Does expression of substance-P in normal appendices confirm the neuroimmune appendicitis or disprove the negative appendectomy?
Main Article Content
Keywords
Appendicitis, appendectomy, Neuroimmune, neuropeptide, Substance-P expression.
Abstract
Introduction: Detection of specific histological alteration in appendices was carried out using immunohistochemical technique involved using antibodies against a neuropeptide substance-P (s-P).
Methods: Fifty patients aged 3-45 years (21 male and 29 female) admitted to Azadi Teaching Hospital, Kerkuk province, Iraq with clear clinical symptoms of appendicitis.
Results: Significant differences (p≤0.034) was detected at age 11-15 and 16-30 years of patients with clinical suspected appendicitis (CSA) in most patients while right iliac fossa pain (RIFP), vomiting and nausea were predominate clinical symptoms yet non-specific signs of appendicitis. Only 82% appendices appeared inflamed and 18% were normal (without inflammation), were considered as
experimental cases. The intensity and location of the s-P expression was classified as either no expression (negative s-P), weak (+) or strong (++). In experimental cases it was strongly expressed in nerve plexus than in acute inflammation of epithelium and muscularis layers while in lamina propria the expression was almost the same between the two groups. The normal appendices with symptoms
were found without inflammation yet s-P expression was detectable.
Conclusion: Therefore, the stronger expression of s-P in normal appendices may confirm the concept of neuroimmune appendicitis which disproves the negative term of "appendectomy". Further immunehistochemical studies are on to explore specific histological alteration associated with the pains using other antibodies i.e. vasoactive intestinal polypeptide (VIP) and GAP-43.
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appendectomy? The Israel Medical Association Journal (IMAJ); 16(6): 335-337.
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appendicitis in VS children. Pediatric Surgery International; 26(7): 691-696.
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Appendicitis? Time Point Process Mapping in the Emergency Department. Pediatric Emergency Care; Also available at:
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Laboratory Investigation. Supplementum; 234:69-74.
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37. Cho, KJ; Trzaska, KA; Greco, SJ; McArdle, J; Wang, FS; Ye, JH and Rames, P (2005). Neurons Derived From Human Mesenchymal Stem Cells Show Synaptic Transmission and Can Be Induced to Produce the Neurotransmitter Substance P by Interleukin-1α. Stem cells Journals; 23(3): 383-391.
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Laboratory Medicine; 124: 1429-1433.
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47. Payan, D G (1985). Receptor-mediated mitogenic effects of substance P on cultured smooth muscle cells. Biochemical and Biophysical Research Communications; 130: 104-109.
48. Nilsson, J; von Euler, AM and Dalsgaard, CJ (1985). Stimulation of connective tissue cell growth by substance P and substance K. Nature; 315: 61-63.
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arthritis. Science; 235(4791): 893-895.
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52. Weinstock, JV (2015). Substance-P and the regulation of inflammation in infections and inflammatory bowel disease. Acta physiologica; 213(2): 453-461.
53. Suzuki, R; Furuno, T; McKay, DM; Wolvers, D;Teshima, R; Nakanishi, M and Bienenstock, J (1999). Direct neurite-mast cell communication in vitro occurs via the neuropeptide substance P. Journal of Immunology; 163(5): 2410-2415.
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2. Petroianu, A; Barroso, TVV; Buzelin, MA; Bárbara De Melo Theobaldo, BDM and Tafuri, LSDA (2020). Neuroendocrine appendicopathy in morphologically normal appendices of patients with diagnosis of acute appendicitis: Diagnostic study; 60: 344-351.
3. Di Sebastiano, P; Fink, T; Di Mola, FF; Weihe,E; Innocenti, P; Friess, H and Büchler, MW (1999). Neuroimmune appendicitis. Lancet; 354:
461-466.
4. Holzer, P and Holzer-petsche, U (1997). Tachykinins in the gut. Part 2. Roles in neural excitation, Secretion and inflammation. Pharmacology and Therapeutics; 73: 219-263.
5. Gwynn, LK (2001). The diagnosis of acute appendicitis: Clinical assessment versus computed tomography evaluation. Journal of
Emergency Medicine; 21: 119-123.
