1 The possible role of cyclic AMP phosphodiesterase (PDE) in the inhibitory actions of ibudilast on tracheal smooth muscle contractility and eosinophil thromboxane generation was investigated. 2 Ibudilast was a non-selective inhibitor of partially purified cyclic nucleotide PDE isoenzymes from pig aorta and bovine tracheal smooth muscle, exhibiting only moderate potency against bovine tracheal PDE IV (IC0 = 12 ± 4 AM, n = 3). Similar or slightly lower potencies were displayed against PDEs I, II, III and V. In contrast, rolipram exhibited selectivity for PDE IV (3 0.5 AM, n = 3).3 Ibudilast (IC50 = 0.87 ± 0.37 AM, n = 3), like rolipram (IC = 0.20 0.04 AM, n = 3), was a more potent inhibitor of membrane-bound PDE IV from guinea-pig eosinophils than of partially purified PDE IV from bovine tracheal smooth muscle. The potency of ibudilast increased when the eosinophil enzyme was solubilised with deoxycholate and NaCl (IC50 = 0.11 ± 0.05 JAM, n = 3) or exposed to vanadate/glutathione complex (V/GSH) (ICo=0.11 ± 0.02 JM, n = 3). The potency of rolipram was also increased by solubilization (IC50 = 0.012 0.003, n = 3) or V/GSH (IC,0 = 0.012 ± 0.003, n = 3). 4 In intact eosinophils, ibudilast (0.032 jiM-20 JM) potentiated isoprenaline-induced cyclic AMP accumulation in a concentration-dependent manner, being approximately 20 fold less potent than rolipram. Little or no effect on basal cyclic AMP levels was observed with either compound. The cyclic AMP-dependent protein kinase activity ratio was significantly increased following incubation of eosinophils with either ibudilast (20 AM) or rolipram (20 gM) in the absence or presence of isoprenaline. 5Leukotriene B4 (300 nM)-induced thromboxane generation from guinea-pig eosinophils was inhibited by ibudilast (IC50 = 11.3 ± 3.7 AM, n = 5) and rolipram (IC,0 = 0.280 ± 0.067 AM, n = 5) in a concentration-dependent manner. 6 Ibudilast (10 nM-I AM), whilst generally less potent than rolipram (1 nM-AM), produced concentration-dependent relaxation of spasmogen (methacholine, histamine, LTD4)-induced tone in the guineapig isolated tracheal strip. Ibudilast was less potent in reversing the methacholine (IC50 = 1.95 ± 0.40 JM, n = 6)-induced contraction than those of histamine (IC50 = 0.18 ± 0.70 AM, n =6) or leukotriene D4 (LTD4, IC50 = 0.12 ± 0.05 JM, n = 6). Rolipram also exhibited a similar pattern of activity, although the difference in potency against methacholine (IC50 = 0.1 ± 0.01 JAM, n = 6) compared with the other two spasmogens, histamine (IC50 = 0.034 ± 0.017 JM, n = 7) and LTD4 (IC50 = 0.026 ± 0.008 AM, n = 7), was not as great.7 These results demonstrate that ibudilast, like rolipram, has several biological actions on the eosinophil and airways smooth muscle which may be attributed to inhibition of cyclic AMP PDE. These actions may account, at least in part, for the recently reported anti-asthma effects of ibudilast.
Mucormycosis, a deadly fungal infection, has affected thousands of COVID-19 patients in India. Mucormycosis, formerly known as zygomycosis, is caused by the many fungi that belong to the family “Mucorales.” These molds are commonly found in soil, air, and damp walls and frequently colonize oral mucosa, nose, paranasal sinuses, and throat. The pathophysiological consequences of diabetes combined with the acute inflammatory surge in COVID-19 and steroid treatment weakens person’s immunity and renders susceptibility to fungal infections. Patients treated for severe COVID-19 have damaged lungs and suppressed immune system, an environment that supports fungal infection. Fungal spores can grow in airways or sinuses, and invade bodies’ tissues, explaining why the nasal cavity and paranasal sinuses are the most common site of mucormycosis infection, the consequential spread to the eyes can cause blindness, or causing headaches or seizures if the infection spreads to the brain. Poorly controlled diabetes often results in acidosis in tissues a suitable environment for Mucorales fungi to grow, exacerbating the risk for mucormycosis. This becomes clinically important, especially in India that has an increased prevalence of undiagnosed and uncontrolled diabetes. Given that a significant increase in the cases of mucormycosis in the diabetic patients treated for COVID-19 is strongly associated with corticosteroid administration, there is a need to evaluate use of dietary nutraceuticals with immune boosting potentials that modulate metabolic abnormalities in the management of COVID-19 associated mucormycosis.
