scholarly journals Deficient synthesis of melatonin in COVID-19 can impair the resistance of coronavirus patients to mucormycosis

2021 ◽  
Author(s):  
Amarnath Sen
Keyword(s):  
Selective Serotonin Reuptake Inhibitors ◽  
Iron Acquisition ◽  
Iron Chelator ◽  
Melatonin Level ◽  
Diabetic Patients ◽  
Fungal Virulence ◽  
Angiotensin Converting Enzyme 2 ◽  
Cell Immunity ◽  
Uncontrolled Diabetes ◽  
Glucose Regulated Protein

Though it is thought that uncontrolled diabetes and the excessive use of corticosteroids are responsible for COVID-19 associated mucormycosis (CAM), researchers are on the lookout for additional reasons to explain the recent spurt of CAM in India. In the present paper it is argued that melatonin deficiency in COVID-19 plays a major role in CAM. Incidentally, melatonin is synthesized from tryptophan via the serotonin pathway and melatonin deficiency in COVID-19 arises from the faulty absorption of tryptophan from the food because SARS-COV-2 downregulates angiotensin-converting enzyme-2, which is the chaperone of the transporter of tryptophan, a key component in the process of uptake of tryptophan. The melatonin deficiency enhances the fungal virulence by facilitating iron acquisition and by promoting morphological transition of the mucor species from the yeast to the virulent hyphal form. Additionally, melatonin deficiency aggravates the suppression of T-cell immunity in the patients receiving steroids. Hence, the restoration of melatonin level should resolve the issues and help in defeating CAM, given the fact that melatonin is an iron chelator, inhibitor of myeloperoxidase, inhibitor of ferroptosis and pyroptosis and calmodulin blocker. Also, by lowering the expression of glucose-regulated protein-78, melatonin can further increase the resistance of diabetic patients to mucormycosis. Hence, clinical trials should be carried out to ascertain how tryptophan supplementation, administration of selective serotonin reuptake inhibitors (to increase serotonin, the precursor of melatonin), and exogenous melatonin help in correcting the melatonin deficiency and eliminating or reducing the propensity of the patients to CAM.

"Taming the Monster aka Uncontrolled Diabetes: A Viewpoint" (Preprint)

2020 ◽  
Author(s):  
Swati Anand ◽  
Amardeep Kalsi ◽  
Jonathan Figueroa ◽  
Parag Mehta
Keyword(s):  
Blood Glucose ◽  
Diabetes Management ◽  
Positive Impact ◽  
The United States ◽  
Phone Call ◽  
Diabetic Patients ◽  
Dietary Compliance ◽  
Glucose Levels ◽  
Uncontrolled Diabetes ◽  
Number Of Patients

BACKGROUND HbA1c between 6% and 6.9% is associated with the lowest incidence of all‐cause and CVD mortality, with a stepwise increase in all‐cause and cardiovascular mortality in those with an HbA1c >7%. • There are 30 million individuals in the United States (9.4% of the population) currently living with Diabetes Mellitus. OBJECTIVE Improving HbA1C levels in patients with uncontrolled Diabetes with a focused and collaborative effort. METHODS Our baseline data for Diabetic patients attending the outpatient department from July 2018 to July 2019 in a University-affiliated hospital showed a total of 217 patients for one physician. • Of 217 patients, 17 had HbA1C 9 and above. We contacted these patients and discussed the need for tight control of their blood glucose levels. We intended to ensure them that we care and encourage them to participate in our efforts to improve their outcome. • We referred 13 patients that agreed to participate to the Diabetic educator who would schedule an appointment with the patients, discuss their diet, exercise, how to take medications, self-monitoring, and psychosocial factors. • If needed, she would refer them to the Nutritionist based on patients’ dietary compliance. • The patients were followed up in the next two weeks via telemedicine or a phone call by the PCP to confirm and reinforce the education provided by the diabetes educator. RESULTS Number of patients that showed an improvement in HbA1C values: 11 Cumulative decrease in HbA1C values for 13 patients: 25.3 The average reduction in HbA1C: 1.94 CONCLUSIONS Our initiative to exclusively target the blood glucose level with our multidisciplinary approach has made a positive impact, which is reflected in the outcome. • It leads to an improvement in patient compliance and facilitates diabetes management to reduce the risk for complications CLINICALTRIAL NA

scholarly journals When Uncontrolled Diabetes Mellitus and Severe COVID-19 Converge: The Perfect Storm for Mucormycosis