6. Varadhan, KK; Neal, KR and Lobo, DN (2012). Safety and efficacy of antibiotic compared with appendectomy for treatment of uncomplicated acute appendicitis: meta-analysis of randomized controlled trials. British Medical Journal; 344:1-15.
7. Zoarets, I; Poluksht, N and Halevy, A. (2014). Does selective use of computed tomography scan reduce the rate of "white" (negative)
appendectomy? The Israel Medical Association Journal (IMAJ); 16(6): 335-337.
8. Farmer, DL (2016). Clinical practice guidelines for pediatric complicated Appendicitis: The value in Discipline. Journal of the American Medical Association (JAMA) Surgery; 151(5): 160-193.
9. Lor, DAK (2018). A Bacteriological and histological study of the surgically removed appendix within Kerkuk province. MSc Thesis, Faculty of Science,University of Kerkuk, Iraq.
10. Simpson, J; Samaraweera, AP; Sara, RK and Lobo, DN (2008). Acute appendicitis-a benign disease? Annals of The Royal College of Surgeons of England; 90(4): 313-316.
11. Deng, Y; Chang, DC; Zhang, Y; Webb, J; Gaberkidan, A and Abdullah, F (2010). Seasonal and day of the week variations of perforated
appendicitis in VS children. Pediatric Surgery International; 26(7): 691-696.
12. Bollinger, RR; Everett, ML; Palestrant, D; Love, SD; Lin, SS and Parker, W (2003). Human secretory immunoglobulin A may contribute to biofilm formation in the gut. Immunology; 109:580-587.
13. Bollinger, RR; Barbas, AS; Bush, EL; Lin, SS and Parker, W (2007). Biofilms in the large bowel suggest an apparent function of the human vermiform appendix, Theoretical Biology; 249:826-831.
14. Borley, NR (2005). Vermiform appendix. In:Standing, S; Ellis, H; Healy, JC; Johnson, D;Williams, A and Collins, P. Gray’s anatomy: the
anatomical basis of clinical practice. 39th ed. Edinburgh: Elsevier Churchill Livingstone.
15. Kaminski, A; Liu, IL; Applebaum, H; Lee, SL and Haigh, PI (2005). Routine interval appendectomy is not justified after initial nonoperative treatment of acute appendicitis. Archives of Surgery; 140(9): 897-901.
16. Dasso, JF; Obiakor, H; Bach, H; Anderson, AO and Mage, RG (2000). A morphological and immunohistological study of the human and rabbit appendix for comparison with the avian bursa. Developmental and Comparative Immunology; 24: 797-814.
17. Marniok, B; Slusarczyk, K; Pastuszka, A and Jarosz, R (2004). Anatomical variations of vermiform appendix. Wiadomosci Lekarskie; 57:
156-157.
18. De Coppi, P; Pozzobon, M; Piccoli, M; Gazzola,MV; Boldrin, L; Slanzi, E; Destro, R; Zanesco, L; Zanon, GF and Gamba, P (2006). Isolation of mesenchymal stem cells from human vermiform appendix. Journal of Surgical Research; 135(1):85-91.
19. Feldman, M; Friedman, L and Brandt, L (2016). Sleisenger and Fordtran's Gastrointestinal and Liver Disease Vol.1. 10th ed. ELSIVER. USA. (online Book). Also available at: https://books.google.iq/books?isbn=1455749893
20. Pertroianu, A; Alberti, LR and Zac, RI (2007).Assessment of persistence of fecal loading in the cecum in presence of acute appendicitis. International Journal of Surger; 5: 11-16.
21. Leung, NY; Lau, AC; Chan, KK and Yan, WW (2010). Clinical characteristics and outcomes of obstetric patients admitted to the intensive care unit: a 10 year retrospective review. Hong Kong Medical Journal(HKMJ); 16:18:25.
22. Barker, DJ and Morris, J (1988). Acute appendicitis, bathrooms, and diet in Britain and Ireland. British Medical Journal (Clinical
Research Ed); 296(6627): 953-955.
