Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
February-2022 Volume 23 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
February-2022 Volume 23 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Treatment of patients with Covid‑19 with a high dose of ulinastatin

  • Authors:
    • Hai Huang
    • Ping-Fang Hu
    • Liang-Liang Sun
    • Yi-Bin Guo
    • Qiong Wang
    • Zhi-Min Liu
    • Ji-Zhong Yin
    • Pei-Mei Shi
    • Zong-Li Yuan
    • Wei-Fen Xie
  • View Affiliations / Copyright

    Affiliations: Department of Pulmonary and Critical Care Medicine, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Department of Endocrinology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China, Department of Health Statistics, Second Military Medical University, Shanghai 200433, P.R. China
    Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 121
    |
    Published online on: December 7, 2021
       https://doi.org/10.3892/etm.2021.11044
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Currently, there are no specific therapeutic agents available for the treatment of coronavirus disease 2019 (Covid‑19). The present study aimed to assess the efficacy of high‑dose ulinastatin for the treatment of patients with Covid‑19. A total of 12 patients hospitalized with confirmed severe acute respiratory syndrome coronavirus 2 infection were treated with a high dose of ulinastatin alongside standard care. Changes in clinical manifestations, laboratory examinations and chest images were retrospectively analyzed. A total of 10 patients with severe Covid‑19 and two patients with moderate Covid‑19 received ulinastatin treatment. The average age of the patients was 68.0±11.9 years (age range, 48‑87 years). In total, nine of the 12 patients (75.0%) had one or more comorbidities. The most common symptoms on admission were fever (8/12, 66.7%), cough (5/12, 41.7%) and dyspnea (5/12, 41.7%). The percentage of lymphocytes was decreased in 41.7% of patients (5/12) and 58.3% of patients (7/12) had elevated hypersensitive C‑reactive protein (CRP) levels (mean, 49.70±77.70 mg/l). The white blood cell levels and the percentage of lymphocytes returned to normal in all of the patients, and CRP was significantly decreased and returned to normal in 83.3% of patients (10/12; mean, 6.87±6.63 mg/l) on day 7 after ulinastatin treatment. Clinical symptoms were relieved synchronously. The peripheral oxygen saturation improved and 66.7% of the patients (8/12) did not require further oxygen therapy 7 days after ulinastatin treatment. No patients required intensive care unit admission or mechanical ventilation. All patients revealed different degrees of absorption of pulmonary lesions after treatment. Compared with the standard care group, ulinastatin treatment significantly prevented illness deterioration. In conclusion, these preliminary data revealed that high‑dose ulinastatin treatment was safe and exhibited a potential beneficial effect for patients with Covid‑19.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Guan WJ, Ni ZY, Hu Y, Liang WH, Ou CQ, He JX, Liu L, Shan H, Lei CL, Hui DSC, et al: Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 382:1708–1720. 2020.PubMed/NCBI View Article : Google Scholar

2 

Cucinotta D and Vanelli M: WHO declares COVID-19 a pandemic. Acta Biomed. 91:157–160. 2020.PubMed/NCBI View Article : Google Scholar

3 

Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, et al: Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: A single-centered, retrospective, observational study. Lancet Respir Med. 8:475–481. 2020.PubMed/NCBI View Article : Google Scholar

4 

Zhou YW, Xie Y, Tang LS, Pu D, Zhu YJ, Liu JY and Ma XL: Therapeutic targets and interventional strategies in COVID-19: Mechanisms and clinical studies. Signal Transduct Target Ther. 6(317)2021.PubMed/NCBI View Article : Google Scholar

5 

Calina D, Docea AO, Petrakis D, Egorov AM, Ishmukhametov AA, Gabibov AG, Shtilman MI, Kostoff R, Carvalho F, Vinceti M, et al: Towards effective COVID-19 vaccines: Updates, perspectives and challenges (Review). Int J Mol Med. 46:3–16. 2020.PubMed/NCBI View Article : Google Scholar

6 

Nitulescu GM, Paunescu H, Moschos SA, Petrakis D, Nitulescu G, Ion GND, Spandidos DA, Nikolouzakis TK, Drakoulis N and Tsatsakis A: Comprehensive analysis of drugs to treat SARS-CoV-2 infection: Mechanistic insights into current COVID-19 therapies (Review). Int J Mol Med. 46:467–488. 2020.PubMed/NCBI View Article : Google Scholar

7 

Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, et al: Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 130:2620–2629. 2020.PubMed/NCBI View Article : Google Scholar

8 

Cao X: COVID-19: Immunopathology and its implications for therapy. Nat Rev Immunol. 20:269–270. 2020.PubMed/NCBI View Article : Google Scholar

