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1.
BMJ Case Rep ; 16(5)2023 May 02.
Article in English | MEDLINE | ID: covidwho-2317040

ABSTRACT

A man in his 50s was referred with profound, symptomatic hypercalcaemia. He was diagnosed with primary hyperparathyroidism, confirmed on 99mTc-sestamibi scan. He was treated for the hypercalcaemia and referred to ear, nose and throat (ENT) surgeons for parathyroidectomy, which was delayed due to the COVID-19 pandemic. In the ensuing 18 months, he had five hospital admissions with severe hypercalcaemia requiring intravenous fluids and bisphosphonate infusions. During the last admission, hypercalcaemia was resistant to maximal medical management. Emergency parathyroidectomy was planned, but delayed due to intervening COVID-19 infection. Due to persistent severe hypercalcaemia (serum calcium: 4.23 mmol/L), he was commenced on intravenous steroids, following which serum calcium normalised. Subsequently, he underwent emergency parathyroidectomy, which normalised his serum parathyroid and calcium levels. On histopathological examination, a diagnosis of parathyroid carcinoma was made. On follow-up, patient remained well and normocalcaemic. In patients with primary hyperparathyroidism unresponsive to standard therapy, but responsive to steroids, underlying parathyroid malignancy should be considered.


Subject(s)
COVID-19 , Hypercalcemia , Hyperparathyroidism, Primary , Parathyroid Neoplasms , Male , Humans , Parathyroid Neoplasms/complications , Parathyroid Neoplasms/diagnosis , Parathyroid Neoplasms/surgery , Hypercalcemia/drug therapy , Hypercalcemia/etiology , Calcium , Hyperparathyroidism, Primary/complications , Hyperparathyroidism, Primary/diagnosis , Hyperparathyroidism, Primary/surgery , Pandemics , COVID-19/complications , Parathyroidectomy , Steroids , Parathyroid Hormone
2.
Chembiochem ; 24(10): e202300034, 2023 05 16.
Article in English | MEDLINE | ID: covidwho-2308421

ABSTRACT

CRISPR-LbuCas13a has emerged as a revolutionary tool for in vitro diagnosis. Similar to other Cas effectors, LbuCas13a requires Mg2+ to maintain its nuclease activity. However, the effect of other divalent metal ions on its trans-cleavage activity remains less explored. Herein, we addressed this issue by combining experimental and molecular dynamics simulation analysis. In vitro studies showed that both Mn2+ and Ca2+ could replace Mg2+ as cofactors of LbuCas13a. In contrast, Ni2+ , Zn2+ , Cu2+ , or Fe2+ inhibits the cis- and trans-cleavage activity, while Pb2+ does not affect it. Importantly, molecular dynamics simulations confirmed that calcium, magnesium, and manganese hydrated ions have a strong affinity to nucleotide bases, thus stabilizing the conformation of crRNA repeat region and enhancing the trans-cleavage activity. Finally, we showed that combination of Mg2+ and Mn2+ can further enhance the trans-cleavage activity to allow amplified RNA detection, revealing its potential advantage for in vitro diagnosis.


Subject(s)
Manganese , RNA , Calcium/metabolism , Molecular Conformation , Magnesium , CRISPR-Cas Systems
3.
Front Immunol ; 14: 1143350, 2023.
Article in English | MEDLINE | ID: covidwho-2293386

