Modern views on the metabolism and biological effects of vitamin D

Vitamin D is a steroid hormone that plays a crucial role in maintaining normal bone condition and calcium homeostasis. In recent years, vitamin D has become a hot topic of endocrino-logical research, largely Due to the COVID-19 pandemic and the likely correlation between hypovitaminosis D and a high risk of chronic lung disease and associated mortality. Recent studies have shown that vitamin D exhibits a complex multistage metabolism and acts as a hormone on many extracellular targets. This review examines some new intriguing and as yet unclear aspects of vitamin D metabolism, such as new concepts of enzyme regulation, new pleiotropic effects of vitamin D receptor activation (VDR), and epigenetic effects. The mechanisms of vitamin D synthesis in the skin, its metabolism in the hepatic cytochrome P450 system, catabolism, metabolites and transport, gene control and epigenetic modulation are considered in Detail. In addition to the well-known role of vitamin D in calcium and bone metabolism, it has many pleiotropic extraskeletal effects, including potent effects on the immune system, cardiovascular system, adipose tissue and glucose/ lipid metabolism, muscle and more. Experimental studies have shown that VDRs are expressed by cancer cell lines. Recent studies have shown a link between low levels of vitamin D and almost all aspects of the metabolic syndrome, such as type 2 diabetes, fasting blood glucose, hypertension, dyslipidemia, obesity and insulin re-sistance. Several studies have focused on the role of vitamin D in adipose tissue biology. In particular, a negative correlation between vitamin D and leptin or resistin is shown, as well as an inverse correlation with adiponectin. Recent studies in vitamin D-deficient mice have shown impaired secretion of glucose-stimulated insulin by pancreatic islets. Vitamin D is thought to play a role in the pathogenesis and progression of cancer, and vitamin D analogues can slow cancer progression and metastasis. It is concluded that vitamin D is a molecule with several endocrine, paracrine and auto-crine effects on many tissues and organs, in addition to maintaining skeletal homeostasis. Research in this area, which aims to clarify the pleiotropy of many effects of vitamin D and its metabolites, continues. © 2022, Zaslavsky Publishing House. All rights reserved.

Relationship between COVID-19 and liver diseases: The role of hepatologists in clinical practice.

COVID-19 due to severe acute respiratory syndrome coronavirus 2, which has become a global pandemic, produces elevated liver enzymes, especially in severe cases. The mechanism suggests involvement of an administrated drug, cytokine storm, or hypoxia, etc., as opposed to virus-induced direct damage. If liver enzymes are elevated in COVID-19, we should evaluate for the presence of other liver diseases, and strictly follow-up liver enzyme values. In patients with COVID-19 complicated by chronic liver disease, we will use telemedicine/visits by phone, so as not to interrupt the treatment of the underlying disease, avoid unnecessary outpatient visits, and strive to halt the spread of the infection. Metabolism-associated fatty liver disease, which is often related to obesity, diabetes, and hypertension, may be a risk factor for COVID-19 severity. International academic societies have recommended guidance outlining the evidence to date regarding the management of patients with COVID-19 and liver disorders, and chronic liver disease under the COVID-19 pandemic.Copyright 2020 The Japan Society of Hepatology.

Bioactive compounds of Jingfang Granules against SARS-CoV-2 virus proteases 3CLpro and PLpro.

