Polycationic Glycosides

Cationic lipids have long been known to serve as antibacterial and antifungal agents. Prior efforts with attachment of cationic lipids to carbohydrate-based surfaces have suggested the possibility that carbohydrate-attached cationic lipids might serve as antibacterial and antifungal pharmaceutical agents. Toward the understanding of this possibility, we have synthesized several series of cationic lipids attached to a variety of glycosides with the intent of generating antimicrobial agents that would meet the requirement for serving as a pharmaceutical agent, specifically that the agent be effective at a very low concentration as well as being biodegradable within the organism being treated. The initial results of our approach to this goal are presented

COVID-19 on Chest CT: Translating Known Microscopic Findings to Imaging Observations

Purpose: To describe the imaging findings of COVID-19 and correlate them with their known pathology observations. Methods: This is an IRB-approved retrospective study performed at Columbia University Irving Medical Center (IRB # AAAS9652) that included symptomatic adult patients (21 years or older) who presented to our emergency room and tested positive for COVID-19 and were either admitted or discharged with at least one chest CT from 11 March 2020 through 1 July 2020. CT scans were ordered by the physicians caring for the patients; our COVID-19 care protocols did not specify the timing for chest CT scans. A scoring system was used to document the extent of pulmonary involvement. The total CT grade was the sum of the individual lobar grades and ranged from 0 (no involvement) to 16 (maximum involvement). The distribution of lung abnormalities was described as peripheral (involving the outer one-third of the lung), central (inner two-thirds of the lung), or both. Additional CT findings, including the presence of pleural fluid, atelectasis, fibrosis, cysts, and pneumothorax, were recorded. Contrast-enhanced CT scans were evaluated for the presence of a pulmonary embolism, while non-contrast chest CT scans were evaluated for hyperdense vessels. Results: 209 patients with 232 CT scans met the inclusion criteria. The average age was 61 years (range 23–97 years), and 56% of the patients were male. The average score reflecting the extent of the disease on the CT was 10.2 (out of a potential grade of 16). Further, 73% of the patients received contrast, which allowed the identification of a pulmonary embolism in 21%. Of those without contrast, 33% had hyperdense vessels, which might suggest a chronic pulmonary embolism. Further, 47% had peripheral opacities and 9% had a Hampton’s hump, and 78% of the patients had central consolidation, while 28% had round consolidations. Atelectasis was, overall, infrequent at 5%. Fibrosis was observed in 11% of those studied, with 6% having cysts and 3% pneumothorax. Conclusions: The CT manifestations of COVID-19 can be divided into findings related to endothelial and epithelial injury, as were seen on prior post-mortem reports. Endothelial injury may benefit from treatments to stabilize the endothelium. Epithelial injury is more prone to developing pulmonary fibrotic changes

A clinically relevant model of acute respiratory distress syndrome in human-size swine

Despite over 30 years of intensive research for targeted therapies, treatment of acute respiratory distress syndrome (ARDS) remains supportive in nature. With mortality upwards of 30%, a high-fidelity pre-clinical model of ARDS, on which to test novel therapeutics, is urgently needed. We used the Yorkshire breed of swine to induce a reproducible model of ARDS in human-sized swine to allow the study of new therapeutics, from both mechanistic and clinical standpoints. For this, animals were anesthetized, intubated and mechanically ventilated, and pH-standardized gastric contents were delivered bronchoscopically, followed by intravenous infusion of Escherichia coli-derived lipopolysaccharide. Once the ratio of arterial oxygen partial pressure (PaO(2)) to fractional inspired oxygen (F(I)O(2)) had decreased to <150, the animals received standard ARDS treatment for up to 48 h. All swine developed moderate to severe ARDS. Chest radiographs taken at regular intervals showed significantly worse lung edema after induction of ARDS. Quantitative scoring of lung injury demonstrated time-dependent increases in interstitial and alveolar edema, neutrophil infiltration, and mild to moderate alveolar membrane thickening. This pre-clinical model of ARDS in human-sized swine recapitulates the clinical, radiographic and histopathologic manifestations of ARDS, providing a tool to study therapies for this highly morbid lung disease

Polycationic Glycosides

Cationic lipids have long been known to serve as antibacterial and antifungal agents. Prior efforts with attachment of cationic lipids to carbohydrate-based surfaces have suggested the possibility that carbohydrate-attached cationic lipids might serve as antibacterial and antifungal pharmaceutical agents. Toward the understanding of this possibility, we have synthesized several series of cationic lipids attached to a variety of glycosides with the intent of generating antimicrobial agents that would meet the requirement for serving as a pharmaceutical agent, specifically that the agent be effective at a very low concentration as well as being biodegradable within the organism being treated. The initial results of our approach to this goal are presented

Preclinical evidence for the role of stem/stromal cells in COPD

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide and there are currently limited treatment options for these patients. The disease is characterized by a reduction in airflow due to chronic bronchitis, as well as airspace enlargement in the distal lung, resulting in a loss of surface area available for gas exchange. At end-stage disease, oxygen therapy and lung transplantation remain the only potential options. The disease is heterogeneous and both inflammatory cells as well as structural cells are thought to play a role in disease onset and progression. Pharmaceutical approaches are ineffective at reversing disease pathology and currently aim only to provide symptomatic relief. A recent area of investigation focuses on exogenous cell therapy, including stem cell administration, and its potential for directing lung regeneration. Cell therapies from a variety of sources, as well as cell-derived products such as extracellular vesicles, have recently shown efficacy in animal models of COPD, but early clinical trials have not yet shown efficacy. In this chapter, we discuss the different animal models of COPD as well as the studies which have been conducted to date with cell therapies. We conclude the chapter with a discussion regarding the limitations of current animal models and discuss potential areas for future study