ABSTRACT

Introduction: Severe COVID-19 is characterized by cytokine storm, an excessive production of proinflammatory cytokines that contributes to acute lung damage and death. Dexamethasone is routinely used to treat severe COVID-19 and has been shown to reduce patient mortality. However, the mechanisms underlying the beneficial effects of dexamethasone are poorly understood. Methods: We conducted transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients with mild disease, and patients with severe COVID-19 with and without dexamethasone treatment. We then treated healthy donor PBMCs in vitro with dexamethasone and investigated the effects of dexamethasone treatment ion channel abundance (by RT-qPCR and flow cytometry) and function (by electrophysiology, Ca2+ influx measurements and cytokine release) in T cells. Results: We observed that dexamethasone treatment in severe COVID-19 inhibited pro-inflammatory and immune exhaustion pathways, circulating cytotoxic and Th1 cells, interferon (IFN) signaling, genes involved in cytokine storm, and Ca2+ signaling. Ca2+ influx is regulated by Kv1.3 potassium channels, but their role in COVID-19 pathogenesis remains elusive. Kv1.3 mRNA was increased in PBMCs of severe COVID-19 patients, and was significantly reduced in the dexamethasone-treated group. In agreement with these findings, in vitro treatment of healthy donor PBMCs with dexamethasone reduced Kv1.3 abundance in T cells and CD56dimNK cells. Furthermore, functional studies showed that dexamethasone treatment significantly reduced Kv1.3 activity, Ca2+ influx and IFN-g production in T cells. Conclusion: Our findings suggest that dexamethasone attenuates inflammatory cytokine release via Kv1.3 suppression, and this mechanism contributes to dexamethasone-mediated immunosuppression in severe COVID-19.


Subject(s)
COVID-19 , Humans , Leukocytes, Mononuclear/metabolism , Calcium/metabolism , Cytokine Release Syndrome/drug therapy , COVID-19 Drug Treatment , Cytokines/metabolism , Dexamethasone/pharmacology , Dexamethasone/therapeutic use
4.
Adv Sci (Weinh) ; 10(10): e2205781, 2023 04.
Article in English | MEDLINE | ID: covidwho-2279755

ABSTRACT

Invasive fungal infections are a growing public health threat. As fungi become increasingly resistant to existing drugs, new antifungals are urgently needed. Here, it is reported that 405-nm-visible-light-activated synthetic molecular machines (MMs) eliminate planktonic and biofilm fungal populations more effectively than conventional antifungals without resistance development. Mechanism-of-action studies show that MMs bind to fungal mitochondrial phospholipids. Upon visible light activation, rapid unidirectional drilling of MMs at ≈3 million cycles per second (MHz) results in mitochondrial dysfunction, calcium overload, and ultimately necrosis. Besides their direct antifungal effect, MMs synergize with conventional antifungals by impairing the activity of energy-dependent efflux pumps. Finally, MMs potentiate standard antifungals both in vivo and in an ex vivo porcine model of onychomycosis, reducing the fungal burden associated with infection.


Subject(s)
Antifungal Agents , Calcium , Animals , Swine , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Antifungal Agents/metabolism , Calcium/metabolism , Fungi/metabolism
5.
PLoS One ; 18(3): e0282873, 2023.
Article in English | MEDLINE | ID: covidwho-2286870

ABSTRACT

The low dietary intake of iodine (I) and selenium (Se) by humans leads to serious health and socioeconomic problems. Therefore, enrichment of plants with I and Se using fertilisers containing these micronutrients is commonly recommended. In this study, we examined the impacts of combined spraying of I as iodide or iodate, Se as selenite or selenate, and calcium (Ca) as Ca-chloride on the enrichment of 'Red Jonaprince' (Malus domestica Borth.) apples, as well as fruit quality and their storability. Sprays were applied 2 weeks before harvest at rates of 0.5 kg I, 0.25 kg Se and 7 kg Ca per ha. Trees not sprayed with these nutrients served as controls. The tested sprays caused leaf burn, but they did not affect the cold injury of buds and shoots. Those sprays had no effect on yield, fruit size and russeting or skin colouring. At harvest, sprayed apples contained about 50 times more I and Se and 30% more Ca than the control fruit. After storage, compared to the control fruit, sprayed apples were firmer, had more organic acids and were less susceptible to disorders, such as bitter pit, internal breakdown and decay caused by Neofabraea spp. The results indicate that preharvest spraying with I, Se and Ca at high rates can be recommended to effectively enrich apples with I and Se and to simultaneously improve their storability.