OBJECTIVE: Jingfang Granules have been recommended for the prevention and treatment of corona virus disease 2019 (COVID-19). Through chemical analysis and bioactivity evaluation, this study aims to elucidate the potential effective components of Jingfang Granules. METHOD(S): The inhibitory acti-vities of Jingfang Granules extract against 3-chymotrypsin-like protease (3CLpro), papain like protease (PLpro), spike protein receptor-binding domain (S-RBD) and human cyclooxygenase-2 (COX-2) were evaluated using enzyme assay. The antitussive effects were evaluated using the classical ammonia-induced cough model. The chemical constituents of Jingfang Granules were qualitatively and quantitatively analyzed by liquid chromatography-mass spectrometry (LC/MS). The 3CLpro and PLpro inhibitory activities of the major compounds were determined by enzyme assay, molecular docking, and site-directed mutagenesis. RESULT(S): Jingfang Granules exhibited 3CLpro and PLpro inhibitory activities, as well as COX-2 inhibitory and antitussive activities. By investigating the MS/MS behaviors of reference standards, a total of fifty-six compounds were characterized in Jingfang Granules. Sixteen of them were unambiguously identified by comparing with reference standards. The contents of the 16 major compounds were also determined, and their total contents were 2 498.8 mug/g. Naringin, nodakenin and neohesperidin were three dominating compounds in Jingfang Granules, and their contents were 688.8, 596.4 and 578.7 mug/g, respectively. In addition, neohesperidin and naringin exhibited PLpro inhibitory activities, and the inhibition rates at 8 mumol/L were 53.5% and 46.1%, respectively. Prim-O-glucosylcimifugin showed significant inhibitory activities against 3CLpro and PLpro, and the inhibitory rates at 8 mumol/L were 76.8% and 78.2%, respectively. Molecular docking indicated that hydrogen bonds could be formed between prim-O-glucosylcimifugin and amino acid residues H163, E166, Q192, T190 of 3CLpro (binding energy, -7.7 kcal/mol) and K157, D164, R166, E167, T301 of PLpro(-7.3 kcal/mol), respectively. Site-directed mutagenesis indicated amino acid residue K157 was a key active site for the interaction between prim-O-glucosylcimifugin and PLpro. CONCLUSION(S): Prim-O-glucosylcimifugin, neohesperidin, and naringin as the major compounds from Jingfang Granules could inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus proteases 3CLpro and PLpro. The results are valuable for rational clinical use of Jingfang Granules.

Comparison of Comorbidities between Adults and Children with Glycogen Storage Disease Type Ia (GSDIA)

Objectives: Glycogen Storage Disease Type Ia (GSDIa) is a rare inherited disorder resulting in acute hypoglycemia due to impaired release of glucose from glycogen. Despite dietary management practices to prevent hypoglycemia in patients with GSDIa, complications still occur in children and throughout adulthood. This retrospective cohort study compared the prevalence of complications in adults and children with GSDIa. Method(s): Using ICD-10 diagnosis codes, the IQVIA Pharmetrics Plus database was searched for patients with >=2 GSDI claims (E74.01) from January 2016 through February 2020, with >=12 months continuous enrollment beginning prior to March 2019 (for one year of follow-up before COVID-19), and no inflammatory bowel disease diagnoses (indicative of GSDIb). Complication prevalence in adults and children with GSDIa was summarized descriptively. Result(s): In total, 557 patients with GSDIa were identified (adults, 67%;male, 63%), including 372 adults (median age, 41 years) and 185 children (median age, 7 years). Complications occurring only in adults were atherosclerotic heart disease (8.6%), pulmonary hypertension (3.0%), primary liver cancer (1.9%), dialysis (0.8%), and focal segmental glomerulosclerosis (0.3%). Other complications with the greatest prevalence in adults/children included gout (11.8%/0.5%), insomnia (10.0%/1.1%), osteoarthritis (22.0%/2.7%), severe chronic kidney disease (4.3%/0.5%), malignant neoplasm (10.8%/1.6%), hypertension (49.7%/8.7%), acute kidney failure (15.3%/2.7%), pancreatitis (3.0%/0.5%), gallstones (7.8%/1.6%), benign neoplasm (37.4%/8.1%), hepatocellular adenoma (7.0%/1.6%), neoplasm (41.1%/9.7%), and hyperlipidemia (45.2%/10.8%). Complications with the greatest prevalence in children/adults included poor growth (22.2%/1.9%), gastrostomy (29.7%/3.2%), kidney hypertrophy (2.7%/0.8%), seizure (1.6%/0.5%), hypoglycemia (27.0%/11.3%), hepatomegaly (28.7%/15.9%), kidney transplant (1.6%/1.1%), diarrhea (26.5%/18.6%), nausea and/or vomiting (43.8%/35.8%), acidosis (20.0%/17.2%), and anemia due to enzyme disorders (43.8%/40.6%). Conclusion(s): GSDIa is associated with numerous, potentially serious complications. Compared with children, adults with GSDIa had a greater prevalence of chronic complications, potentially indicating the progressive nature of disease. Children with GSDIa had more acute complications related to suboptimal metabolic control.Copyright © 2023