Background: During the coronavirus disease 2019 (COVID-19) pandemic, internet-based learning modalities and online classes became a tool for the continuous learning process for medical students. The aim of this study was to compare medical student performance in both online versus offline instructional methods. Methods: The study was conducted on 213 medical students of the basic science program at the American University of Antigua, College of Medicine (AUACOM), who completed the four semesters consecutively between Spring 2018 and Fall 2020. Two cohorts of students were considered in the study: cohort 1 (those who completed years 1 and 2 using traditional offline teaching modality) and cohort 2 (those who completed year 1 offline and year 2 online). The years 1 and 2 National Board of Medical Examiners (NBME) summative assessment scores of the students were used to determine which instructional modality generated better student performance outcomes for the two groups. Additionally, we evaluated the score variabilities between genders to determine if teaching modality had an impact on a specific group. All statistical comparisons were done using two-tailed t -tests. Results: The study involves 213 students (112 in cohort 1, 101 in cohort 2). There was no significant difference in student performance between offline and online learners overall (74 ± 2.3 vs. 73 ± 1.3; p = 0.537) or with respect to gender (73 ± 3.8 vs. 73 ± 3.0; p = 0.709). Conclusion: In this comparative effectiveness study of traditional offline education versus online instructional modality, we observed no statistical difference in student performance evaluated with NBME summative assessment scores. Online classes were well-accepted by our students. These data show a significant and promising potential for the future of medical education using online teaching modalities. Remote online teaching could be used again in the future without detriment to student education if face-to-face (F2F) learning is not possible.
Medical students are prone to anxiety and depression, largely due to the nature of their coursework. During the COVID-19 pandemic, many medical students were required to study from home without being involved in clinical practice. The aim of this study was to investigate depression and generalized anxiety disorder (GAD), plus possible risk factors in medical students around the world during the pandemic. A primary search was conducted using PubMed, limited to the period 2020–2021. A second search was conducted to acquire studies published before the pandemic, aiming to have a baseline prevalence value for these disorders in medical students. During the pandemic, the prevalence of depression in the USA (31.7%, 12.5%, and 10.8% for mild, moderate, and severe depression, respectively) was higher than the reported prevalence in Pakistan, Nepal, and Iran, although the four countries used different psychiatric instruments, making comparison difficult (9-item Patient Health Questionnaire, Self-rating Depression Scale, Hospital Anxiety and Depression Scale-Depression [HADS-D], and Beck Depression Inventory [BDI-II). The prevalence of GAD in the USA was also higher (35.3%, 19.5%, and 11.1%, for mild, moderate, and severe GAD) than the prevalence in China (21.3%, 2.7%, and 0.9%, for mild, moderate, and severe anxiety), and the overall prevalence in Brazil, (46.2%), using the same instrument (GAD-7). The prevalence of GAD in the USA was also higher than the prevalence in Nepal, Pakistan, and Iran, although the researchers used a different psychiatric instrument (HADS-A, Self-rating Anxiety Scale, and Beck Anxiety Inventory instruments, respectively). Before the pandemic, the reported prevalence of depression in the USA was lower (11.6%, 9.0%, and 3.0% for mild, moderate, and severe depression), than in Pakistan (31.0%, 13.6%, and 4.8%), using the BDI instrument. In Nepal, the prevalence of depression (5.2%) was higher than in Portugal (2.3%), ascertained with the HADS-D instrument. The prevalence in Egypt (65% using Depression Anxiety Stress Scale DASS-21]) and India (14.7%, 19%, and 17.5% mild, moderate, and severe depression, using DASS 42) were the highest prevalence values reported before the pandemic. For anxiety, the prevalence of overall GAD in Nepal (16.2%) was comparable to the one reported in Portugal (14.2%), both identified with the HADS-A instrument. The prevalence of GAD reported in India and in Egypt were the highest values, determined with the DASS 42 and DASS 21, respectively. Studies have reported that general social isolation and loneliness are risk factors contributing factors toward depression. Other risk factors identified with depression and/or anxiety disorders were being female, having a lower GPA, lower COVID-19 awareness, and having more experience with COVID symptoms. High prevalence of depression and GAD was identified in medical students in various countries. It is imperative that during any crisis such as the one experienced in the present COVID-19 pandemic, vulnerable populations to mental health disorders, such as medical students, are identified and supported. Further research needs to be done to explore other possible factors, such as living conditions, marital status, social-cultural influences, financial issues, and their relationship to depression and anxiety in this population, to further understand the best interventions to support this population.
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