Subject(s)
Iodine , Malus , Selenium , Humans , Malus/metabolism , Selenium/metabolism , Calcium/metabolism , Biofortification , Calcium, Dietary/metabolism
6.
BMC Endocr Disord ; 22(1): 324, 2022 Dec 19.
Article in English | MEDLINE | ID: covidwho-2255727

ABSTRACT

BACKGROUND: Familial hypocalciuric hypercalcaemia (FHH) is a rare, inherited disorder of extracellular calcium sensing. It is clinically characterised by mild to moderate parathyroid hormone dependent hypercalcaemia, an autosomal dominant pattern of inheritance, and a normal to reduced urinary calcium excretion in spite of high serum calcium. CASE PRESENTATION: We report two cases of FHH in a family caused by a novel pathogenic missense variant in the CaSR gene, p. His41Arg. Case 1, describes a 17 year old female with no significant past medical history, admitted with acute appendicitis requiring laparoscopic appendectomy and reporting a six month history of polydipsia. Routine investigations were significant for hypercalcaemia, corrected calcium 3.19 mmol/L (2.21-2.52mmol/L), elevated parathyroid hormone of 84pg/ml (15-65pg/ml) and a low 24-hour urine calcium of 0.75mmol/24 (2.50-7.50mmol/24). She was initially managed with intravenous fluids and Zolendronic acid with temporary normalisation of calcium though ultimately required commencement of Cinacalcet 30 mg daily for persistent symptomatic hypercalcaemia. Genetic analysis was subsequently positive for the above variant. Case 2, a 50-year-old female, was referred to the endocrine outpatient clinic for the management of type 2 diabetes and reported a longstanding history of asymptomatic hypercalcaemia which had not been investigated previously. Investigation revealed hypercalcaemia; corrected calcium of 2.6 mmol/L (reference range: 2.21-2.52 mmol/L); PTH of 53.7ng/L (reference range: 15-65 ng/L) and an elevated 24-hour urine calcium of 10 mmol/24 (2.50-7.50 mmol/24hr) with positive genetic analysis and is managed conservatively. Despite sharing this novel mutation, these cases have different phenotypes and their natural history is yet to be determined. Two further relatives are currently undergoing investigation for hypercalcaemia and the family have been referred for genetic counselling. CONCLUSION: Accurate diagnosis of FHH and differentiation from classic primary hyperparathyroidism can be challenging, however it is essential to avoid unnecessary investigations and parathyroid surgery. Genetic analysis may be helpful in establishing a diagnosis of FHH in light of the biochemical heterogeneity in this population and overlap with other causes of hypercalcaemia.


Subject(s)
Diabetes Mellitus, Type 2 , Hypercalcemia , Hyperparathyroidism , Kidney Diseases , Female , Humans , Hypercalcemia/diagnosis , Calcium , Hypercalciuria , Parathyroid Hormone , Receptors, Calcium-Sensing/genetics
7.
PLoS One ; 18(3): e0282151, 2023.
Article in English | MEDLINE | ID: covidwho-2255319

ABSTRACT

BACKGROUND: SARS-CoV-2-mediated COVID-19 may cause sudden cardiac death (SCD). Factors contributing to this increased risk of potentially fatal arrhythmias include thrombosis, exaggerated immune response, and treatment with QT-prolonging drugs. However, the intrinsic arrhythmic potential of direct SARS-CoV-2 infection of the heart remains unknown. OBJECTIVE: To assess the cellular and electrophysiological effects of direct SARS-CoV-2 infection of the heart using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). METHODS: hiPSC-CMs were transfected with recombinant SARS-CoV-2 spike protein (CoV-2 S) or CoV-2 S fused to a modified Emerald fluorescence protein (CoV-2 S-mEm). Cell morphology was visualized using immunofluorescence microscopy. Action potential duration (APD) and cellular arrhythmias were measured by whole cell patch-clamp. Calcium handling was assessed using the Fluo-4 Ca2+ indicator. RESULTS: Transfection of hiPSC-CMs with CoV-2 S-mEm produced multinucleated giant cells (syncytia) displaying increased cellular capacitance (75±7 pF, n = 10 vs. 26±3 pF, n = 10; P<0.0001) consistent with increased cell size. The APD90 was prolonged significantly from 419±26 ms (n = 10) in untransfected hiPSC-CMs to 590±67 ms (n = 10; P<0.05) in CoV-2 S-mEm-transfected hiPSC-CMs. CoV-2 S-induced syncytia displayed delayed afterdepolarizations, erratic beating frequency, and calcium handling abnormalities including calcium sparks, large "tsunami"-like waves, and increased calcium transient amplitude. After furin protease inhibitor treatment or mutating the CoV-2 S furin cleavage site, cell-cell fusion was no longer evident and Ca2+ handling returned to normal. CONCLUSION: The SARS-CoV-2 spike protein can directly perturb both the cardiomyocyte's repolarization reserve and intracellular calcium handling that may confer the intrinsic, mechanistic substrate for the increased risk of SCD observed during this COVID-19 pandemic.