Ferritin - novel uses of a well-known marker in paediatrics

Serum ferritin is one of the most widely used laboratory tests and is associated with both iron deficiency and iron overload. Currently, more and more attention is paid to the involvement of ferritin in processes other than iron metabolism. Low serum ferritin is unanimously associated with iron deficiency, while elevated serum ferritin may be a consequence of various medical conditions such as iron overload, an inflammatory process, SARS-CoV-2, organ failure, cancer, and endocrine disorders, including metabolic syndrome. We present a review of the literature on the role of ferritin in a variety of less obvious disease states in children.Copyright © 2023 Termedia Publishing House Ltd.. All rights reserved.

Should Young Covid-19 Patients be Suplemented with Vitamin D?

It is well known that vitamin D's general immunomodulatory actions are helpful in viral infections and that a shortage is linked to a more serious prognosis for Covid-19. In this sistematic review, we examined the existing literature on evidence as to whether there is also link between vitamin D range levels in pediatric population and the outcome of the Covid-19 infection. We looked for studies that measured vitamin D blood concentrations and examined the effects of vitamin D supplementation in young infected patients. Vitamin D may decrease the risk of respiratory infections in a number of ways through its interactions with numerous cells, including by decreasing viral survival and replication, reducing the cytokine storm, raising angiotensin-converting enzyme 2 concentrations (ACE2) while not damaging the endothelial integrity. The incidence or severity of Covid-19 is linked with blood 25-hydroxyvitamin D concentrations, according to many observational studies. However experimental verification is still needed. Given their safety and broad therapeutic window, vitamin D supplements seem to be an effective way for individuals and doctors to prevent or treat Covid-19. Nonetheless, the outcomes of significant vitamin D randomized controlled trials are further needed.Copyright © 2022 Maria Nicolae et al., published by Sciendo.

US drug approvals rise in 2020 over previous year

Several medicines were approved as first treatments, including Gilead Sciences' Veklury (remdesivir) for patients with COVID-19 who require hospitalization (4);Amivas' artesunate for injection for severe malaria (5);Horizon Therapeutics Ireland DAC's Tepezza (teprotumumab-trbw), an antibody drug conjugate (ADC) for treating thyroid eye disease (6);and Ultragenyx Pharmaceutical's Dojolvi (triheptanoin) and Alnylam Pharmaceuticals' Oxlumo (lumasiran), both first treatments for metabolic disorders-Dojolvi for treating paediatric and adult patients with molecularly confirmed long-chain fatty acid oxidation disorders (7) and Oxlumo (lumasiran) for treating the rare genetic disorder, primary hyperoxaluria type 1 (8). Blueprint Medicines Corporation) for treating unresectable or metastatic gastrointestinal stromal tumours harboring a platelet-derived growth factor receptor alpha exon 18 mutation (9);Koselugo (selumetinib, AstraZeneca Pharmaceuticals), for neurofibromatosis type 1 (10);Pemazyre (pemigatinib, Incyte Corporation), for certain types of previously treated, advanced bile duct cancer (cholangiocarcinoma) (11);Tabrecta (capmatinib, Novartis) for non-small cell lung cancer that has spread to other parts of the body and whose tumours have mutations that lead to MET exon 14 skipping (12);and Retevmo (selpercatinib, Loxo Oncology, a subsidiary of Eli Lilly and Company) for treating three types of tumours with alterations of the "rearranged during transfection" gene (13). Gilead, "U.S. FDA Approves Kite's Tecartus, the First and Only CAR T Treatment for Relapsed or Refractory Mantle Cell Lymphoma," Press Release, 24 July 2020.

Prevention of vitamin D deficiency in children. The state of the problem in the world and in Ukraine.

