Life-Threatening Interaction Between Complementary Medicines: Cyanide Toxicity Following Ingestion of Amygdalin and Vitamin C

2005 ◽  
Vol 39 (9) ◽  
pp. 1566-1569 ◽  
Author(s):  
Jonathan Bromley ◽  
Brett GM Hughes ◽  
David CS Leong ◽  
Nicholas A Buckley
Keyword(s):  
Vitamin C ◽  
Probability Scale ◽  
Cyanide Poisoning ◽  
Severe Lactic Acidosis ◽  
Complementary Medicines ◽  
Cyanide Toxicity ◽  
Patients With Cancer ◽  
Case Summary ◽  
Life Threatening

OBJECTIVE: To describe a case of severe accidental cyanide poisoning following a single ingestion of amygdalin with therapeutic intent. CASE SUMMARY: A 68-year-old patient with cancer presented to the emergency department shortly after her first dose (3 g) of amygdalin with a reduced Glasgow Coma Score, seizures, and severe lactic acidosis requiring intubation and ventilation. The patient also ingested 4800 mg of vitamin C per day. She responded rapidly to hydroxocobalamin treatment. The adverse drug reaction was rated probable on the Naranjo probability scale. DISCUSSION: Amygdalin and laetrile (a synthetic form of amygdalin) are commonly used as complementary or alternative medicine (CAM) for the treatment of cancer. Vitamin C is known to increase the in vitro conversion of amygdalin to cyanide and reduce body stores of cysteine, which is used to detoxify cyanide. Amygdalin has been used for decades by patients with cancer who are seeking alternative therapies, and severe reactions have not been reported with this dose. An interaction with vitamin C is a plausible explanation for this life-threatening response. CONCLUSIONS: This case highlights the fact that CAMs can produce life-threatening toxicity. This case also adds a further note of caution, namely, the potential for serious interactions between CAMs, particularly where there is no tradition of concomitant use.

Successful Desensitization to Oxaliplatin

2005 ◽  
Vol 39 (5) ◽  
pp. 966-969 ◽  
Author(s):  
Lydia ◽  
Nishan H Fernando ◽  
Hurbert I Hurwitz ◽  
Michael A Morse
Keyword(s):  
White Woman ◽  
Initial Response ◽  
Response To Therapy ◽  
Controlled Environment ◽  
Metastatic Colon Cancer ◽  
Hypersensitivity Reactions ◽  
Platinum Compounds ◽  
Probability Scale ◽  
Case Summary ◽  
Life Threatening

OBJECTIVE: To report the successful desensitization of a patient to oxaliplatin utilizing an 8-hour desensitization regimen in a controlled environment. CASE SUMMARY: A 53-year-old white woman with metastatic colon cancer was receiving oxaliplatin, bevacizumab, and capecitabine every 2 weeks, with a partial response to therapy. On her fifth cycle of this regimen, she experienced diaphoresis, hypotension, nausea, abdominal cramping, and coryza. According to the Naranjo probability scale, oxaliplatin, and not bevacizumab, was the probable cause of the hypersensitivity reaction. The woman continued therapy with capecitabine and bevacizumab, resulting in stable disease. Due to her initial response to the oxaliplatin-based regimen, it was decided to attempt desensitization to oxaliplatin in a controlled, inpatient environment. An 8-hour desensitization schedule was employed, and the patient successfully completed an additional 3 cycles with full-dose oxaliplatin. DISCUSSION: Hypersensitivity reactions to platinum-containing compounds are well described and potentially life threatening. With expanded use of oxaliplatin in various malignancies, an increased number of hypersensitivity reactions will likely be reported. Patients with previous hypersensitivity reactions to carboplatin are at risk for similar reactions to oxaliplatin. We achieved successful desensitization for oxaliplatin using increased concentrations of the drug over an 8-hour period concomitant with oral and intravenous corticosteroids and histamine blockers. CONCLUSIONS: Hypersensitivity reactions to platinum compounds may result in discontinuation of active therapies in patients with metastatic disease. Desensitization to oxaliplatin is possible utilizing this approach.

scholarly journals Fatality from potassium gold cyanide poisoning

2019 ◽  
Vol 12 (7) ◽  
pp. e229947 ◽  
Author(s):  
Elizabeth Harmon ◽  
Jacob Lebin ◽  
David Murphy ◽  
Bjorn Watsjold
Keyword(s):  
Lactic Acidosis ◽  
Potassium Cyanide ◽  
Clinical Findings ◽  
Rapid Decline ◽  
Gold Cyanide ◽  
Cyanide Poisoning ◽  
Severe Lactic Acidosis ◽  
Cyanide Toxicity ◽  
Intentional Ingestion ◽  
Antidotal Therapy

While potassium cyanide poisoning has been well described, the toxicity of potassium gold cyanide is less well understood. This case describes an 84-year-old man who presented after an intentional ingestion of 0.5–1 teaspoons of potassium gold cyanide. Despite antidotal therapy, the patient rapidly developed severe lactic acidosis, multiorgan dysfunction and ultimately expired. While the patient’s clinical findings were consistent with acute cyanide poisoning, a serum cyanide level was below the toxic threshold. Previous reports have suggested that gold toxicity may also contribute to the effects of potassium gold cyanide, and may have played a role in the patient’s rapid decline. In addition to treatment of cyanide toxicity, management of acute gold toxicity should also be considered in potassium gold cyanide ingestion.

