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Herb-Induced Liver Injury by Ayurvedic Ashwagandha as Assessed for Causality by the Updated RUCAM: An Emerging Cause
Get PDFHerb-induced liver injury (HILI) caused by herbal supplements, natural products, and products used in traditional medicine are important for differential diagnoses in patients with acute liver injury without an obvious etiology. The root of Withania somnifera (L.) Dunal, commonly known as ashwagandha, has been used in Ayurvedic medicine for thousands of years to promote health and longevity. Due to various biological activities, ashwagandha and its extracts became widespread as herbal supplements on the global market. Although it is generally considered safe, there are several reported cases of ashwagandha-related liver injury, and one case ended with liver transplantation. In this paper, we review all reported cases so far. Additionally, we describe two new cases of ashwagandha hepatotoxicity. In the first case, a 36-year-old man used ashwagandha capsules (450 mg, three times daily) for 6 months before he developed nausea, pruritus, and dark-colored urine. In the second case, a 30-year-old woman developed pruritus after 45 days of using ashwagandha capsules (450 mg). In both cases, serum bilirubin and liver enzymes (aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were increased. The liver injury pattern was hepatocellular (R-value 11.1) and mixed (R-value 2.6), respectively. The updated Roussel Uclaf Causality Assessment Method (RUCAM) (both cases with a score of seven) indicated a “probable” relationship with ashwagandha. Clinical and liver function improvements were observed after the discontinuation of ashwagandha supplement use. By increasing the data related to ashwagandha-induced liver injury, these reports support that consuming ashwagandha supplements is not without its safety concerns
Uloga NADPH oksidaze i receptora za angiotenzin H tip 2 u razvoju akutne bubrežne slabosti u eksperimentalnoj hipertenziji
No full textAutophagy receptor p62 regulates SARS-CoV-2-induced inflammation in COVID-19
Get PDFIntroduction: Since the interaction between autophagy and virus-induced inflammation is complex,
we investigated the interplay between autophagy and inflammation in COVID-19 patients and THP-1 cells expressing SARS-Cov2 proteins NSP5 and ORF3a. Methods: Autophagy markers in blood from 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric
bead immunoassay. The level of p62 in cells and its concentration in cell culture supernatants
was measured by immunoblot/ELISA. The mRNA levels of proinflammatory cytokines were measured by RT-qPCR.
Results: IFN-α, TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, whereas IL-10 and IL-1β were elevated at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unchanged in COVID-19. The concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission,returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 cells caused an autophagy-independent decrease/autophagy-inhibition-dependent increase of intracellular and secreted p62. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, while a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. Conclusion: The autophagy receptor p62 is reduced in acute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation
Upotreba sokova bogatih polifenolima kao potencijalna prevencija razvoja metaboličkog sindroma i poremećaja vezanih za gojaznost
Get PDFIsolation of Borrelia lusitaniae from the blood of a patient with multiple erythema migrans
Get PDFTropical Diseases of the University Clinical Centre of Serbia with a clinical presentation of disseminated erythema migrans. The patient and the mother could not recall if there had been a tick bite. A sample of blood was taken, and antibiotic therapy with amoxicillin was started immediately. Human serum sample was checked for the presence of IgM antibody against Borrelia burgdorferi sensu lato by commercial ELISA test and the sample was positive for IgM.
Blood was collected into the sterile K2EDTA tube, immediately transported to the Laboratory at the Institute for Medical Research, National Institute of the Republic of Serbia, University of Belgrade, and centrifuged twice at 2200 rpm for 17 min at room temperature. After centrifugation, one part of the serum was served for DNA extraction using ammonium hydroxide, ethanol, and sodium acetate while the sediment was inoculated into a 6 mL tube with Barbour-Stoenner-Kelly-H (BSK-H) medium under aseptic conditions and incubated as 33°C. After 16 days of incubation, viable, motile, and spiral-shaped microorganisms were observed in the initial BSK-H culture under dark-field microscopy, and incubation was prolonged for 29 days. DNA from the culture was extracted using centrifugation, dissolving the sediment in the water, and heating at 95°C for 10 minutes. After extracting DNA from the human serum and the culture, rrf-rrl rDNA intergenic spacer and flagellin gene (flaB) were amplified by conventional PCR, and sequencing of obtained PCR products was performed commercially (Macrogen, Amsterdam, the Netherlands).