The article presents current data on the prevalence of vitamin D deficiency and criteria for its deficiency in children in different countries. Vitamin D is recognized as one of the most important vitamins involved in many biochemical processes in the body. Its active metabolites play a key role in calcium absorption, bone mineralization and promote phosphate and magnesium metabolism. At the same time, in addition to affecting mineral metabolism, there is a wide range of conditions in which vitamin D also plays a preventive role. Vitamin D has been shown to play a vital role in innate immunity maintenance and is important in prevention of several diseases, including infections, autoimmune diseases, certain forms of cancer, type 1 and 2 diabetes, and cardiovascular diseases. Vitamin D is of particular importance for newborns and young children. This vitamin is involved in important physiological regulatory processes such as bone metabolism, lung development, maturation of the immune system and differentiation of the nervous system. Vitamin D deficiency increases risks of neonatal sepsis, necrotizing enterocolitis, respiratory distress syndrome, and bronchopulmonary dysplasia. Adequate intake of vitamin D and calcium during childhood can reduce the risk of osteoporosis and other diseases associated with vitamin D deficiency in adults. Recently, vitamin D deficiency has shown to be a potential risk factor for COVID-19 propensity. It has been established that to date most scientific pediatric societies have recognized the need to prevent vitamin D deficiency in healthy children of all ages, but data on the dosage of vitamin D in its prophylactic use differ. Most scientific societies recommend an average of 400-600 IU per day of vitamin D for prophylactic purposes. The analysis of published data shows the need to follow a strategy based on an individual approach, taking into account physiological characteristics, individual requirements and lifestyle.Copyright © 2021 University of Tartu Press. All rights reserved.

Presence of rare potential pathogenic variants in subjects under 60 years old with very severe or fatal COVID-19

Background/Objectives: Genetic variants affecting host defense against pathogens may help explain COVID-19 fatal outcomes. Our aim was to identify rare genetic variants related to COVID-19 severity in a selected group of patients under 60 years who required intubation or resulting in death. Method(s): Forty-four very severe COVID-19 patients were selected from the Spanish STOP-Coronavirus cohort, which comprises more than 3,500 COVID-19 patients. Genotype was performed by whole exome sequencing and variants were selected by using a gene panel of 867 candidate genes (immune response, primary immunodeficiencies or coagulation, among other). Variants were filtered, priorized and their potential pathogenicity was assessed following ACGM criteria. Result(s): We detected 44 different variants of interest, in 29 different patients (66%). Some of these variants were previously described as pathogenic (26%). Mostly, the candidate variants were located in genes related to immune response (38%), congenital disorders of glycosylation (14%) or damaged DNA binding genes (9%). A network analysis, showed three main components, consisting of 25 highly interconnected genes related to immune response and two additional networks enriched in carbohydrate metabolism and in DNA metabolism and repair processes. Conclusion(s): The variants identified affect different, but interrelated, functional pathways such as immune response and glycosylation. Further studies are needed for confirming the ultimate role of the new candidate genes described in the present study on COVID-19 severity.

RHEUMATOLOGISTS BEWARE OF LOW ALP: A CASE OF HYPOPHOSPHATASIA MISDIAGNOSED AS FIBROMYALGIA, CAUSING LONG DIAGNOSTIC DELAY

