YAJEM-56893; No of Pages 5 American Journal of Emergency Medicine xxx (2017) xxx–xxx

Contents lists available at ScienceDirect

American Journal of Emergency Medicine journal homepage: www.elsevier.com/locate/ajem

A role of the endothelial nitric oxide system in acute renal colic caused by ureteral stone☆ Emre Bulbul a, Elif Funda Sener b, Nahide Ekici Gunay c, Bahadir Taslidere d, Elif Taslidere e, Serhat Koyuncu f,⁎, Nurullah Gunay g a

Kayseri Training and Research Hospital, Department of Emergency Medicine, Kayseri, Turkey Erciyes University, Faculty of Medicine, Department of Medical Biology, Kayseri, Turkey Kayseri Training and Research Hospital, Department of Clinical Biochemistry, Kayseri, Turkey d Bezmialem Vakif University, Faculty of Medicine, Department of Histology and Embryology, İstanbul, Turkey e Malatya State Hospital, Department of Emergency Medicine, Malatya, Turkey f Gaziosmanpasa University, Faculty of Medicine, Department of Emergency Medicine, Tokat, Turkey g Erciyes University, Faculty of Medicine, Department of Emergency Medicine, Kayseri, Turkey b c

a r t i c l e

i n f o

Article history: Received 6 February 2017 Received in revised form 1 August 2017 Accepted 1 August 2017 Available online xxxx Keywords: Urinary stone disease Endothelial nitric oxide system Renal colic Emergency department

a b s t r a c t Background and aims: Endothelial nitric oxide synthase gene polymorphisms play a role in some pathophysiological processes. In this study, the possible effects of endothelial nitric oxide synthase gene polymorphisms on ureteral stone disease in patients who were admitted to the emergency department with severe pain due to renal colic are examined. Materials and methods: The study groups were designed as controls and patients. The control group was formed from the healthy volunteers who applied to the blood center next to the emergency service. The patient group comprised patients who were diagnosed with ureteral stone disease with severe pain. All of the genetic studies were based on extracted peripheral blood samples using the necessary procedures from the Genome and Stem Cell Center at Erciyes University (GENKOK). The data were analyzed with SPSS (IBM, ver 20, United Sate). Results: The study group comprised 62 females and 138 males, and the control group comprised 64 females and 136 males. All of the stones that caused renal colic were found to be localized in the ureters and the ureterovesical junction. The genotypes of the intron 4 polymorphism were found to be as follows: 4a/4a in 10 people, 4b/4a in 115, and 4b/4b in 275 people. The GG genotype of the eNOS-G894T polymorphism was found in 108 patients in the study group and in117 of the healthy individuals. There was no statistically significant difference between the two groups regarding these data. Conclusion: Although this study is the first in the literature to examine the relationship between renal colic and endothelial nitric oxide synthase gene polymorphisms, our study demonstrated that no relation was found. © 2017 Elsevier Inc. All rights reserved.

1. Introduction The severe pain of renal colic (RC) caused by urinary stone disease has an occurrence rate of 1–10% for each person per their lives and accounts for 2% of all admittances to the emergency department [1–3]. The stone passing into the ureter produces high intraluminal pressure, which may cause contractions of the smooth muscles of the ureter and induce irritation and obstruction, which hereby produces spasms that lead to unbearable pain [4,5].

☆ There is no conflict of interest between authors of this study. ⁎ Corresponding author at: Gaziosmanpasa University, Faculty of Medicine, Department of Emergency Medicine, 60100 Tokat, Turkey. E-mail address: [email protected] (S. Koyuncu).

Nitric oxide (NO), which is synthesized from L-arginine, has a role in the physiopathology of RC. Because axons and neuronal endings that are positive for neuronal nitric oxide synthase (nNOS) reside in the human ureter, NOS, which participates in the synthesis of NO may be related to RC [6]. The hypothetical relationship between NO and RC is expressed in the hypothesis that NO can cause the progression of a stone to be easier and stiffer with adilatation effect on the ureter where the smooth muscle is located. The possible relationship between RC and endothelial NOS (eNOS), which is a different isoenzyme that is involved in the synthesis of NO that functions in smooth muscle organs such as the ureter, has been left mostly unexplored to this day. Endothelial NOS, which is coded for by a gene that is located on the long arm of the 7th chromosome, has a role in the synthesis of NO, which relaxes the smooth muscles of the gastrointestinal and cardiovascular systems and acts in other pathophysiological processes [7,8]. The few clinical studies of RC and NO

http://dx.doi.org/10.1016/j.ajem.2017.08.008 0735-6757/© 2017 Elsevier Inc. All rights reserved.