Subject(s)
COVID-19 , Induced Pluripotent Stem Cells , Long QT Syndrome , Humans , Myocytes, Cardiac/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Calcium/metabolism , Furin/metabolism , Long QT Syndrome/metabolism , Pandemics , COVID-19/metabolism , SARS-CoV-2/metabolism , Arrhythmias, Cardiac/metabolism , Action Potentials/physiology
8.
PLoS Comput Biol ; 18(9): e1010517, 2022 09.
Article in English | MEDLINE | ID: covidwho-2267223

ABSTRACT

Proximal genetic variants are frequently correlated, implying that the corresponding effect sizes detected by genome-wide association studies (GWAS) are also not independent. Methods already exist to account for this when aggregating effects from a single GWAS across genes or pathways. Here we present a rigorous yet fast method for detecting genes with coherent association signals for two traits, facilitating cross-GWAS analyses. To this end, we devised a new significance test for the covariance of datapoints not drawn independently but with a known inter-sample covariance structure. We show that the distribution of its test statistic is a linear combination of χ2 distributions with positive and negative coefficients. The corresponding cumulative distribution function can be efficiently calculated with Davies' algorithm at high precision. We apply this general framework to test for dependence between SNP-wise effect sizes of two GWAS at the gene level. We extend this test to detect also gene-wise causal links. We demonstrate the utility of our method by uncovering potential shared genetic links between the severity of COVID-19 and (1) being prescribed class M05B medication (drugs affecting bone structure and mineralization), (2) rheumatoid arthritis, (3) vitamin D (25OHD), and (4) serum calcium concentrations. Our method detects a potential role played by chemokine receptor genes linked to TH1 versus TH2 immune response, a gene related to integrin beta-1 cell surface expression, and other genes potentially impacting the severity of COVID-19. Our approach will be useful for similar analyses involving datapoints with known auto-correlation structures.


Subject(s)
COVID-19 , Genome-Wide Association Study , COVID-19/genetics , Calcium , Humans , Integrins , Polymorphism, Single Nucleotide/genetics , Receptors, Chemokine , Vitamin D
9.
Crit Rev Clin Lab Sci ; 59(8): 517-554, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2264438

ABSTRACT

Vitamin D has a well-known role in the calcium homeostasis associated with the maintenance of healthy bones. It increases the efficiency of the intestinal absorption of dietary calcium, reduces calcium losses in urine, and mobilizes calcium stored in the skeleton. However, vitamin D receptors are present ubiquitously in the human body and indeed, vitamin D has a plethora of non-calcemic functions. In contrast to most vitamins, sufficient vitamin D can be synthesized in human skin. However, its production can be markedly decreased due to factors such as clothing, sunscreens, intentional avoidance of the direct sunlight, or the high latitude of the residence. Indeed, more than one billion people worldwide are vitamin D deficient, and the deficiency is frequently undiagnosed. The chronic deficiency is not only associated with rickets/osteomalacia/osteoporosis but it is also linked to a higher risk of hypertension, type 1 diabetes, multiple sclerosis, or cancer. Supplementation of vitamin D may be hence beneficial, but the intake of vitamin D should be under the supervision of health professionals because overdosing leads to intoxication with severe health consequences. For monitoring vitamin D, several analytical methods are employed, and their advantages and disadvantages are discussed in detail in this review.