BackgroundHypophosphatasia(HPP), a rare, inherited metabolic disease featuring low serum alkaline phosphatase (ALP) activity due to ALPL (encoding tissue non-specific alkaline phosphatase) gene mutation[1,2]. A wide-ranging clinical spectrum is often seen due to defective mineralisation affecting teeth, bones, joints and muscles[1]. This disease has a prevalence of 1/6370 in Europe and is often misdiagnosed and underdiagnosed with a diagnostic delay of more than ten years[1] The treatment is often supportive for milder cases and enzyme replacement therapy in severe cases.ObjectivesTo share this case to raise awareness among Rheumatologists.MethodsThis 58-year-old Caucasian female had her first HPP symptom as early eruption of deciduous teeth, along with recurrent dental infections and gum problems. She was diagnosed with flat feet at age five, had a big toe fracture at sixteen, followed by a metatarsal fracture. She experienced leg muscle cramps and aches, affecting her performance in sport during school life.At the age of thirty she began noticing weakness in arms and legs, which progressed over the years. She faced significant early morning stiffness along with painful ribs, hips, knees, shoulders, and small joints of feet when walking.She was diagnosed with Fibromyalgia at the age of forty-four. The following ten years she met numerous specialists including rheumatologist, pain specialist and physiotherapists. She was also diagnosed with early osteoarthritis, pernicious anaemia, hyperlipidemia, functional neurological syndrome, and central sensitization syndrome. She had multiple trials of steroids and opioids, all of which were stopped either due to side effects or inefficiency.A major flare of symptoms five years ago rendered her bedbound for three months, following which a chemical pathologist noticed a persistent low ALP levels and decided to investigate for HPP. It took another four years to complete these investigations due to the coronavirus pandemic.Currently, she is unable to weight bear or climb stairs and must stay indoors or in bed during flareup. She moved into a ground floor flat at the age of 54 and use a walking stick occasionally. By 58, she is unable to work and had given up her own business due to pain, weakness, and disability.ResultsOn clinical assessment, her height is 160 cm, faced difficulty getting up from chair, has an antalgic waddling gait, with a 6-minute walking distance of 60 metre, stopped after three minutes, and had a Brief Pain Inventory pain severity score of 7/10. Her ALP level is 24 U/L and PLP/PA ratio is 18.8 (ref < 5), and genetic testing showed heterozygous missense variant of ALPL gene mutation.ConclusionIt took more than forty years to reach a conclusive diagnosis of childhood onset HPP. Low ALP level is a signature of HPP and warrants investigations. Diagnosis can be challenging due to the rareness and variable presentation, however recognition of HPP features is crucial for timely referral, optimal disease management and potential improvement in quality of life.References[1]Högler W, Langman C, Gomes da Silva H, Fang S, Linglart A, Ozono K, Petryk A, Rockman-Greenberg C, Seefried L, Kishnani PS. Diagnostic delay is common among patients with hypophosphatasia: initial findings from a longitudinal, prospective, global registry. BMC Musculoskelet Disord. 2019 Feb 14;20(1):80. doi:10.1186/s12891-019- 2420-8. PMID: 30764793;PMCID: PMC6376686.[2]Injean P, Lee S, Downey C. Hypophosphatasia May Be Misdiagnosed as Fibromyalgia: A Single Center Experience []. Arthritis Rheumatol. 2020;72 (suppl 10). https://acrs.org//hypophosphatasia-may-be-misdiagnosed-as- ibromyalgia-a-single-center-experience/. Accessed January 14, 2023.[3]Lefever E, Witters P, Gielen E, Vanclooster A, Meersseman W, Morava E, Cassiman D, Laurent MR. Hypophosphatasia in Adults: Clinical Spectrum and Its Association With Genetics and Metabolic Substrates. J Clin Densitom. 2020 Jul-Sep;23(3):340- 48. doi: 10.1016/j.jocd.2018.12.006. Epub 2018 Dec 21. PMID: 30655187.Acknowledgements:N L.Disclosure of InterestsNone Declared.

Classic endocrine disorders: implications for cardiovascular disease

Chronic underproduction or autonomous oversecretion of hormone by endocrine glands has implications for the development and progression of cardiovascular disease. Hormonal effects on the vasculature may be direct, for example, tachycardia and atrial arrhythmias in hyperthyroidism, or mediated indirectly via adverse profiles of one or more major cardiovascular risk factors, for example, arterial hypertension in Conn's syndrome. The timescale of vascular effects may be relatively rapid, for example, resting tachycardia or atrial fibrillation precipitated by hyperthyroidism, or long-term, for example, atherosclerosis associated with acromegaly or hypopituitarism of long duration. The COVID-19 pandemic has highlighted clinically important interactions between the endocrine, metabolic, and cardiovascular systems. Endocrinologists and cardiologists will often need to collaborate closely in the management of patients with endocrine-associated vascular disease. © 2023 Elsevier Inc. All rights reserved.

