thrombolytic therapy and success of thrombectomy is advancing, but nonetheless in its infancy. We require a deeper understanding of thrombus architecture and the downstream influence on fibrinolytic susceptibility. Ultimately, this will aid in a stratified and targeted approach to tailored antithrombotic strategies in patients with various thromboembolic diseases

Fibrinogenolysis and fibrinolysis in Vaccine-induced Immune Thrombocytopenia and Thrombosis (VITT)

Acknowledgements The authors would like to thank all the patients whose samples were used as part of this study, and all the NHS Scotland staff who collected patient samples and looked after these patients. We thank Aberdeen Royal Infirmary Haematology laboratory for conducting the anti-platelet factor 4 antibody testing and Dr Sue Pavord, Consultant Haematologist at Oxford Teaching Hospitals for help in gathering clinical data on the patients. Funding This research was supported by The University of Aberdeen Development Trust (RG16009). CSW and NJM are supported by the British Heart Foundation (PG/15/82/31721; PG/20/17/35050).Peer reviewedPublisher PD

Stability indicating method development and validation for simultaneous estimation of atorvastatin calcium and celecoxib in bulk and niosomal formulation by RP-HPLC

The present work describes development and validation of a specific, sensitive, precise and stability-indicating high-performance liquid chromatographic method of analysis of atorvastatin calcium and celecoxib, both as a bulk drug and in niosomal formulation. The analysis has been performed by using Cosmosil-C18 column (4.6 mm´250 mm, 5 m) at 25 °C using acetonitrile: ammonium acetate buffer pH 5.0: methanol (50:25:25 v/v/v) as mobile phase. The detection was carried out at 277nm with a flow rate of 1.0mL/min. The retention times of Atorvastatin calcium and Celecoxib were 6.195 and 3.989min, respectively. The method was validated according to ICH guidelines, for specificity, precision, linearity, accuracy and robustness. Atorvastatin calcium and Celecoxib were subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The degradation was observed in oxidation and acid hydrolysis. The linearity for atorvastatin calcium and celecoxib were in the range of 100-500 µg/mL. The recovery study of atorvastatin and celecoxib were found to be in the range of 98.96 - 99.92% and 98.90-100%, respectively. The proposed method was validated and successfully applied to the estimation of Atorvastatin calcium and Celecoxib in combined in-house niosomal formulation.O presente trabalho descreve o desenvolvimento e a validação de método de análise por cromatografia de alta eficiência específico, sensível, preciso e indicador de estabilidade de atorvastatina cálcica e celecoxibe, ambos como fármaco e como formulação niosômica. A análise foi realizada utilizando coluna Cosmosil-C18 (4,6 mm´250 mm, 5 m) a 25 °C, e acetonitrila: tampão acetato de amônio pH 5,0: metanol (50:25:25 v/v/v) como fase móvel. A detecção foi realizada a 277 nm, com fluxo de 1,0 mL/min. Os tempos de retenção de atorvastatina cálcica e de celecoxibe foram 6,195 e 3,989 min, respectivamente. O método foi validado de acordo com as regras da ICH para especificidade, precisão, exatidão e robustez. A atorvastatina cálcica e o celecoxibe foram submetidos a condições de estresse por hidrólise, oxidação, fotólise e degradação térmica. A degradação foi observada por oxidação e hidrólise ácida. Observou-se a linearidade da atorvastatina cálcica e do celecoxibe na faixa de 100-500 µg/mL. A recuperação da atorvastatina e do celecoxibe foi observada na faixa de 98,96-99,92% e 98,90-100%, respectivamente. O método proposto foi validado e aplicado com sucesso para a determinação de atorvastatina cálcica e celecoxibe em formulação niosômica caseira combinada

Identification of SARS-CoV-2 inhibitors targeting Mpro and PLpro using in-cell-protease assay

SARS-CoV-2 proteases Mpro and PLpro are promising targets for antiviral drug development. In this study, we present an antiviral screening strategy involving a novel in-cell protease assay, antiviral and biochemical activity assessments, as well as structural determinations for rapid identification of protease inhibitors with low cytotoxicity. We identified eight compounds with anti-SARS-CoV-2 activity from a library of 64 repurposed drugs and modeled at protease active sites by in silico docking. We demonstrate that Sitagliptin and Daclatasvir inhibit PLpro, and MG-101, Lycorine HCl, and Nelfinavir mesylate inhibit Mpro of SARS-CoV-2. The X-ray crystal structure of Mpro in complex with MG-101 shows a covalent bond formation between the inhibitor and the active site Cys145 residue indicating its mechanism of inhibition is by blocking the substrate binding at the active site. Thus, we provide methods for rapid and effective screening and development of inhibitors for blocking virus polyprotein processing as SARS-CoV-2 antivirals. Additionally, we show that the combined inhibition of Mpro and PLpro is more effective in inhibiting SARS-CoV-2 and the delta variant

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr