Acute pulmonary embolism in a child with ANCA-negative Idiopathic Pulmonary Capillaritis

Diffuse alveolar hemorrhage is an uncommon and often fatal condition in children that is characterized by distinct histopathological etiologies. Herein, we discuss the case of an 11-year-old girl who presented with acute worsening of hypoxia and left-sided chest pain. The patient had lung biopsy-proven idiopathic pulmonary capillaritis and was being treated with prednisolone every alternate day, azathioprine, and hydroxychloroquine. A contrast-computed tomography (CT) scan of the chest showed an acute left lower-lobe pulmonary embolism. Negative results were obtained on a test for thrombophilia. In children, pulmonary embolism with anti-neutrophil cytoplasmic antibody-negative idiopathic pulmonary capillaritis is a rare clinical condition. The exact cause of thrombus formation in this case is unknown; however, obesity, immobility, and chronic systemic corticosteroid therapy probably played a role.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Antifungal Activity of Human Cathelicidin LL-37, a Membrane Disrupting Peptide, by Triggering Oxidative Stress and Cell Cycle Arrest in <i>Candida auris</i>

Candida auris, an evolving multidrug-resistant pathogenic yeast, is known for causing severe invasive infections associated with high mortality rates in hospitalized individuals. Distinct from other Candida species, C. auris can persist for longer periods on different surfaces and is resistant to all of the major classes of antifungal drugs. Therefore, there is an urgent need for new antimycotic drugs with improved efficacy and reduced toxicity. The development of new antifungals based on antimicrobial peptides from various sources is considered a promising alternative. In this study, we examined the in vitro anti-yeast activity of the human cathelicidin peptides LL-37 against clinical strains of C. auris alone and in combination with different antifungal drugs by broth microdilution assay. To understand the antifungal mechanism of action, cell envelopes, cell cycle arrest, and effect on oxidative stress enzymes were studied using standard protocols. The minimum inhibitory and fungicidal concentrations of cathelicidin LL-37 ranged from 25–100 and 50–200 µg/mL, respectively. A combination interaction in a 1:1 ratio (cathelicidin LL-37: antifungal drug) resulted in 70% synergy with fluconazole and 100% synergy with amphotericin B and caspofungin. Assessment of the C. auris membrane by using propidium iodide assay after exposure to cathelicidin LL-37 linked membrane permeabilization with inhibition of C. auris cell growth and viability. These results were backed up by scanning electron microscopy studies demonstrating that exposure with cathelicidin LL-37 caused C. auris cells to undergo extensive surface changes. Spectrophotometric analysis revealed that cathelicidin LL-37 caused oxidative stress in C. auris, as is evident from the significant increase in the activity of primary antioxidant enzymes. In addition, cathelicidin LL-37 inhibited the cell cycle and accumulated cells in the S phase. Therefore, these results specify the potential of cathelicidin LL-37 for developing a new and effective anti-Candida agent

Correction: Jamal et al. Preparation of 6-Mercaptopurine Loaded Liposomal Formulation for Enhanced Cytotoxic Response in Cancer Cells. <i>Nanomaterials</i> 2022, <i>12</i>, 4029

In the original publication [...

Curcumin Modulates Oxidative Stress, Fibrosis, and Apoptosis in Drug-Resistant Cancer Cell Lines

In cancer management, drug resistance remains a challenge that reduces the effectiveness of chemotherapy. Several studies have shown that curcumin resensitizes cancer cells to chemotherapeutic drugs to overcome resistance. In the present study, we investigate the potential therapeutic role of curcumin in regulating the proliferation of drug-resistant cancers. Six drug-sensitive (MCF7, HCT116, and A549) and -resistant (MCF7/TH, HCT116R, and A549/ADR) cancer cell lines were treated with curcumin followed by an analysis of cytotoxicity, LDH enzyme, total reactive oxygen species, antioxidant enzymes (SOD and CAT), fibrosis markers (TGF-β1 protein, fibronectin, and hydroxyproline), and expression of cellular apoptotic markers (Bcl-2, Bax, Bax/Bcl-2 ratio, Annexin V, cytochrome c, and caspase-8). Additionally, the expression of cellular SIRT1 was estimated by ELISA and RT-PCR analysis. Curcumin treatment at doses of 2.7–54.3 µM significantly reduced the growth of sensitive and resistant cells as supported with decreased viability and increased cellular LDH enzyme of treated cells compared to controls non-treated cells. Curcumin also at doses of 2.7 and 54.3 µM regulated the fibrogenesis by reducing the expression of fibrotic markers in treated cells. Analysis of apoptotic markers indicated increased Bax, Bax, Bax/Bcl-2 ratio, Annexin V, caspase-8, and cytochrome c expression, while Bcl-2 expressions were significantly reduced. In curcumin-treated cells at 2.7 μM, non-significant change in ROS with significant increase in SOD and CAT activity was observed, whereas an increase in ROS with a reduction in respective antioxidant enzymes were seen at higher concentrations along with significant upregulation of SIRT1. In conclusion, the present study shows that curcumin induces anticancer activity against resistant cancer cell lines in a concentration- and time-dependent manner. The protective activities of curcumin against the growth of cancer cells are mediated by modulating oxidative stress, regulating fibrosis, SIRT1 activation, and inducing cellular apoptosis. Therefore, curcumin could be tested as an auxiliary therapeutic agent to improve the prognosis in patients with resistant cancers