Effects of training and protein/carbohydrate supplementation by food on strength, body composition and bone metabolism in postmenopausal women

Background: Menopause is associated with impairments of health, e.g. cardiovascular disease, changes in body composition, decrease in bone density. Physical activity and nutrition strategies have been demonstrated to counteract some of these disabilities. Aim of the present study was to analyze the impact of 3 months of strength and endurance training combined with protein/carbohydrate supplementation on strength, body composition and bone metabolism in postmenopausal women. Method(s): 62 postmenopausal women were recruited. Measurements: Body composition by BIA. Strength of leg, chest and handgrip. delta44Ca/42Ca in blood and urine as proxies for bone metabolism, samples were analyzed by mass spectrometry. Participants completed 2/week endurance training (walking) for 60 minutes (60-75% km/h of 4mmol threshold) and a whole-body strength training 1/week for 60 minutes (online). In addition, the intervention group (IG) received 100g of sour milk cheese and 76g of white bread (35.3 g carbohydrate, 36.1 g protein, 3.5 g fat, 321 kcal) after each training. Result(s): Training results in an anabolic effect on bone metabolism, here protein/carbohydrate supplementation does not show additive effects. Training resulted in an increase of leg and hand grip strength. For hand grip strength an additive effect could be demonstrated after protein/carbohydrate supplementation. Both groups increased muscle mass and reduced fat mass, although the results were not significant. Discussion(s): Training was effective, showing an increase in strength. Additive effects of the nutritional intervention could be only observed for hand grip strength. This may be due to a weak compliance of the protein/carbohydrate supplementation by a meal while corona pandemic. Also, because of the endurance parts, the training was not specifically designed to increase strength. Nevertheless, even this mild training has a remarkably strong impact on bone metabolism. Conclusion(s): Even if the effects are faint, the data of this study provide evidence that protein/carbohydrate supplementation, also by food, supports the events of training on strength. Training has a strong impact on bone metabolism in postmenopausal women. The subjects respond very individually to training and nutrition interventions. Training consequentially is to be personalized.Copyright © 2023

Mucormycosis Metabolic Network Modeling: A Constraint-Based Approach

Mucormycosis is an uncommon illness caused by the fungus Mucorales. India was concerned about mucormycosis and COVID-19 in 2020. To minimize morbidity and occurrence, prevent, and treat mucormycosis, analysis is required. Combining systems biology and bioinformatics-based mucormycosis research, this study simulates the Genome-scale metabolic model (GSSM) of a Rhizopus oryzae strain for the comprehension of the organism's metabolic mechanism. Several key metabolic pathways for a mucormycosis-causing fungus strain were identified in research publications and targeted for inclusion in a model of a metabolic network. Based on the Flux Balance Analysis (FBA) approach, an integrated model of these pathways at the scale of the genome's metabolism was developed and appropriate constraints were applied to the numerous reactions involved in Rhizopus oryzae's metabolism using the COBRA package in MATLAB. Hence, unique evidence of pharmacological targets and biomarkers that may function as diagnostic, early analytic, and therapeutic agents in mucormycosis was discovered. Our study investigates the role of key metabolites in the model by applying constraints and altering fluxes, which provides valuable candidates for drug development. . © 2023 IEEE.

IDDF2023-ABS-0045 Spatiotemporal immune landscape of Mas-driven pro-inflammatory microenvironment with hyperactivated glycolysis in acetaminophen-induced liver injury

IDDF2023-ABS-0045 Figure 1 IDDF2023-ABS-0045 Figure 2 IDDF2023-ABS-0045 Figure 3 IDDF2023-ABS-0045 Figure 4

A prospective study to evaluate the role of cholesterol metabolism related genes expression in predicting clinical outcome of patients with severe COVID-19