Please cite this article as: Bulbul E, et al, A role of the endothelial nitric oxide system in acute renal colic caused by ureteral stone, American Journal of Emergency Medicine (2017), http://dx.doi.org/10.1016/j.ajem.2017.08.008

2

E. Bulbul et al. / American Journal of Emergency Medicine xxx (2017) xxx–xxx

in the literature have mostly focused on the medical treatment of pain caused by RC [9]. However, there are no studies of the possible role of the eNOS isoenzyme in severe pain. We believe that analyzing the role of eNOS, which has a well-known role in inflammation [10], in RC processes will facilitate a better understanding of the pathophysiology of RC. In recent years, many polymorphisms and several mutations located in the exons, introns and promoter regions of the gene that codes the eNOS enzyme have been described. These mutations are known to cause some structural and functional changes in gene expression and the eNOS enzyme and therefore lead to changes in NO levels These eNOS gene polymorphisms have roles in pathophysiological processes, such as essential hypertension, coronary heart disease, polycystic kidney disease, and cerebrovascular disease [11,12]. In this study, the possible effects of eNOS gene polymorphisms in patients who were admitted to the emergency department with severe pain due to RC were examined.

diagnosis. Computed tomography was used in cases with suspected aortic pathologies and in female patients with obstetric/gynecologic pathologies if ultrasonography produced unsatisfactory results [15]. This algorithm for the diagnosis of RC is the routine workup in our emergency department, and no new laboratory or radiological testing was applied. Age, sex, medical history, family history, complaints secondary to pain, and the presence of fever, blood pressure, cardiac pulse, and respiratory rate abnormalities of the RC patients were recorded. Additionally, serum levels based on laboratory testing of these patients were kept in the patients' charts, and the names, dosages, and administration routes of drugs used to treat RC were recorded. Of these criteria, kidney transplantation, postrenal acute kidney failure and severe infections were reasons for the exclusion of patient from present study. However, their treatment was continued in accordance with the most recent guidelines. The same procedures were followed while obtaining samples from the control group. Subjects with histories of major trauma or operations, systemic disease and the chronic use of medications were excluded.

2. Materials and methods 2.1. Patient selection and assessment of the study groups Two groups were formed to conduct the study. First, the patient group consisted of patients who were diagnosed with RC in the emergency department. Second, the control group was established from healthy breeders and blood donors from a blood center associated with the emergency department. This study was conducted with the collaboration of the Department of Emergency Medicine and the Department of Medical Biology of Erciyes University Medical Faculty. The study was approved by the local ethical committee (date May 9th, 2014. No: 2014/286) and supported by a project (TTU-2015-5634) from the Scientific Research Projects Department of Erciyes University, Kayseri, Turkey. The main inclusion criterion was an age over 18 years and a proven diagnosis of RC. Patients under the age of 18 were not included in the study, mainly because the pediatric population, other than the trauma patients, is not referred to our emergency department. RC patients with systemic diseases, chronic use of medication, and acute renal failure were excluded. Moreover, pregnancy and evident infection were other reasons for exclusion. All of the RC patients were treated for their RC and underlying pathology by an attending physician in emergency medicine. Moreover, a senior resident in emergency medicine informed the subjects and obtained their verbal and written consent. All patients admitted to the emergency department with complaints that were possibly related to RC, such as pain radiating from the groin, testicular or vaginal complaints without side pain, nausea/vomiting accompanied by colic pain, or complaints related to the urinary tract, were evaluated for inclusion [13]. After physical examinations, this population was examined with basic urine testing, plain radiograms of the urinary systems, and ultrasonography. RC was diagnosed according to the presence of a stone on ultrasonographic testing with or without pelvicalyceal ectasia and the presence of no other signs that caused suspicion of different pathologies [14]. Even in cases in which a stone was observed on a plain radiogram, all patients were further tested with ultrasonography because we use plain radiograms only for differential

2.2. Sample preparation and genotyping studies of the eNOS gene polymorphisms All of the genetic studies were performed at the Genome and Stem Cell Center at Erciyes University (GENKOK). Two-milliliter blood samples with EDTA were obtained from each patient and control. Genomic DNA was extracted from the peripheral blood samples using the standard procedures of High Pure PCR Template Preparation Kit (Roche, Germany). The final DNA concentrations were determined with a NanoDrop 2000 spectrophotometer (Thermo Scientific). Amplifications of the eNOS intron 4 polymorphism (rs61722009) were performed using standard polymerase chain reaction (PCR). The PCR products were visualized on a 2% agarose gel stained with ethidium bromide [16]. The eNOSGlu298Asp (894G NT, rs1799983) polymorphism was identified using a PCR-restriction fragment length polymorphism (RFLP)-based protocol. The PCR products were checked on 2.5% agarose gel, and the 206-bp eNOS product was digested overnight at 37 °C with Mbo I (Thermo Scientific, USA) restriction endonuclease enzyme [17, 18]. The genotyping of the eNOS-786 T/C (rs2070744) polymorphism was determined by the PCR-RFLP method using the Msp I restriction enzyme at 37 °C for 16 h (Thermo Scientific, USA). The restriction fragments were separated by electrophoresis on a gel composed of 3% agarose. All of the PCR methods are summarized in Table 1.