2021 ◽  
Vol 7 (4) ◽  
pp. 298
Author(s):  
Teny M. John ◽  
Ceena N. Jacob ◽  
Dimitrios P. Kontoyiannis
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Clinical Features ◽  
The Other ◽  
Diabetic Patients ◽  
Epidemiological Factors ◽  
Uncontrolled Diabetes ◽  
Diagnostic Certainty ◽  
Patients With Diabetes ◽  
Perfect Storm

Mucormycosis (MCR) has been increasingly described in patients with coronavirus disease 2019 (COVID-19) but the epidemiological factors, presentation, diagnostic certainty, and outcome of such patients are not well described. We review the published COVID-19-associated mucormycosis (CAMCR) cases (total 41) to identify risk factors, clinical features, and outcomes. CAMCR was typically seen in patients with diabetes mellitus (DM) (94%) especially the ones with poorly controlled DM (67%) and severe or critical COVID-19 (95%). Its presentation was typical of MCR seen in diabetic patients (mostly rhino-orbital and rhino-orbital-cerebral presentation). In sharp contrast to reported COVID-associated aspergillosis (CAPA) cases, nearly all CAMCR infections were proven (93%). Treating physicians should have a high suspicion for CAMCR in patients with uncontrolled diabetes mellitus and severe COVID-19 presenting with rhino-orbital or rhino-cerebral syndromes. CAMR is the convergence of two storms, one of DM and the other of COVID-19.

scholarly journals Type-2 Diabetes as a Risk Factor for Severe COVID-19 Infection

2021 ◽  
Vol 9 (6) ◽  
pp. 1211
Author(s):  
Mahnaz Norouzi ◽  
Shaghayegh Norouzi ◽  
Alistaire Ruggiero ◽  
Mohammad S. Khan ◽  
Stephen Myers ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Factor ◽  
Inflammatory Responses ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Diabetic Patients ◽  
Angiotensin Converting Enzyme 2 ◽  
Immune System Dysfunction ◽  
Current Outbreak

The current outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed coronavirus disease 2019 (COVID-19), has generated a notable challenge for diabetic patients. Overall, people with diabetes have a higher risk of developing different infectious diseases and demonstrate increased mortality. Type 2 diabetes mellitus (T2DM) is a significant risk factor for COVID-19 progression and its severity, poor prognosis, and increased mortality. How diabetes contributes to COVID-19 severity is unclear; however, it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Using the envelope spike glycoprotein SARS-CoV-2, COVID-19 binds to angiotensin-converting enzyme 2 (ACE2) receptors, a key protein expressed in metabolic organs and tissues such as pancreatic islets. Therefore, it has been suggested that diabetic patients are more susceptible to severe SARS-CoV-2 infections, as glucose metabolism impairments complicate the pathophysiology of COVID-19 disease in these patients. In this review, we provide insight into the COVID-19 disease complications relevant to diabetes and try to focus on the present data and growing concepts surrounding SARS-CoV-2 infections in T2DM patients.

Abstract 657: Increased Urinary Angiotensin Converting Enzyme 2 (ACE2) In Type 2 Diabetic Patients

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Sridevi Gutta ◽  
Nadja Grobe ◽  
Hassan Osman ◽  
Mohammad Saklayen ◽  
Khalid M Elased
Keyword(s):  
Mass Spectrometry ◽  
Medical Center ◽  
Diabetic Patients ◽  
Enzyme Assays ◽  
Renal Tubules ◽  
Type 2 Diabetic Patients ◽  
Major Health ◽  
Angiotensin Converting Enzyme 2 ◽  
Noninvasive Biomarker