Background/Objectives: Latest studies have stressed the relevance of cholesterol metabolism with susceptibility to COVID-19 and its severity. We have previously shown downregulation of low-density lipoprotein particle receptor pathway in severe COVID-19 patient surviving compared to non-surviving(1). We aimed to assess the over-time expression changes of its relevant genes in severe COVID-19 patients with different outcomes (survivors/ non-survivors). Method(s): Blood samples were taken from 39 severe COVID-19 patients without chronic diseases twice: on the day of admission to the intensive care (T1) and in one week (T2). Within 30-day follow-up 18 patients recovered and 21 patients died. 20 individuals never previously infected with COVID-19 were also enrolled. Expression levels of studied genes in peripheral blood lymphocytes were analyzed by real-time PCR with TaqMan assay. Result(s): Increased expression of STAB1 at T2, PPARgamma at T1 and CD36 at T1 and T2 were revealed in COVID-19 patients regardless of the outcome compared to controls (p < 0.05). Interesting, that in respective groups of COVID-19 patients increased STAB1, decreased PPARgamma and in survivors decreased LRP6 expression were revealed at T2 compared to T1 (p < 0.01). Also, STAB1 expression was decreased in survivors compared to non-survivors at T2 (p=0.017). Conclusion(s): Our study revealed, that patients with severe COVID-19 are characterized by increased expression of cholesterol metabolism related genes, withmore pronounced decrease of expression of these genes over time for survivors. Increased STAB1 expression may be considered as a predictor of poor COVID-19 prognosis.

Renal Toxicity Boxed Warnings of Drugs Marketed in the US

Objectives: To assess the characteristics of FDA renal toxicity boxed warnings (formerly called Black Box Warning) included in the labels of drugs approved by the FDA and marked in the US. Method(s): We extracted the labels of human prescription drugs with renal toxicity boxed warnings from the "FDA Label: Full-Text Search of Drug Product Labeling" database, FDA regulatory information from drugs@FDA as of September 1, 2022. We extracted the therapeutic classification from the WHO ATC system. We conducted a descriptive analysis of the data. Result(s): The FDA listed 86 drugs including 72 active ingredients and 14 combinations with a boxed warning mentioning renal toxicity. Three drugs had emergency use authorizations for COVID-19, and all combinations included metformin. There were 8 (8.7%) drugs with renal toxicity boxed warnings approved before 1970, 6 (6.5%) in the 1970s, 14 (15.2%) in the 1980s, 34 (37.0%) in the 1990s, 17 (18.5%) in the 2000s, 9 (9.8%) in the 2010s, and 4 (4.3%) in 2020-Sep 2022. The therapeutic classes with the largest number of renal toxicity boxed warning included anti-infectives for systemic use 24 (26.1%), antineoplastic and immunomodulating agents 22 (23.9%), and alimentary tract and metabolism 17 (18.5%). The most common boxed warnings included renal impairment (n=21, 22.8%), nephrotoxicity (10, 10.9%), and nephrogenic systemic fibrosis (7, 7.6%). Additionally, 9 (9.8%) boxed warnings referred to the potential problems for patients with kidney transplants. Conclusion(s): Most drugs with a boxed warning were approved in the 1990s and 2000s. The therapeutic classes with the highest number of renal toxicity warnings were anti-infective for systemic use, antineoplastic and immunomodulating agents, and alimentary tract and metabolism. The most common warnings were renal impairment, nephrotoxicity, nephrogenic systemic fibrosis, and issues for patients with kidney transplants. Future research could expand the analysis to renal toxicity warnings, interactions, and precautions.Copyright © 2023

Teaching biochemistry and metabolism using a YouTube channel during COVID-19 pandemic.

YouTube is a widely recognized video-sharing platform that students often use to search for videos that explain ideas and concepts related to their courses, seminars, or research. With the outbreak of the coronavirus pandemic, education has undergone a dramatic shift toward virtual learning, leading to a surge in the number of YouTube viewers and video creators. This article discusses the launch of a Spanish-language YouTube channel focused on biochemistry and metabolism, which was found to be useful by the author's students enrolled in Nutritional Biochemistry course at Universidad Científica del Sur, Lima Perú. This innovation has also benefited students and teachers across Peru and other Spanish-speaking countries. Based on this experience, teachers and professionals should be encouraged to share their knowledge on this platform, making it a reliable source of information during challenging situations.

Cellular Alterations in Carbohydrate and Lipid Metabolism Due to Interactions with Nanomaterials.