Role of vitamin C in gastric cancer

2018 ◽  
Vol 01 (1) ◽  
Author(s):  
Takalkar U Vidyadhar
Keyword(s):  
Gastric Cancer ◽  
Vitamin C ◽  
Gastric Juice ◽  
Oxidative Dna Damage ◽  
Preventive Measure ◽  
Dietary Factors ◽  
Preventive Strategy ◽  
H Pylori

Gastric cancer is a multifactorial disease with complex interplay of environmental and genetic factors. Helicobacter pylori (H. pylori) infestation has been identified as the most important etiological agent in the pathogenesis of gastric cancer. Also, the role of dietary factors that is low consumption of fruits and vegetables have been found to be associated with gastric cancer. Among the dietary factors, antioxidants especially vitamin C has been found to confer the strongest protection against gastric cancer. Its anti-proliferative and pro-apoptotic action has been suggested in vitro. Because of its antioxidant activity, it protects cells against oxidative DNA damage caused by toxic effects of reactive oxygen species. It also inhibits production of carcinogenic N-nitroso compound in the stomach. The person with H. pylori infection has low levels of vitamin C in their gastric juice and levels of vitamin C normalizes on eradication of H. pylori. Vitamin C levels are high in gastric mucosa and gastric juice, sometimes more than that of in plasma. But gastric pathological conditions cause lowered secretion of vitamin C into gastric juice. Effect of H. pylori on vitamin C in gastric juice is reversible and on eradication of H. pylori, it returns to normal level. Hence, eradication of H. pylori and chemoprevention with antioxidant supplementation will be an effective preventive strategy to reduce the incidence of gastric cancer and related mortality. Vitamin C and gastric cancer is an area of potential interest for researchers as a preventive measure. Keywords: Vitamin C, H. pylori, gastric cancer.

scholarly journals Impairing flow-mediated endothelial remodeling reduces extravasation of tumor cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gautier Follain ◽  
Naël Osmani ◽  
Valentin Gensbittel ◽  
Nandini Asokan ◽  
Annabel Larnicol ◽  
...  
Keyword(s):  
Blood Flow ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Metastatic Progression ◽  
Metastatic Dissemination ◽  
Secondary Tumors ◽  
Flow Profiles ◽  
Endothelial Response ◽  
Life Threatening

AbstractTumor progression and metastatic dissemination are driven by cell-intrinsic and biomechanical cues that favor the growth of life-threatening secondary tumors. We recently identified pro-metastatic vascular regions with blood flow profiles that are permissive for the arrest of circulating tumor cells. We have further established that such flow profiles also control endothelial remodeling, which favors extravasation of arrested CTCs. Yet, how shear forces control endothelial remodeling is unknown. In the present work, we aimed at dissecting the cellular and molecular mechanisms driving blood flow-dependent endothelial remodeling. Transcriptomic analysis of endothelial cells revealed that blood flow enhanced VEGFR signaling, among others. Using a combination of in vitro microfluidics and intravital imaging in zebrafish embryos, we now demonstrate that the early flow-driven endothelial response can be prevented upon specific inhibition of VEGFR tyrosine kinase and subsequent signaling. Inhibitory targeting of VEGFRs reduced endothelial remodeling and subsequent metastatic extravasation. These results confirm the importance of VEGFR-dependent endothelial remodeling as a driving force of CTC extravasation and metastatic dissemination. Furthermore, the present work suggests that therapies targeting endothelial remodeling might be a relevant clinical strategy in order to impede metastatic progression.

scholarly journals 2′FL and LNnT Exert Antipathogenic Effects against C. difficile ATCC 9689 In Vitro, Coinciding with Increased Levels of Bifidobacteriaceae and/or Secondary Bile Acids

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 927
Author(s):  
Louise Kristine Vigsnaes ◽  
Jonas Ghyselinck ◽  
Pieter Van den Van den Abbeele ◽  
Bruce McConnell ◽  
Frédéric Moens ◽  
...  
Keyword(s):  
Antimicrobial Effect ◽  
Secondary Bile Acid ◽  
Clostridioides Difficile ◽  
Life Threatening ◽  
Intermediate Time ◽  
Indigenous Microbiota ◽  
Hospital Acquired ◽  
Gut Microbial Community ◽  
Secondary Bile Acids