Diabetes and its associated chronic kidney disease (CKD) is a major health burden and there is an urgent need for new sensitive biomarkers to detect and monitor the progression of CKD. Albuminuria is still the gold standard for the evaluation of kidney function. However, its sensitivity and reliability have recently been questioned. ACE2 is highly expressed in renal tubules and has been shown to be shed in the urine of diabetic patients with CKD. The aim of the study was to investigate whether urinary ACE2 is increased in diabetic patients with CKD before the onset of microalbuminuria. Participants were recruited from Dayton VA Medical Center (Dayton, OH, USA). Baseline urinary albumin creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) were determined three months before initiation of the study in non-diabetic patients (UACR <30 mg/g, eGFR=97.40±16 ml/min/1.73 m 2 ), and in diabetic patients with normoalbuminuria (UACR <30 mg/g, eGFR=83.08±17 ml/min/1.73 m 2 ), microalbuminuria (UACR = 30-300 mg/g, eGFR=47.13±23 ml/min/1.73 m 2 ), and macroalbuminuria (UACR >300 mg/g, eGFR=39.68±20 ml/min/1.73 m 2 ). Using fluorogenic and mass spectrometry-based enzyme assays, we measured urinary and plasma ACE2 activity in patients. Urinary ACE2 activity was significantly increased in diabetic patients with normoalbuminuria (0.58±0.2 nmol/hr/mg creatinine), microalbuminuria (1.19 ±0.5 nmol/hr/mg creatinine), and macroalbuminuria (2.265±0.4 nmol/hr/mg creatinine) compared with non-diabetic controls (0.06 ± 0.02 nmols/hr/mg creatinine) (p<0.0001). These results were confirmed by detecting the ACE2 product Ang-(1-7) ( m/z 899) in incubations of urine samples with the natural substrate Ang II ( m/z 1046) using mass spectrometry-based enzyme assays. In addition, urinary ACE2 expression was significantly increased in diabetic patients as determined by western blot analysis (p<0.05). Plasma ACE2 activity was not detectable in control and diabetic patients. In conclusion, urinary ACE2 is increased in diabetic patients with CKD which suggests that urinary ACE2 could be used as an early, noninvasive biomarker for diabetic nephropathy before the onset of microalbuminuria.

scholarly journals Comparison between Pseudomonas aeruginosa siderophores and desferrioxamine for iron acquisition from ferritin

2010 ◽  
Vol 4 (4) ◽  
pp. 631-635 ◽  
Author(s):  
Somporn Srifuengfung ◽  
Susan Assanasen ◽  
Malulee Tuntawiroon ◽  
Sumonrat Meejanpetch
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Iron Acquisition ◽  
Iron Chelator ◽  
Dialysis Membrane ◽  
In Vitro Experiment ◽  
Iron Mobilization ◽  
Ph Values ◽  
Minimum Medium ◽  
Stimulation Of

Abstract Background: Siderophore is an iron chelator produced by microorganism. Pseudomonas aeruginosa produces two siderophores (pyoverdin and pyochelin). Desferrioxamine is a siderophore used in thalassemia patients to treat an iron overload of vital organs. Objective: Compare the ability of pyoverdin, pyochelin, and desferrioxamine for iron mobilization from ferritin. Materials and Methods: In vitro experiment, the ability of P. aeruginosa siderophores and desferrioxamine for iron mobilization from ferritin was compared by using a dialysis membrane assay at pH values of 7.4 and 6.0. Stimulation of P. aeruginosa PAO1 growth by all siderophores was studied in glucose minimum medium. Results: All three compounds were capable of iron mobilization at both pHs. At pH 6.0, the most effectiveness compound was desferrioxamine (31.6%), followed by pyoverdin (21.5%) and pyochelin (13.7%) compared on weight basis, each at 10 μg/mL. At equimolar concentration, their activities were desferrioxamine (38.5±1.2%), followed by pyoverdin (32.0±4.8%) and pyochelin (26.7±1.9%), respectively. Conclusion: The most effective compound in iron mobilization from ferritin was desferrioxamine, followed by pyoverdin and pyochelin respectively.

scholarly journals Predictors of Cardiovascular Autonomic Neuropathy Onset and Progression in a Cohort of Type 1 Diabetic Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
M. Matta ◽  
A. Pavy-Le Traon ◽  
S. Perez-Lloret ◽  
C. Laporte ◽  
I. Berdugo ◽  
...  
Keyword(s):  
Autonomic Neuropathy ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Valsalva Maneuver ◽  
Cardiovascular Autonomic Neuropathy ◽  
Bivariate Analysis ◽  
Diabetic Patients ◽  
Laboratory Assessment ◽  
Low Bmi ◽  
Type 1 Diabetic Patients