Subject(s)
Rickets , Vitamin D Deficiency , Humans , Vitamin D/metabolism , Vitamin D/therapeutic use , Calcium , Vitamin D Deficiency/complications , Vitamin D Deficiency/drug therapy , Vitamins , Rickets/complications , Rickets/drug therapy , Calcium, Dietary
10.
Biocontrol Sci ; 27(1): 53-56, 2022.
Article in English | MEDLINE | ID: covidwho-2241371

ABSTRACT

SARS-CoV-2, an acute respiratory syndrome-causing virus, suddenly emerged at the end of 2019 in China, and rapidly spread all over the world. In this study, we examined whether a calcinated calcium solution (ShellCoat) , which has been approved as a food additive in Japan can inactivate SARS-CoV-2. Furthermore, antiviral activity of ShellCoat against SARS-CoV-2 was also evaluated in the presence of organic matter, namely, fetal bovine serum (FBS) . When concentrated SARS-CoV-2 were treated with ShellCoat for 10 sec in presence or absence of FBS as organic matters, the viral titer was decreased more than 4 logs 50% tissue culture infective dose per mL (TCID50/mL) but use of ShellCoat for 20 sec or more under similar experimental conditions the viral titer was below the detection limit (≦2.1 logs TCID50/mL) . These results clearly indicate that the ShellCoat is a powerful antiviral agent against SARS-CoV-2 even in the presence of organic matters.


Subject(s)
COVID-19 , Calcium , Antiviral Agents/pharmacology , Humans , SARS-CoV-2 , Viral Load
11.
Inflammopharmacology ; 30(5): 1479-1491, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2231556

ABSTRACT

COVID-19 is one of the viral diseases that has caused many deaths and financial losses to humans. Using the available information, this virus appears to activate the host cell-death mechanism through Calpain activation. Calpain inhibition can stop its downstream cascade reactions that cause cell death. Given the main roles of Calpain in the entry and pathogenicity of the SARS-CoV-2, its inhibition can be effective in controlling the COVID-19. This review describes how the virus activates Calpain by altering calcium flow. When Calpain was activated, the virus can enter the target cell. Subsequently, many complications of the disease, such as inflammation, cytokine storm and pulmonary fibrosis, are caused by virus-activated Calpain function. Calpain inhibitors appear to be a potential drug to control the disease and prevent death from COVID-19.


Subject(s)
COVID-19 Drug Treatment , Calcium , Calpain/metabolism , Cytokine Release Syndrome , Humans , SARS-CoV-2
12.
Curr Opin Pharmacol ; 68: 102347, 2023 02.
Article in English | MEDLINE | ID: covidwho-2234566

ABSTRACT

Store-Operated Ca2+ entry (SOCE) is recognized as a key mechanism in muscle physiology necessary to refill intracellular Ca2+ stores during sustained muscle activity. For many years the cell structures expected to mediate SOCE in skeletal muscle fibres remained unknown. Recently, the identification of Ca2+ Entry Units (CEUs) in exercised muscle fibres opened new insights into the role of extracellular Ca2+ in muscle contraction and, more generally, in intracellular Ca2+ homeostasis. Accordingly, intracellular Ca2+ unbalance due to alterations in SOCE strictly correlates with muscle disfunction and disease. Mutations in proteins involved in SOCE (STIM1, ORAI1, and CASQ1) have been linked to tubular aggregate myopathy (TAM), a disease that causes muscle weakness and myalgia and is characterized by a typical accumulation of highly ordered and packed membrane tubules originated from the sarcoplasmic reticulum (SR). Achieving a full understanding of the molecular pathways activated by alterations in Ca2+ entry mechanisms is a necessary step to design effective therapies for human SOCE-related disorders.


Subject(s)
Calcium , Myopathies, Structural, Congenital , Humans , Calcium/metabolism , Ion Transport , Mutation , Homeostasis , Myopathies, Structural, Congenital/genetics , Myopathies, Structural, Congenital/metabolism
13.
Front Immunol ; 13: 1022401, 2022.
Article in English | MEDLINE | ID: covidwho-2215267