Clostridioides difficile (formerly Clostridium difficile) infection (CDI) is one of the most common hospital-acquired infections, which is often triggered by a dysbiosed indigenous gut microbiota (e.g., upon antibiotic therapy). Symptoms can be as severe as life-threatening colitis. The current study assessed the antipathogenic potential of human milk oligosaccharides (HMOs), i.e., 2′-O-fucosyllactose (2′FL), lacto-N-neotetraose (LNnT), and a combination thereof (MIX), against C. difficile ATCC 9689 using in vitro gut models that allowed the evaluation of both direct and, upon microbiota modulation, indirect effects. During a first 48 h fecal batch study, dysbiosis and CDI were induced by dilution of the fecal inoculum. For each of the three donors tested, C. difficile levels strongly decreased (with >4 log CFU/mL) upon treatment with 2′FL, LNnT and MIX versus untreated blanks, coinciding with increased acetate/Bifidobacteriaceae levels. Interindividual differences among donors at an intermediate time point suggested that the antimicrobial effect was microbiota-mediated rather than being a direct effect of the HMOs. During a subsequent 11 week study with the PathogutTM model (specific application of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME®)), dysbiosis and CDI were induced by clindamycin (CLI) treatment. Vancomycin (VNC) treatment cured CDI, but the further dysbiosis of the indigenous microbiota likely contributed to CDI recurrence. Upon co-supplementation with VNC, both 2′FL and MIX boosted microbial activity (acetate and to lesser extent propionate/butyrate). Moreover, 2′FL avoided CDI recurrence, potentially because of increased secondary bile acid production. Overall, while not elucidating the exact antipathogenic mechanisms-of-action, the current study highlights the potential of HMOs to combat CDI recurrence, help the gut microbial community recover after antibiotic treatment, and hence counteract the adverse effects of antibiotic therapies.

scholarly journals Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin N. Nelson ◽  
Savannah G. Beakley ◽  
Sierra Posey ◽  
Brittney Conn ◽  
Emma Maritz ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Cryptococcus Neoformans ◽  
Mammalian Cells ◽  
Cysteine Proteases ◽  
Dependent Manner ◽  
Life Threatening ◽  
Opportunistic Fungal Pathogen ◽  
Dose Dependent ◽  
Lysosomal Proteins

AbstractCryptococcal meningitis is a life-threatening disease among immune compromised individuals that is caused by the opportunistic fungal pathogen Cryptococcus neoformans. Previous studies have shown that the fungus is phagocytosed by dendritic cells (DCs) and trafficked to the lysosome where it is killed by both oxidative and non-oxidative mechanisms. While certain molecules from the lysosome are known to kill or inhibit the growth of C. neoformans, the lysosome is an organelle containing many different proteins and enzymes that are designed to degrade phagocytosed material. We hypothesized that multiple lysosomal components, including cysteine proteases and antimicrobial peptides, could inhibit the growth of C. neoformans. Our study identified the contents of the DC lysosome and examined the anti-cryptococcal properties of different proteins found within the lysosome. Results showed several DC lysosomal proteins affected the growth of C. neoformans in vitro. The proteins that killed or inhibited the fungus did so in a dose-dependent manner. Furthermore, the concentration of protein needed for cryptococcal inhibition was found to be non-cytotoxic to mammalian cells. These data show that many DC lysosomal proteins have antifungal activity and have potential as immune-based therapeutics.

scholarly journals Acute pulmonary embolism in COVID-19 patient: a case report of free-floating right heart thrombus successfully treated with fibrinolysis

2020 ◽  
Author(s):  
Fernando Scudiero ◽  
Antonino Pitì ◽  
Roberto Keim ◽  
Guido Parodi
Keyword(s):  
Pulmonary Embolism ◽  
High Risk ◽  
Retrospective Studies ◽  
Right Heart ◽  
Clinical Issue ◽  
Systemic Thrombolysis ◽  
Case Summary ◽  
High Prevalence ◽  
Life Threatening ◽  
Complex Scenario

Abstract Background Despite the fast-growing understanding of the coronavirus disease 2019 (COVID-19), patient management remains largely empirical or based on retrospective studies. In this complex scenario, an important clinical issue appears to be represented by the high prevalence of thromboembolic events, but the data regarding high-risk pulmonary embolism (PE) is still not available. Case summary A patient with COVID-19 developed sudden shortness of breath and hypoxia. Early echocardiographic diagnosis of high-risk PE related to right heart thrombus was performed. Systemic thrombolysis was administered with excellent clinical and haemodynamic response. Discussion Pulmonary thromboembolism is a common occurrence in severe COVID-19 infection. In our experience, systemic thrombolysis proved to be effective and for this reason may be considered for life-threatening PE in COVID-19 patients.

