Late histological findings in symptomatic COVID-19 patients: A case report

RATIONALE: Although there have been several studies describing clinical and radiographic features about the novel coronavirus (COVID-19) infection, there is a lack of pathologic data conducted on biopsies or autopsies. PATIENT CONCERNS: A 56-year-old and a 70-year-old men with fever, cough, and respiratory fatigue were admitted to the intensive care unit and intubated for respiratory distress. DIAGNOSIS: The nasopharyngeal swab was positive for COVID-19 and the chest Computed Tomography (CT) scan showed the presence of peripheral and bilateral ground-glass opacities. INTERVENTIONS: Both patients developed pneumothoraces after intubation and was managed with chest tube. Due to persistent air leak, thoracoscopies with blebs resection and pleurectomies were performed on 23rd and 16th days from symptoms onset. OUTCOMES: The procedures were successful with no evidence of postoperative air-leak, with respiratory improvement. Pathological specimens were analyzed with evidence of diffuse alveolar septum disruption, interstitium thickness, and infiltration of inflammatory cells with diffuse endothelial dysfunction and hemorrhagic thrombosis. LESSONS: Despite well-known pulmonary damages induced by the COVID-19, the late-phase histological changes include diffused peripheral vessels endothelial hyperplasia, in toto muscular wall thickening, and intravascular hemorrhagic thrombosis

Anticancer effects against colorectal cancer models of chloro(triethylphosphine)gold(I) encapsulated in PLGA–PEG nanoparticles

Chloro(triethylphosphine)gold(I), (Et(3)PAuCl hereafter), is an Auranofin (AF)-related compound showing very similar biological and pharmacological properties. Like AF, Et(3)PAuCl exhibits potent antiproliferative properties in vitro toward a variety of cancer cell lines and is a promising anticancer drug candidate. We wondered whether Et(3)PAuCl encapsulation might lead to an improved pharmacological profile also considering the likely reduction of unwanted side-reactions that are responsible for adverse effects and for drug inactivation. Et(3)PAuCl was encapsulated in biocompatible PLGA–PEG nanoparticles (NPs) and the new formulation evaluated in colorectal HCT-116 cancer cells in comparison to the free gold complex. Notably, encapsulated Et(3)PAuCl (nano-Et(3)PAuCl hereafter) mostly retains the cellular properties of the free gold complex and elicits even greater cytotoxic effects in colorectal cancer (CRC) cells, mediated by apoptosis and autophagy. Moreover, a remarkable inhibition of two crucial signaling pathways, i.e. ERK and AKT, by nano-Et(3)PAuCl, was clearly documented. The implications of these findings are discussed. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10534-021-00313-0

Use of an Abdominal Compression Device in Colonoscopy: A Randomized, Sham-Controlled Trial

Looping is a common problem during colonoscopy that prolongs procedure time. We aimed to determine the efficacy and safety of ColoWrap, an external abdominal compression device, with respect to insertion time and other procedural outcomes

Advanced Technologies for Oral Controlled Release: Cyclodextrins for oral controlled release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug-drug or drug-additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g. as osmotic pumps) and/ or hydrophobic CDs. New controlled delivery systems based on nanotechonology carriers (nanoparticles and conjugates) have also been reviewed

Effects of immunomodulatory drugs on TNF-α and IL-12 production by purified epidermal langerhans cells and peritoneal macrophages

<p>Abstract</p> <p>Background</p> <p>Langerhans cells constitute a special subset of immature dendritic cells localized in the epidermis that play a key role in the skin's immune response. The production of cytokines is a key event in both the initiation and the regulation of immune responses, and different drugs can be used to remove or modify their production by DC and, therefore, alter immune responses in a broad spectrum of diseases, mainly in human inflammatory and autoimmune diseases. In the present study, we examined the effects of prednisone, thalidomide, cyclosporine A, and amitriptyline, drugs used in a variety of clinical conditions, on the production of TNF-α, IL-10, and IL-12 by purified epidermal Langerhans cells and peritoneal macrophages in BALB/c mice.</p> <p>Findings</p> <p>All drugs inhibited TNF-α production by Langerhans cells after 36 hours of treatment at two different concentrations, while prednisone and thalidomide decreased IL-12 secretion significantly, amitriptyline caused a less pronounced reduction and cyclosporine A had no effect. Additionally, TNF-α and IL-12 production by macrophages decreased, but IL-10 levels were unchanged after all treatments.</p> <p>Conclusions</p> <p>Our results demonstrate that these drugs modulate the immune response by regulating pro-inflammatory cytokine production by purified epidermal Langerhans cells and peritoneal macrophages, indicating that these cells are important targets for immunosuppression in various clinical settings.</p

Tissue hyaluronan expression, as reflected in the sputum of lung cancer patients, is an indicator of malignancy

Hyaluronan (HA) shows promise for detecting cancerous change in pleural effusion and urine. However, there is uncertainty about the localization of HA in tumor tissue and its relationship with different histological types and other components of the extracellular matrix, such as angiogenesis. We evaluated the association between HA and degree of malignancy through expression in lung tumor tissue and sputum. Tumoral tissue had significantly increased HA compared to normal tissue. Strong HA staining intensity associated with cancer cells was significant in squamous cell carcinoma compared to adenocarcinoma and large cell carcinoma. A significant direct association was found between tumors with a high percentage of HA and MVD (microvessel density) in tumoral stroma. Similarly significant was the direct association between N1 tumors and high levels of HA in cancer cells. Cox multivariate analysis showed significant association between better survival and low HA. HA increased in sputum from lung cancer patients compared to cancer-free and healthy volunteers and a significant correlation was found between HA in sputum and HA in cancer tissue. Localization of HA in tumor tissue was related to malignancy and reflected in sputum, making this an emerging factor for an important diagnostic procedure in patients suspected to have lung cancer. Further study in additional patients in a randomized prospective trial is required to finalize these results and to validate our quantitative assessment of HA, as well as to couple it to gold standard sputum cytology.Research supported by FAPESP (2010/11005-5 and 2010/04462) and CNPq (#471939/2010-2 and 483005/2012-6

Cooperation among cancer cells: applying game theory to cancer

Cell cooperation promotes many of the hallmarks of cancer via the secretion of diffusible factors that can affect cancer cells or stromal cells in the tumour microenvironment. This cooperation cannot be explained simply as the collective action of cells for the benefit of the tumour because non-cooperative subclones can constantly invade and free-ride on the diffusible factors produced by the cooperative cells. A full understanding of cooperation among the cells of a tumour requires methods and concepts from evolutionary game theory, which has been used successfully in other areas of biology to understand similar problems but has been underutilized in cancer research. Game theory can provide insights into the stability of cooperation among cells in a tumour and into the design of potentially evolution-proof therapies that disrupt this cooperation