ABSTRACT

Roles of platelets during infections surpass the classical thrombus function and are now known to modulate innate immune cells. Leukocyte-platelet aggregations and activation-induced secretome are among factors recently gaining interest but little is known about their interplay with severity and mortality during the course of SARS-Cov-2 infection. The aim of the present work is to follow platelets' bioenergetics, redox balance, and calcium homeostasis as regulators of leukocyte-platelet interactions in a cohort of COVID-19 patients with variable clinical severity and mortality outcomes. We investigated COVID-19 infection-related changes in platelet counts, activation, morphology (by flow cytometry and electron microscopy), bioenergetics (by Seahorse analyzer), mitochondria function (by high resolution respirometry), intracellular calcium (by flow cytometry), reactive oxygen species (ROS, by flow cytometry), and leukocyte-platelet aggregates (by flow cytometry) in non-intensive care unit (ICU) hospitalized COVID-19 patients (Non-ICU, n=15), ICU-survivors of severe COVID-19 (ICU-S, n=35), non-survivors of severe COVID-19 (ICU-NS, n=60) relative to control subjects (n=31). Additionally, molecular studies were carried out to follow gene and protein expressions of mitochondrial electron transport chain complexes (ETC) in representative samples of isolated platelets from the studied groups. Our results revealed that COVID-19 infection leads to global metabolic depression especially in severe patients despite the lack of significant impacts on levels of mitochondrial ETC genes and proteins. We also report that severe patients' platelets exhibit hyperpolarized mitochondria and significantly lowered intracellular calcium, concomitantly with increased aggregations with neutrophil. These changes were associated with increased populations of giant platelets and morphological transformations usually correlated with platelets activation and inflammatory signatures, but with impaired exocytosis. Our data suggest that hyperactive platelets with impaired exocytosis may be integral parts in the pathophysiology dictating severity and mortality in COVID-19 patients.


Subject(s)
COVID-19 , Calcium , Humans , SARS-CoV-2 , Leukocytes , Metabolome
14.
J Phys Chem Lett ; 14(1): 88-94, 2023 Jan 12.
Article in English | MEDLINE | ID: covidwho-2185481

ABSTRACT

The receptor-binding domain of the SARS-CoV-2 spike mediates the key to binding the virus to the host receptor, but capturing the molecular signal of this spike RBD remains a formidable challenge. Here, we report a new surface-enhanced Raman spectroscopy (SERS) approach, which used gold nanoparticles prepared by low-speed constant-temperature centrifugation by bromine and calcium ions in two cleaning steps as the enhanced substrate to rapidly and accurately detect spike RBD large protein molecules in body fluids. The detection signal was extremely stable, and the orientation of the spike RBD on the enhanced substrate surface was also determined. This approach was specific in distinguishing different SARS-CoV-2 variants of spike RBD, including Delta, Beta, Gamma, and Omicron. Additionally, the enhanced substrate can identify biologically active or inactive spike RBD. This two-step cleaning enhanced substrate opens up opportunities not only for early diagnostics of SARS-CoV-2 virus but also for developing targeted drugs against viruses.


Subject(s)
Body Fluids , COVID-19 , Metal Nanoparticles , Humans , Bromides , COVID-19/diagnosis , Calcium , Gold , SARS-CoV-2 , Ions
15.
Maturitas ; 169: 2-9, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2165686