scholarly journals Effect of Adding Resistant Maltodextrin to Pasteurized Orange Juice on Bioactive Compounds and Their Bioaccessibility

Foods ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1198
Author(s):  
Elías Arilla ◽  
Purificación García-Segovia ◽  
Javier Martínez-Monzó ◽  
Pilar Codoñer-Franch ◽  
Marta Igual
Keyword(s):  
Vitamin C ◽  
Antioxidant Capacity ◽  
Bioactive Compounds ◽  
Orange Juice ◽  
Control Sample ◽  
Water Soluble ◽  
In Vitro Digestibility ◽  
Total Phenols ◽  
Resistant Maltodextrin

Resistant maltodextrin (RMD) is a water-soluble and fermentable functional fiber. RMD is a satiating prebiotic, reducer of glucose and triglycerides in the blood, and promoter of good gut health, and its addition to food is increasingly frequent. Therefore, it is necessary to study its potential effects on intrinsic bioactive compounds of food and their bioaccessibility. The aim of this study was to evaluate the effect of adding RMD on the bioactive compounds of pasteurized orange juice with and without pulp, and the bioaccessibility of such compounds. RMD was added at different concentrations: 0 (control sample), 2.5%, 5%, and 7.5%. Ascorbic acid (AA) and vitamin C were analyzed using HPLC, whereas total phenols, total carotenoids (TC), and antioxidant capacity were measured using spectrophotometry. After that, sample in vitro digestibility was assessed using the standardized static in vitro digestion method. The control orange juice with pulp presented significantly higher values of bioactive compounds and antioxidant capacity than the control orange juice without pulp (p < 0.05). RMD addition before the juice pasteurization process significantly protected all bioactive compounds, namely total phenols, TC, AA, and vitamin C, as well as the antioxidant capacity (AC) (p < 0.05). Moreover, this bioactive compound protective effect was higher when higher RMD concentrations were added. However, RMD addition improved phenols and vitamin C bioaccessibility but decreased TC and AA bioaccessibility. Therefore, the AC value of samples after gastrointestinal digestion was slightly decreased by RMD addition. Moreover, orange pulp presence decreased total phenols and TC bioaccessibility but increased AA and vitamin C bioaccessibility.

scholarly journals A stapled peptide mimetic of the CtIP tetramerization motif interferes with double-strand break repair and replication fork protection

2021 ◽  
Vol 7 (8) ◽  
pp. eabc6381
Author(s):  
Anika Kuster ◽  
Nour L. Mozaffari ◽  
Oliver J. Wilkinson ◽  
Jessica L. Wojtaszek ◽  
Christina Zurfluh ◽  
...  
Keyword(s):  
Strand Break ◽  
Amino Acid Residues ◽  
Dna Double Strand Breaks ◽  
Strand Breaks ◽  
Stapled Peptide ◽  
Patients With Cancer ◽  
Peptide Mimetic ◽  
Dna Damaging Agents ◽  
Stalled Replication Forks

Cancer cells display high levels of DNA damage and replication stress, vulnerabilities that could be exploited by drugs targeting DNA repair proteins. Human CtIP promotes homology-mediated repair of DNA double-strand breaks (DSBs) and protects stalled replication forks from nucleolytic degradation, thus representing an attractive candidate for targeted cancer therapy. Here, we establish a peptide mimetic of the CtIP tetramerization motif that inhibits CtIP activity. The hydrocarbon-stapled peptide encompassing amino acid residues 18 to 28 of CtIP (SP18–28) stably binds to CtIP tetramers in vitro and facilitates their aggregation into higher-order structures. Efficient intracellular uptake of SP18–28 abrogates CtIP localization to damaged chromatin, impairs DSB repair, and triggers extensive fork degradation. Moreover, prolonged SP18–28 treatment causes hypersensitivity to DNA-damaging agents and selectively reduces the viability of BRCA1-mutated cancer cell lines. Together, our data provide a basis for the future development of CtIP-targeting compounds with the potential to treat patients with cancer.

Protective effect of vitamin C and lycopene on the in vitro fertilization capacity of sex‐sorted bull sperm by inhibiting the oxidative stress

2020 ◽  
Vol 55 (9) ◽  
pp. 1103-1114
Author(s):  
Pei‐Pei Zhang ◽  
Jing‐Jing Wang ◽  
Chong‐Yang Li ◽  
Hai‐sheng Hao ◽  
Hao‐Yu Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Vitro Fertilization ◽  
Vitamin C ◽  
Protective Effect ◽  
Vitro Fertilization ◽  
Bull Sperm ◽  
Fertilization Capacity
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