23. Zangbar, B; Rhee, P; Pandit, V; Hsu, CH; Khalil,M; Okeefe, T; Neumayer, L and Joseph, B (2016). Seasonal Variation in Emergency General Surgery. Annals of Surgery; 263(1): 76-81.
24. Oguntola, AS; Adeoti, ML and Oyemolade, TA (2010). Appendicitis: Trends in incidence, age, sex, and seasonal variations in South-Western Nigeria. Annals of African Medicin; 9(4): 213-217.
25. Abbas, PI; Zamora, IJ; Elder, SC; Brandt, ML;Lopez, ME; Orth, RC; Bisset, GS and Cruz, AT(2016). How Long Does it Take to Diagnose
Appendicitis? Time Point Process Mapping in the Emergency Department. Pediatric Emergency Care; Also available at:
https://www.ncbi.nlm.nih.gov/pubmed/26945196.
26. Sattarova, VI; Eaton, S; Hall, NJ; Lapidus-Krol,E; Zani, A and Pierro, A (2016). Laparoscopy in paediatric surgery: Implementation in Canada and supporting evidence. Journal of Paediatric Surgery; 51(5): 822-827.
27. Petroianu, A; Oliveira-Neto, JE and Alberti, LR (2004). Comparative incidence of acute appendicitis in a mixed population, related to skin color. Arquivos De Gastroenterologia; 41: 24-26.
28. Petroianu, A (2012). Diagnosis of acute appendicitis. International Journal of Surgery;10(3): 115-119.
29. Roulson, J; Benbow, EW and Hasleton, PS(2005). Discrepancies between clinical and autopsy diagnosis and the value of post mortem
histology; A meta-analysis and review. Histopathology; 47(6): 551-559.
30. Whiteside, G and Munglani, R (1998). TUNEL, Hoechst and immunohistochemistry triplelabelling: an improved method for detection of apoptosis in tissue sections-an update. Brain Research. Brain Research Protocols; 3(1): 52-53.
31. Ramos-Vara, JA (2005). Technical Aspects of Immunohistochemistry. Veterinary Pathology; 42: 405-426.
32. Marriott, I (2004). The role of tachykinins in central nervous system inflammatory responses. Frontiers in Bioscience; 9: 2153-2165.
33. Janson, CG (2016). Blocking Borrelia in the brain. Science Translational Medicin; 8: 324.
34. Hökfelt, T; Holmberg, K and Broberger, C (2001). CCK-ergic mechanisms in sensory system. Scandinavian Journal of Clinical and
Laboratory Investigation. Supplementum; 234:69-74.
35. Bazzaz, AA (1983). Studies on the fine structures of primary afferent neurons in the dorsal root ganglia of the Mongolian gerbil, Meriones unguiculatus. PhD Thesis, University of Nottingham, UK.
36. Li, Y; Douglas, SD and Ho, W (2000). Human stem cells express substance-P gene and its receptor. Journal of Hematotherapy and Stem Cell Research; 9: 445-452.
37. Cho, KJ; Trzaska, KA; Greco, SJ; McArdle, J; Wang, FS; Ye, JH and Rames, P (2005). Neurons Derived From Human Mesenchymal Stem Cells Show Synaptic Transmission and Can Be Induced to Produce the Neurotransmitter Substance P by Interleukin-1α. Stem cells Journals; 23(3): 383-391.
38. Xiong, S; Puri, P; Nemeth, L; O’Briain, DS and Reen, DJ (2000). Neuronal hypertrophy in acute appendicitis. Archives of Pathology and
Laboratory Medicine; 124: 1429-1433.
39. Kubota, Y; Petras, RE; Ottaway, CA; Tubbs, RR; Farmer, RG and Fiocchi, C (1992). Colonic vasoactive intestinal peptide nerves in
inflammatory bowel disease. Gastroenterology;102: 1242-1251.
40. Bouchard, S; Russo, P; Radu, A and Adzick, S (2001). Expression of Neuropeptides in Normal and Abnormal Appendices. Journal of Paediatric Surgery; 36(8): 1222-1226.
41. Paterson-Brown, S (2012)."The acute abdomen and intestinal obstruction". In: Garden, OJ; Bradbury, AW; Forsythe, JLR and Parks, RW. Principles and practice of surgery (6th ed.), ELSIVER Churchill Livingstone, China.