Preparation of 6-Mercaptopurine Loaded Liposomal Formulation for Enhanced Cytotoxic Response in Cancer Cells

6-Mercaptopurine (6-MP) is a well-known immunosuppressive medication with proven anti-proliferative activities. 6-MP possesses incomplete and highly variable oral absorption due to its poor water solubility, which might reduce its anti-cancer properties. To overcome these negative effects, we developed neutral and positively charged drug-loaded liposomal formulations utilizing the thin-film hydration technique. The prepared liposomal formulations were characterized for their size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The average size of the prepared liposomes was between 574.67 ± 37.29 and 660.47 ± 44.32 nm. Positively charged liposomes (F1 and F3) exhibited a lower PDI than the corresponding neutrally charged ones (F2 and F4). Entrapment efficiency was higher in the neutral liposomes when compared to the charged formulation. F1 showed the lowest IC50 against HepG2, HCT116, and MCF-7 cancer cells. HepG2 cells treated with F1 showed the highest level of inhibition of cell proliferation with no evidence of apoptosis. Cell cycle analysis showed an increase in the G1/G0 and S phases, along with a decrease in the G2/M phases in the cell lines treated with drug loaded positively charged liposomes when compared to free positive liposomes, indicating arrest of cells in the S phase due to the stoppage of priming and DNA synthesis outside the mitotic phase. As a result, liposomes could be considered as an effective drug delivery system for treatment of a variety of cancers; they provide a chance that a nanoformulation of 6-MP will boost the cytotoxicity of the drug in a small pharmacological dose which provides a dosage advantage

Physicians’ Characteristics Associated with Their Attitude to Family Presence during Adult Cardiopulmonary Resuscitation

Healthcare providers have disparate views of family presence during cardiopulmonary resuscitation; however, the attitudes of physicians have not been investigated systematically. This study investigates the patterns and determinants of physicians’ attitudes to FP during cardiopulmonary resuscitation in Saudi Arabia. A cross-sectional design was applied, where a sample of 1000 physicians was surveyed using a structured questionnaire. The study was conducted in the southern region of Saudi Arabia for over 11 months (February 2014–December 2014). The collected data was analyzed using the Pearson chi-square test. Spearman’s correlation analysis and chi-square test of independence were used for the analysis of physicians’ characteristics with their willingness to allow FP. 80% of physicians opposed FP during cardiopulmonary resuscitation. The majority of them believed that FP could lead to decreased bedside space, staff distraction, performance anxiety, interference with patient care, and breach of privacy. They also highlight FP to result in difficulty concerning stopping a futile cardiopulmonary resuscitation, psychological trauma to family members, professional stress among staff, and malpractice litigations. 77.9% mostly disagreed that FP could be useful in allaying family anxiety about the condition of the patient or removing their doubts about the care provided, improving family support and participation in patient care, or enhancing staff professionalism. Various concerns exist for FP during adult cardiopulmonary resuscitation, which must be catered when planning for FP execution

Clinical Presentation and Surgical Management of Five Pediatric Cases with Bronchogenic Cysts: Retrospective Case Series

Background: Bronchogenic cysts (BCs) refer to congenital lesions that result from primitive or abnormal foregut budding, and can be pulmonary or mediastinal. Their occurrence can take place at any point on the tracheobronchial tree, but they are usually localized in the lung parenchyma and mediastinum, and may be symptomatic or asymptomatic. Bronchogenic cyst symptoms can vary, depending on the size and location of the cyst. Methods: A retrospective review of the charts of five patients with a histopathological diagnosis of bronchogenic cysts was performed between 2014 and 2020. The patients reported in this study were diagnosed and managed at Abha Maternity and Children Hospital, Abha, southwest Saudi Arabia. In addition, demographic information, as well as diagnostic and therapeutic information, was provided for each patient, both at discharge and after discharge. All patients had confirmed congenital bronchogenic cysts with different clinical phenotypes and radiological findings. Results: All patients had histopathologically confirmed bronchogenic cysts with different clinical and radiological presentations. Two patients had mediastinal-located cysts; one had a laryngeal cyst; and the last two patients had infected intrapulmonary bronchogenic cysts. All patients underwent complete excision and did not experience recurrence or other postoperative complications during the follow-up period. The latter two patients required lobectomies of the right middle and upper lobes. Conclusions: Although bronchogenic cysts are considered a rare congenital pulmonary malformation, they should be considered in the differential diagnosis of pediatric patients with unusual airway and parenchymal lung manifestations, particularly, persistent stridor, feeding difficulty, and complicated pneumonia. Surgical excision of the cyst is the gold-standard therapy for symptomatic bronchogenic cysts and is highly recommended for asymptomatic ones. Long-term follow-up studies will be required to explore any long-term complications of BCs, particularly regarding the malignancy transformation