9 

Mehta P, Mcauley DF, Brown M, Sanchez E, Tattersall RS and Manson JJ: HLH Across Speciality Collaboration, UK. COVID-19: Consider cytokine storm syndromes and immunosuppression. Lancet. 395:1033–1034. 2020.PubMed/NCBI View Article : Google Scholar

10 

Yamamoto M, Matsuyama S, Li X, Takeda M, Kawaguchi Y, Inoue JI and Matsuda Z: Identification of nafamostat as a potent inhibitor of Middle East respiratory syndrome coronavirus S protein-mediated membrane fusion using the split-protein-based cell-cell fusion assay. Antimicro Agents Chemother. 60:6532–6539. 2016.PubMed/NCBI View Article : Google Scholar

11 

Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens TS, Herrler G, Wu NH, Nitsche A, et al: SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 181:271–280.e8. 2020.PubMed/NCBI View Article : Google Scholar

12 

Scudellari M: How the coronavirus infects cells-and why delta is so dangerous. Nature. 595:640–644. 2021.PubMed/NCBI View Article : Google Scholar

13 

Lagoo JY, D'souza MC, Kartha A and Kutappa AM: Role of ulinastatin, a trypsin inhibitor, in severe acute pancreatitis in critical care setting: A retrospective analysis. J Crit Care. 45:27–32. 2018.PubMed/NCBI View Article : Google Scholar

14 

Karnad DR, Bhadade R, Verma PK, Moulick ND, Daga MK, Chafekar ND and Iyer S: Intravenous administration of ulinastatin (human urinary trypsin inhibitor) in severe sepsis: A multicenter randomized controlled study. Intensive Care Med. 40:830–838. 2014.PubMed/NCBI View Article : Google Scholar

15 

Ji M, Chen T, Wang B, Chen M, Ding Q, Chen L, Fang Y, Yu X, Chen Y, Wang X, et al: Effects of ulinastatin combined with mechanical ventilation on oxygen metabolism, inflammation and stress response and antioxidant capacity of ARDS. Exp Ther Med. 15:4665–4670. 2018.PubMed/NCBI View Article : Google Scholar

16 

Zhang X, Zhu Z, Jiao W, Liu W, Liu F and Zhu X: Ulinastatin treatment for acute respiratory distress syndrome in China: A meta-analysis of randomized controlled trials. BMC Pulm Med. 19(196)2019.PubMed/NCBI View Article : Google Scholar

17 

National Health Commission of China. Guideline for diagnosis and treatment for novel coronavirus pneumonia (seventh edition). http://www.nhc.gov.cn/yzygj/s7653p/202003/46c9294a7dfe4cef80dc7f5912eb1989.shtml. Accessed March 4, 2020.

18 

Sanders JM, Monogue ML, Jodlowski TZ and Cutrell JB: Pharmacologic treatments for coronavirus disease 2019 (COVID-19): A review. JAMA. 323:1824–1836. 2020.PubMed/NCBI View Article : Google Scholar

19 

Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W and Xiao G: Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 30:269–271. 2020.PubMed/NCBI View Article : Google Scholar

20 

Holshue ML, DeBolt C, Lindquist S, Lofy KH, Wiesman J, Bruce H, Spitters C, Ericson K, Wilkerson S, Tural A, et al: First case of 2019 novel coronavirus in the United States. N Engl J Med. 382:929–936. 2020.PubMed/NCBI View Article : Google Scholar

21 

Lescure FX, Bouadma L, Nguyen D, Parisey M, Wicky PH, Behillil S, Gaymard A, Bouscambert-Duchamp M, Donati F, Le Hingrat Q, et al: Clinical and virological data of the first cases of COVID-19 in Europe: A case series. Lancet Infect Dis. 20:697–706. 2020.PubMed/NCBI View Article : Google Scholar

22 

Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A, Feldt T, Green G, Green ML, Lescure FX, et al: Compassionate use of remdesivir for patients with severe Covid-19. N Engl J Med. 382:2327–2336. 2020.PubMed/NCBI View Article : Google Scholar

23 

Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, et al: A trial of lopinavir-ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. 382:1787–1799. 2020.PubMed/NCBI View Article : Google Scholar

24 

Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, et al: Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet. 395:1054–1062. 2020.PubMed/NCBI View Article : Google Scholar

25 

Guan WJ, Liang WH, Zhao Y, Liang HR, Chen ZS, Li YM, Liu XQ, Chen RC, Tang CL, Wang T, et al: Comorbidity and its impact on 1590 patients with Covid-19 in China: A nationwide analysis. Eur Respir J. 55(2000547)2020.PubMed/NCBI View Article : Google Scholar