ABSTRACT

INTRODUCTION: There is increasing evidence that vitamin D has widespread tissue effects. In addition to osteoporosis, vitamin D deficiency has been associated with cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However, the effect of vitamin D supplementation on non-skeletal outcomes requires clarification, especially in postmenopausal women. AIM: This position statement provides an evidence-based overview of the role of vitamin D in the health of postmenopausal women based on observational and interventional studies. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Vitamin D status is determined by measuring serum 25-hydroxyvitamin D levels. Concentrations <20 ng/ml (<50 nmol/l) and <10 ng/ml (<25 nmol/l) are considered to constitute vitamin D deficiency and severe deficiency, respectively. Observational data suggest an association between vitamin D deficiency and adverse health outcomes in postmenopausal women, although they cannot establish causality. The evidence from randomized controlled trials concerning vitamin D supplementation is not robust, since many studies did not consider whether people were deficient at baseline. Moreover, high heterogeneity exists in terms of the population studied, vitamin D dosage, calcium co-administration and duration of intervention. Concerning skeletal health, vitamin D deficiency is associated with low bone mass and an increased risk of fractures. Vitamin D supplementation at maintenance doses of 800-2000 IU/day (20-50 µg/day), after repletion of vitamin D status with higher weekly or daily doses, may be of benefit only when co-administered with calcium (1000-1200 mg/day), especially in the elderly populations and those with severe vitamin D deficiency. Concerning cardiovascular disease, vitamin D deficiency is associated with an increased prevalence of cardiovascular risk factors, mainly metabolic syndrome, type 2 diabetes mellitus and dyslipidemia. Vitamin D deficiency, especially its severe form, is associated with an increased risk of cardiovascular events (coronary heart disease, stroke, mortality), independently of traditional risk factors. Vitamin D supplementation may have a modestly beneficial effect on lipid profile and glucose homeostasis, especially in obese individuals or those ≥60 years old and at doses of ≥2000 IU/day (≥50 µg/day). However, it has no effect on the incidence of cardiovascular events. Concerning cancer, vitamin D deficiency is associated with increased incidence of and mortality from several types of cancer, such as colorectal, lung and breast cancer. However, the data on other types of gynecological cancer are inconsistent. Vitamin D supplementation has no effect on cancer incidence, although a modest reduction in cancer-related mortality has been observed. Concerning infections, vitamin D deficiency has been associated with acute respiratory tract infections, including coronavirus disease 2019 (COVID-19). Vitamin D supplementation may decrease the risk of acute respiratory tract infections and the severity of COVID-19 (not the risk of infection). Concerning menopausal symptomatology, vitamin D deficiency may have a negative impact on some aspects, such as sleep disturbances, depression, sexual function and joint pains. However, vitamin D supplementation has no effect on these, except for vulvovaginal atrophy, at relatively high doses, i.e., 40,000-60,000 IU/week (1000-1500 IU/week) orally or 1000 IU/day (25 µg/day) as a vaginal suppository.


Subject(s)
Dietary Supplements , Menopause , Vitamin D , Aged , Female , Humans , Calcium , Calcium, Dietary , Cardiovascular Diseases/complications , COVID-19 , Diabetes Mellitus, Type 2/complications , Neoplasms/complications , Neurodegenerative Diseases , Vitamin D Deficiency/complications , Vitamin D Deficiency/drug therapy , Vitamin D Deficiency/epidemiology
16.
Life Sci ; 313: 121271, 2023 Jan 15.
Article in English | MEDLINE | ID: covidwho-2159516

ABSTRACT

Mitochondria are dynamic cellular organelles with diverse functions including energy production, calcium homeostasis, apoptosis, host innate immune signaling, and disease progression. Several viral proteins specifically target mitochondria to subvert host defense as mitochondria stand out as the most suitable target for the invading viruses. They have acquired the capability to control apoptosis, metabolic state, and evade immune responses in host cells, by targeting mitochondria. In this way, the viruses successfully allow the spread of viral progeny and thus the infection. Viruses employ their proteins to alter mitochondrial dynamics and their specific functions by a modulation of membrane potential, reactive oxygen species, calcium homeostasis, and mitochondrial bioenergetics to help them achieve a state of persistent infection. A better understanding of such viral proteins and their impact on mitochondrial forms and functions is the main focus of this review. We also attempt to emphasize the importance of exploring the role of mitochondria in the context of SARS-CoV2 pathogenesis and identify host-virus protein interactions.


Subject(s)
Mitochondria , Viral Proteins , Humans , Calcium/metabolism , Mitochondria/metabolism , Mitochondria/virology , RNA, Viral/metabolism , Viral Proteins/metabolism , Viruses/pathogenicity
17.
Curr Hypertens Rev ; 19(1): 4-6, 2023.
Article in English | MEDLINE | ID: covidwho-2154507
18.
BMJ Case Rep ; 15(11)2022 Nov 14.
Article in English | MEDLINE | ID: covidwho-2119108

ABSTRACT

Acute hypocalcaemia can be life-threatening and must be diagnosed promptly. The gold-standard investigation is ionised calcium, which is measured on most blood gas analysers. Total calcium measurements are inaccurate in severe depletion even if 'corrected' or 'adjusted' for albumin. We present an illustrative case of a woman in her 30s with symptomatic hypocalcaemia and a very low ionised calcium on VBG analysis. Emergency calcium replacement was delayed due to a falsely reassuring corrected calcium result. Our discussion includes a systematic literature review on the use of ionised calcium in emergency and acute medical settings. We suggest cognitive biases that may explain clinical over-reliance on corrected calcium, and call for the inclusion of ionised calcium values in major treatment guidelines for acute hypocalcaemia.