After analysis of the sequences obtained, Borrelia lusitaniae was confirmed in human serum and culture. This is the first isolate of B. lusitaniae from a human blood sample that confirms that B. lusitaniae can disseminate via the hematogenous route
Extracellular ATP contributes to erythropoiesis-supportive microenvironment under chronic stress conditions
No full textBackground:
Extracellular adenosine triphosphate (ATP) acts as a signal of disturbed tissue homeostasis and triggers activation
of purinergic receptors, thereby affecting various cellular processes such as proliferation, differentiation, and
migration. Macrophages migrate toward increasing ATP concentrations and possess P2X7 receptors (P2X7R),
which respond to high ATP levels, as well as the ectonucleotidase CD39 that rapidly convert ATP to adenosine
monophosphate. Using a mouse model of psychological stress, we recently demonstrated that macrophages
substantially support erythropoiesis under chronic stress conditions, but the role of extracellular ATP in stressinduced erythropoiesis remains unknown.The Abstract Book of European Hematology Association’s 28th Annual Congress - EHA2023 Hybrid Congress, June 8-15 2023, Frankfurt & Virtua
Effects of Adrenergic Receptor Stimulation on Human Hemostasis: A Systematic Review
No full textCatecholamine stimulation over adrenergic receptors results in a state of hypercoagulability. Chronic stress involves the release and increase in circulation of catecholamines and other stress related hormones. Numerous observational studies in human have related stressful scenarios to several coagulation variables, but controlled stimulation with agonists or antagonists to adrenergic receptors are scarce. This systematic review is aimed at presenting an updated appraisal of the effect of adrenergic receptor modulation on variables related to human hemostasis by systematically reviewing the effect of adrenergic receptor-targeting drugs on scale variables related to hemostasis. By searching 3 databases for articles published between January 1st 2011 and February 16th, 2022 reporting effects on coagulation parameters from stimulation with α- or β-adrenergic receptor targeting drugs in humans regardless of baseline condition, excluding records different from original research and those not addressing the main aim of this systematic review. Risk of bias assessed using the Revised Cochrane risk-of-bias tool for randomized trials (RoB 2). Tables describing a pro-thrombotic anti-fibrinolytic state induced after β-adrenergic receptor agonist stimulation and the opposite after α1-, β-adrenergic receptor antagonist stimulation were synthesized from 4 eligible records by comparing hemostasis-related variables to their baseline. Notwithstanding this low number of records, experimental interventions included were sound and mostly unbiased, results were coherent, and outcomes were biologically plausible. In summary, this systematic review provides a critical systematic assessment and an updated elaboration, and its shortcomings highlight the need for further investigation in the field of hematology
Comprehensive Evaluation of Quality of Life in Penile Cancer Patients following Surgical Treatment
Get PDFBackground: Penile cancer (PC) is a highly aggressive disease, with a significant tendency for lymphatic spreading and subsequent development of distant metastases. The mutilating nature of PC surgical treatment has profound implications on the patient’s body integrity and self-image, sexual life and intimacy, voiding and mental health. The aim of our study was to comprehensively evaluate PC patients’ post-treatment quality of life (QoL), sexual activity, self-esteem, fatigue and fear of disease recurrence. (2) Methods: A cross-sectional study was conducted at the Clinic of Urology, University Clinical Centre of Serbia, and included 31 PC patients. Data were collected by means of a questionnaire. (3) Results: The average score on the Global health status scale was 67.2 out of 100 (ranging from 16.7 to 100), and the SD was 22.5. Hierarchical linear regression analysis showed that demographic characteristics, Hospital Anxiety and Depression scale (HADS) anxiety and depression scores, total Multidimensional Fatigue Inventory, Fear of cancer recurrence and Rosenberg scores and erectile function score explained a total of 78.2% of the variance in the global health status/QoL scale of PC patients. (4) Conclusions: Efforts should be made not only to increase the survival of PC patients after surgical treatment but also to enable the best possible level of QoL in the post-operative period
Hyperbaric oxygen preconditioning in postischemic acute kidney injury: potential mechanisms of beneficial effect
Get PDFCan Transcranial Electrical Stimulation modulate gambling and gaming behaviors?
Get PDFGambling Disorder (GD) and Internet Gaming Disorder (IGD) are formally recognized behavioral addictions with a rapidly growing prevalence and limited treatment options. Recently, transcranial electrical stimulation (tES) techniques have emerged as potentially promising interventions for improving treatment outcomes by ameliorating cognitive functions implicated in addictive behaviors. To systematize the current state of evidence and better understand whether and how tES can influence gambling and gaming-related cognitive processes, we conducted a PRISMA-guided systematic review of the literature focusing on tES effects on risky gambling and gaming behaviors in a diverse range of population samples, including healthy participants, participants with GD and IGD, as well as substance abuse addictions. Following the literature search in three bibliographic databases (PubMed, Web of Science, and Scopus) 40 publications have been included in this review, with 26 conducted on healthy participants, six focusing on GD and IGD patients, and eight including participants with other addictions. Most of the studies targeted the dorsolateral prefrontal cortex using transcranial direct current stimulation (tDCS). The results indicated that tES could change gambling and gaming behaviors and positively influence GD and IGD symptoms. However, the results varied considerably depending on the stimulation parameters, sample characteristics, as well as outcome measures used. We discuss the sources of this variability and provide further directions for the use of tES in the context of GD and IGD treatment