42. Van Rossem, C; Treskes, K; Loeza, D and Van Geloven, A (2014). Laparoscopic appendectomy for chronic right lower quadrant abdominal pain.International Journal Colorectal Disease; 29:1199-1202.
43. De Felipe, C; Herrero, JF; O’Brien, JA; Palmer, JA; Doyle, CA; Smith, AJ; Laird, JM; Belmonte, C; Cervero, F and Hunt, SP. (1998). Altered
nociception, analgesia and aggression in mice lacking the receptor for substance P. Nature;392(6674): 394-397.
44. Watson, AHD and Bazzaz, AA (2001). GABA and Glycine-Like Immunoreactivity at Axoaxonic Synapses on la Muscle Afferent Terminals in the Spinal Cord of the Rat. The Journal of Comparative Neurology; 433: 335-348.
45. Xanthos, DN and Sandkuhler, J (2014).Neurogenic neuro-inflammation: inflammatory CNS reactions in response to neuronal activity.
Nature Reviews Neuroscience; 15(1): 43-53.
46. Ho WZ; Lai, JP; Zhu, XH; Uvaydova, M and Douglas, SD (1997). Human monocytes and macrophages express substance P and neurokinin-1 receptor. Journal of Immunology; 159: 5654-5660.
47. Payan, D G (1985). Receptor-mediated mitogenic effects of substance P on cultured smooth muscle cells. Biochemical and Biophysical Research Communications; 130: 104-109.
48. Nilsson, J; von Euler, AM and Dalsgaard, CJ (1985). Stimulation of connective tissue cell growth by substance P and substance K. Nature; 315: 61-63.
49. Lotz, M; Carson, DA and Vaughan, JH (1987). Substance-P activation of rheumatoid synoviocytes: Neural pathway in pathogenesis of
arthritis. Science; 235(4791): 893-895.
50. Bull, HA; Hothersall, J; Chowdhury, N; Cohen, J and Dowd, PM (1996). Neuropeptides induce release of nitric oxide from human dermal microvascular endothelial cells. Journal of Investigative Dermatology; 106: 655-660.
51. O’Connor, TM; O’Connell, J; O’Brien, DI;Goode, T; Bredin, CP and Shanahan, F (2004).The role of substance P in inflammatory disease. Journal of Cellular Physiology; 201:167-180.
52. Weinstock, JV (2015). Substance-P and the regulation of inflammation in infections and inflammatory bowel disease. Acta physiologica; 213(2): 453-461.
53. Suzuki, R; Furuno, T; McKay, DM; Wolvers, D;Teshima, R; Nakanishi, M and Bienenstock, J (1999). Direct neurite-mast cell communication in vitro occurs via the neuropeptide substance P. Journal of Immunology; 163(5): 2410-2415.
54. Goldblum, JR; Lamps, LW; McKenney, JK and Myers, JL (2018). Rosai and Ackerman's In:Surgical Pathology, 11th ed. ELSIVER Inc.
China. (Online Book) Available at:https://books.google.iq/books?isbn=0323442021
55. Paulson, EK; Kalady, MF and Pappas, TN (2003). "Clinical practice. Suspected appendicitis. The New England Journal of Medicine; 348(3): 236-242.
56. Tintinalli, J (2011). Emergency medicine: a comprehensive study guide 7th ed. New York: McGraw-Hill. USA.
57. Barrett, ML; Hines, AL and Andrews, RM (2013). "Trends in Rates of Perforated Appendix, 2001–2010" Statistical Brief -159. Healthcare Cost and Utilization Project (HCUP) Statistical Briefs [Internet]. Rockville (MD): Agency for Healthcare Research and Quality; USA.
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Mar 13, 2023
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Diyari AK Lor, Ayoub A Bazzaz, Noorhan A Chelebi, & Suzanne A Bazzaz. (2023). Does expression of substance-P in normal appendices confirm the neuroimmune appendicitis or disprove the negative appendectomy?. Journal of Population Therapeutics and Clinical Pharmacology, 30(3), 331–345. https://doi.org/10.47750/jptcp.2023.30.03.035
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