Aim. The prevalence of cardiovascular autonomic neuropathy (CAN) in diabetes mellitus is well documented. However, the rate and predictors of both the development and progression of CAN have been less studied. Hereby, we assessed the rate and the major risk factors for CAN initiation and progression in a cohort of type 1 diabetic patients followed over a three-year period. Methods. 175 type 1 diabetic patients (mean age: 50 ± 11 years; female/male: 76/99) with positive bedside screening for CAN were included and underwent 2 standardized autonomic testings using 4 standardized tests (deep breathing, Valsalva maneuver, 30/15 ratio, and changes in blood pressure during standing), separated by 3 ± 1 years. CAN staging was achieved according to the Toronto Consensus Panel on Diabetic Autonomic Neuropathy into 4 categories: absent, possible, confirmed, or severe CAN. Results. Out of the 175 patients included, 31.4% were free of CAN, 34.2% had possible CAN, 24.6% had confirmed CAN, and 9.7% exhibited severe CAN at the first assessment. Among the 103 patients with nonsevere CAN at inclusion, forty-one (39.8%) had an increase of at least one category when reassessed and 62 (60.2%) remained stable. A bivariate analysis indicated that only BMI and exposure to selective serotonin reuptake inhibitors (SSRIs) were significantly different in both groups. A multivariate analysis indicated that lower BMI (OR: 0.15, CI 95%: 0.05–0.48, p=0.003) and SSRI exposure (OR: 4.18, CI 95%: 1.03–16.97, p=0.04) were the sole predictors of CAN deterioration. In the 55 patients negative for CAN at the first laboratory assessment, 12 became positive at the second assessment. Conclusion. No clear predictive factor for CAN onset was identified. However, once present, CAN progression was related to low BMI and SSRI exposure.

scholarly journals Subclinical onychomycosis in patients with type II diabetes

2015 ◽  
Vol 7 (3) ◽  
Author(s):  
Amira Elbendary ◽  
Amira El Tawdy ◽  
Naglaa Zaki ◽  
Mostafa Alfishawy ◽  
Amr Rateb
Keyword(s):  
Early Detection ◽  
Type Ii Diabetes ◽  
Periodic Acid ◽  
Clinical Manifestations ◽  
Diabetic Patients ◽  
Type Ii ◽  
Periodic Acid Schiff ◽  
Cross Sectional ◽  
Uncontrolled Diabetes ◽  
Fungal Organisms

Fungal organisms could be present in the nail without any clinical manifestations. As onychomycosis in diabetics has more serious complications, early detection of such infection could be helpful to prevent them. We aim in this study to assess the possibility of detecting subclinical onychomycosis in type II diabetic patients and addressing possible associated neuropathy. A cross sectional, observational study included patients with type II diabetes with normal big toe nail. All were subjected to nail clipping of the big toe nail, followed by staining with Hematoxylin and Eosin and Periodic-Acid-Schiff (PAS) stains and examined microscopically. A total of 106 patients were included, fungal infection was identified in eight specimens, all were uncontrolled diabetes, and six had neuropathy. Using the nail clipping and microscopic examination with PAS stain to detect such subclinical infection could be an applicable screening test for diabetic patients, for early detection and management of onychomycosis.

scholarly journals Nitric oxide–mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection

2013 ◽  
Vol 210 (5) ◽  
pp. 855-873 ◽  
Author(s):  
Manfred Nairz ◽  
Ulrike Schleicher ◽  
Andrea Schroll ◽  
Thomas Sonnweber ◽  
Igor Theurl ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Iron Acquisition ◽  
Iron Chelator ◽  
Related Factor ◽  
Cellular Iron ◽  
Splenic Macrophages ◽  
Ferroportin 1 ◽  
Pathogen Control

Nitric oxide (NO) generated by inducible NO synthase 2 (NOS2) affects cellular iron homeostasis, but the underlying molecular mechanisms and implications for NOS2-dependent pathogen control are incompletely understood. In this study, we found that NO up-regulated the expression of ferroportin-1 (Fpn1), the major cellular iron exporter, in mouse and human cells. Nos2−/− macrophages displayed increased iron content due to reduced Fpn1 expression and allowed for an enhanced iron acquisition by the intracellular bacterium Salmonella typhimurium. Nos2 gene disruption or inhibition of NOS2 activity led to an accumulation of iron in the spleen and splenic macrophages. Lack of NO formation resulted in impaired nuclear factor erythroid 2-related factor-2 (Nrf2) expression, resulting in reduced Fpn1 transcription and diminished cellular iron egress. After infection of Nos2−/− macrophages or mice with S. typhimurium, the increased iron accumulation was paralleled by a reduced cytokine (TNF, IL-12, and IFN-γ) expression and impaired pathogen control, all of which were restored upon administration of the iron chelator deferasirox or hyperexpression of Fpn1 or Nrf2. Thus, the accumulation of iron in Nos2−/− macrophages counteracts a proinflammatory host immune response, and the protective effect of NO appears to partially result from its ability to prevent iron overload in macrophages

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