Subject(s)
Hypocalcemia , Female , Humans , Hypocalcemia/diagnosis , Hypocalcemia/drug therapy , Calcium/therapeutic use
19.
Int J Mol Sci ; 23(19)2022 Oct 09.
Article in English | MEDLINE | ID: covidwho-2066143

ABSTRACT

Vitamin D deficiency has increased in the general population and is a public health issue. Vitamin D plays an important role in regulating the immune system, e.g., by modulating the production of inflammatory cytokines. In most countries, the recommended maximal daily dose of vitamin D3 is 4000 IU (100 µg) per day. In this study, we investigated whether a single vitamin D3 bolus can reduce the levels of the inflammatory markers interleukin (IL) 6, IL8 and tumor necrosis factor (TNF) within one month. Fifty healthy Saudi males were recruited from the local community in Jeddah city and were orally supplemented with a single dose of 80,000 IU vitamin D3. Serum samples were collected at time points 0, 1 and 30 days, and serum levels of IL6, IL8 and TNF, parathyroid hormone (PTH), 25-hydroxyvitamin D3 (25(OH)D3), triglycerides, cholesterol, calcium (Ca2+) and phosphate (PO4-) were determined. On average, the vitamin D3 bolus resulted in a significant increase in vitamin D status as well as in a significant decrease in the levels of inflammatory cytokines even one month after supplementation without changing serum Ca2+, PO4- or lipid levels. In conclusion, single high-dose vitamin D3 supplementation is safe for reducing inflammation markers and may lead to an update of current recommendations for vitamin D intake, in order to prevent critical health problems.


Subject(s)
Cholecalciferol , Vitamin D Deficiency , Biomarkers , Calcium , Dietary Supplements , Humans , Interleukin-6 , Interleukin-8 , Male , Parathyroid Hormone , Phosphates , Saudi Arabia , Triglycerides , Tumor Necrosis Factors , Vitamin D , Vitamin D Deficiency/drug therapy , Vitamins
20.
Sci Rep ; 12(1): 16878, 2022 10 07.
Article in English | MEDLINE | ID: covidwho-2062259

ABSTRACT

Recent reports demonstrate that SARS-CoV-2 utilizes cell surface heparan sulfate as an attachment factor to facilitate the initial interaction with host cells. Heparan sulfate interacts with the receptor binding domain of SARS-CoV-2 spike glycoprotein, and blocking this interaction can decrease cell infection. We and others reported recently that the family of compounds of 2,5-dihydroxyphenylic acid interferes with the binding of the positively charged groove in growth factor molecules to negatively charged cell surface heparan sulfate. We hypothesized that Calcium Dobesilate (CaD)-calcium salt of 2,5-dihydroxyphenylic acid-may also interfere with the binding of SARS-CoV-2 spike protein to heparan sulfate. Using lentiviral SARS-CoV-2 spike protein pseudotyped particles we show that CaD could significantly reduce pseudovirus uptake into endothelial cells. On the contrary, CaD did not affect cell infection with VSVG-expressing lentivirus. CaD could also prevent retention of SARS-CoV-2 spike protein in ex vivo perfused mouse kidney. Using microfluidic culture of endothelial cells under flow, we show that CaD prevents spike protein interaction with heparan sulfate glycocalyx. Since CaD has no adverse side effects and is approved in humans for other medical indications, our findings can rapidly translate into clinical studies.


Subject(s)
COVID-19 Drug Treatment , Calcium Dobesilate , Animals , Calcium/metabolism , Endothelial Cells/metabolism , Heparitin Sulfate/metabolism , Heparitin Sulfate/pharmacology , Humans , Mice , Protein Binding , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Virus Attachment
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