26 

Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L, Castelli A, Cereda D, Coluccello A, Foti G, Fumagalli R, et al: Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the lombardy region, Italy. JAMA. 323:1574–1581. 2020.PubMed/NCBI View Article : Google Scholar

27 

Chen Q, Hu C, Liu Y, Liu Y, Wang W, Zheng H, Rong L, Jia J, Sun S, Yu C and Liu YM: Safety and tolerability of high-dose ulinastatin after 2-h intravenous infusion in adult healthy Chinese volunteers: A randomized, double-blind, placebo-controlled, ascending-dose study. PLoS One. 12(e0177425)2017.PubMed/NCBI View Article : Google Scholar

28 

World Health Organization. Clinical management of severe acute respiratory infection (SARI) when COVID-19 disease is suspected. Interim guidance. https://www.who.int/publications-detail/clinical-management-of-severe-acute-respiratory-infection-when-novel-coronavirus-(ncov)-infection-is-suspected. Accessed March 13, 2020.

29 

Linder A and Russell JA: An exciting candidate therapy for sepsis: Ulinastatin, a urinary protease inhibitor. Intensive Care Med. 40:1164–1167. 2014.PubMed/NCBI View Article : Google Scholar

30 

Kanai T, Ishiwata T, Kobayashi T, Sato H, Takizawa M, Kawamura Y, Tsujimoto H, Nakatani K, Ishibashi N, Nishiyama M, et al: Ulinastatin, a urinary trypsin inhibitor, for the initial treatment of patients with Kawasaki disease: A retrospective study. Circulation. 124:2822–2828. 2011.PubMed/NCBI View Article : Google Scholar

31 

Wagner C, Griesel M, Mikolajewska A, Mueller A, Nothacker M, Kley K, Metzendorf MI, Fischer AL, Kopp M, Stegemann M, et al: Systemic corticosteroids for the treatment of COVID-19. Cochrane Database Syst Rev. 8(CD014963)2021.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Huang H, Hu P, Sun L, Guo Y, Wang Q, Liu Z, Yin J, Shi P, Yuan Z, Xie W, Xie W, et al: Treatment of patients with Covid‑19 with a high dose of ulinastatin. Exp Ther Med 23: 121, 2022.
APA
Huang, H., Hu, P., Sun, L., Guo, Y., Wang, Q., Liu, Z. ... Xie, W. (2022). Treatment of patients with Covid‑19 with a high dose of ulinastatin. Experimental and Therapeutic Medicine, 23, 121. https://doi.org/10.3892/etm.2021.11044
MLA
Huang, H., Hu, P., Sun, L., Guo, Y., Wang, Q., Liu, Z., Yin, J., Shi, P., Yuan, Z., Xie, W."Treatment of patients with Covid‑19 with a high dose of ulinastatin". Experimental and Therapeutic Medicine 23.2 (2022): 121.
Chicago
Huang, H., Hu, P., Sun, L., Guo, Y., Wang, Q., Liu, Z., Yin, J., Shi, P., Yuan, Z., Xie, W."Treatment of patients with Covid‑19 with a high dose of ulinastatin". Experimental and Therapeutic Medicine 23, no. 2 (2022): 121. https://doi.org/10.3892/etm.2021.11044
Copy and paste a formatted citation
x
Spandidos Publications style
Huang H, Hu P, Sun L, Guo Y, Wang Q, Liu Z, Yin J, Shi P, Yuan Z, Xie W, Xie W, et al: Treatment of patients with Covid‑19 with a high dose of ulinastatin. Exp Ther Med 23: 121, 2022.
APA
Huang, H., Hu, P., Sun, L., Guo, Y., Wang, Q., Liu, Z. ... Xie, W. (2022). Treatment of patients with Covid‑19 with a high dose of ulinastatin. Experimental and Therapeutic Medicine, 23, 121. https://doi.org/10.3892/etm.2021.11044
MLA
Huang, H., Hu, P., Sun, L., Guo, Y., Wang, Q., Liu, Z., Yin, J., Shi, P., Yuan, Z., Xie, W."Treatment of patients with Covid‑19 with a high dose of ulinastatin". Experimental and Therapeutic Medicine 23.2 (2022): 121.
Chicago
Huang, H., Hu, P., Sun, L., Guo, Y., Wang, Q., Liu, Z., Yin, J., Shi, P., Yuan, Z., Xie, W."Treatment of patients with Covid‑19 with a high dose of ulinastatin". Experimental and Therapeutic Medicine 23, no. 2 (2022): 121. https://doi.org/10.3892/etm.2021.11044
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team