Nanoparticles (NPs) have unique physicochemical properties that are useful for a broad range of biomedical and industrial applications; nevertheless, increasing concern exists about their biosafety. This review aims to focus on the implications of nanoparticles in cellular metabolism and their outcomes. In particular, some NPs have the ability to modify glucose and lipid metabolism, and this feature is especially interesting to treat diabetes and obesity and to target cancer cells. However, the lack of specificity to reach target cells and the toxicological evaluation of nontargeted cells can potentially induce detrimental side effects, closely related to inflammation and oxidative stress. Therefore, identifying the metabolic alterations caused by NPs, independent of their application, is highly needed. To our knowledge, this increase would lead to the improvement and safer use with a reduced toxicity, increasing the number of available NPs for diagnosis and treatment of human diseases.

The CH24H metabolite, 24HC, blocks viral entry by disrupting intracellular cholesterol homeostasis.

Cholesterol-24-hydroxylase (CH24H or Cyp46a1) is a reticulum-associated membrane protein that plays an irreplaceable role in cholesterol metabolism in the brain and has been well-studied in several neuro-associated diseases in recent years. In the present study, we found that CH24H expression can be induced by several neuroinvasive viruses, including vesicular stomatitis virus (VSV), rabies virus (RABV), Semliki Forest virus (SFV) and murine hepatitis virus (MHV). The CH24H metabolite, 24-hydroxycholesterol (24HC), also shows competence in inhibiting the replication of multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 24HC can increase the cholesterol concentration in multivesicular body (MVB)/late endosome (LE) by disrupting the interaction between OSBP and VAPA, resulting in viral particles being trapped in MVB/LE, ultimately compromising VSV and RABV entry into host cells. These findings provide the first evidence that brain cholesterol oxidation products may play a critical role in viral infection.

Tuberculosis and Hiv Infection - So Many Questions Pending

Since the early days of HIV infection, back in the eighties, TB - particularly extrapulmonary TB emerged as one of the opportunistic infections affecting these patients, specifically as a reactivation of latent TB infections. A diagnosis of TB in the context of HIV infection was then considered as an 'AIDS defining condition' according to classification systems used at that time. It has been recognized for a long time that there are many interactions between HIV and Mycobacterium tuberculosis, which lead to further immune deterioration and to worsening of both conditions due to complex biological and mechanistic interactions between these two agents. Many methods and techniques have been proposed in order to improve diagnosis of TB in HIV-infected subjects, knowing that TB is the most frequent opportunistic infection;and, if not treated in a timely fashion, it may easily take the lives of affected patients. It is not easy to have a diagnosis of TB in HIV-infected subjects, because of the difficulties for obtaining adequate sputum samples, or because of lack of adequate facilities for making a timely diagnosis, particularly in the so-called developing world. On the other hand, extrapulmonary TB is most frequently found in HIV-infected individuals compared to non-infected subjects, and its diagnosis poses significant difficulties, since so many times invasive procedures must be performed in order to obtain an adequate tissue sample and then be able to identify the pathological characteristics of tuberculous disease. In the first days of HIV infection when no antiretroviral therapy was available, a diagnosis of TB was made on clinical grounds, considering a history of contact or some characteristics of the disease, and those of us who are old (or experienced) enough offered antituberculosis therapy for these subjects, obtaining an adequate response many times, but in all cases, the natural history of HIV infection took place, and ultimately these patients died because of the occurrence of another opportunistic infection (or malignancy). With the advent of antiretroviral therapy in the late nineties, another problem occurred. The possibility of drug-drug interactions, taking into account hepatic metabolism of rifampin and the alterations of antiretroviral drug blood - or tissue - concentrations. On top of this, the occurrence of IRIS became another problem, and strategies and protocols have been designed in order to establish the adequate timing of antituberculosis therapy and sometime later antiretroviral therapy. A last point to be considered is the COVID-19 pandemic. The question to be asked is what the influence of the pandemic has been for affecting TB and HIV diagnosis and therapy strategies and programs, particularly in the developing world, knowing that health systems in these countries have many limitations, and that - scant - resources had to be dedicated for the fight against the pandemic.Copyright © 2023