2.3. Statistical analysis The data obtained in our study were analyzed with SPSS (IBM, ver 20, United State). Categorical variables were tested with the chi-square test. Numerical variables were analyzed with the Shapiro-Wilk's test. Multiple comparisons were performed with ANOVA analysis. The strengths of the relationships between the numerical variables were tested with Pearson correlation analyses. Statistical significance was accepted at p b 0.05.

Table 1 Primer sequences and PCR Program for genotyping eNOS gene polymorphisms. eNOS gene polymorphisms

PCR primers

Annealing TEMPERATURE (oC)

PCR product (bp)

Restriction enzyme

Intron 4 (4a/4b) (rs61722009)

F: 5′- AGGCCCTATGGTAGTGCCTT-3′ R: 5′- TCTCTTAGTGCTGTGGTCAC-3’ F: 5′- CATGAGGCTCAGCCCCAGAAC- 3′ R: 5′- AGTCAATCCCTTTGGTGCTCAC- 3′ F: 5′- AGGCCCTATGGTAGTGCCTT-3′ R: 5′- TCTCTTAGTGCTGTGGTCAC-3′

56

420



60

206

MboI

60

180

Msp I

894GNT (rs1799983) −786 TNC (rs2070744) F: Forward; R: Reverse; bp: base pairs.

Please cite this article as: Bulbul E, et al, A role of the endothelial nitric oxide system in acute renal colic caused by ureteral stone, American Journal of Emergency Medicine (2017), http://dx.doi.org/10.1016/j.ajem.2017.08.008

E. Bulbul et al. / American Journal of Emergency Medicine xxx (2017) xxx–xxx Table 2 Percentage of cardinal complaints at the time of admission for patients.

Table 4 Localization of stones in study group.

Complainta

n

%

Side pain Nausea Groin pain Sense of burn during urination Color change of urine

182 104 122 96 46

91 52 61 48 23

a

3

Proximal ureter Midportion of ureter Distal ureter Ureterovesical junction

n

%

29 18 68 85

15 9 34 42

There is no complaint in control group.

3. Results 3.1. Study and control groups The study group consisted of 62 females and 138 males, and the control group consisted of 64 females and 136 males. The mean ages of the participants in the study and control groups were 38.16 ± 14.4 and 38.29 ± 14.7, respectively. There were no statistically significant differences between the groups in the sex or age categories (p = 0.986 and p = 0.457, respectively). The main complaints at the time of admittance were found to be side pain in 182 (91%) patients, groin pain in 122 (61%), nausea in 104 (52%), dysuria and/or pollakiuria and similar urinary problems in 96 (48%) and macroscopic hematuria in 46 (23%). These data are summarized in Table 2. The systolic blood pressure was measured at 164 ± 13 (140–200) mm Hg, and the diastolic blood pressure was 108 ± 6.3 (95–125) mm Hg. The mean arterial pulse was recorded as 104 ± 12 (95–120)/min. The mean respiratory rate was calculated at 26 ± 4/min. In 186 patients (83%), the respiratory rate was over 20 per minute. These data are summarized in Table 3. Laboratory workups of the study group revealed hematuria in 162 (81%) patients, leukocyturia in 52 (26%), and proteinuria in 40 (20%). The presence of a stone in the ureter was diagnosed with plain radiograms in 38 (19%) patients, with ultrasonography in 122 (61%) patients, and with computed tomography in 194 (97%) patients. Patients with indirect or non-clear signs of RC due to a stone were excluded from the study. The stone-caused signs and symptoms were found to be localized in the proximal ureter in 29 (15%) patients, in the middle ureter in 18 (9%) patients, in the distal ureter in 68 (34%) patients, and in the ureterovesical junction in 85 (42%) patients (Table 4). Patients with stones in the kidney, bladder, or urethra were not included. The sizes of the stones ranged from smaller than 5 mm in 85 (42%) patients, 5– 10 mm in 70 (35%) patients, 10–20 mm in 28 (14%) patients, and larger than 20 mm in 17 (9%) patients. Additionally, unilateral and bilateral pelvicalyceal ectasia were detected in 21 (11%) and three cases, respectively.

Table 3 Vital signs of patient and control groups.

Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Pulse rate (per minute) Respiratory rate (per minute) Blood urea nitrogen (mg/dL) Creatinine (mg/dL) Calcium (mg/dL) Sodium (mmol/L) Potassium (mmol/L) Aspartate aminotransferase (U/L) Alanine aminotransferase (U/L) Total bilirubin (mg/dL) Amilase (U/L)

Patient group Mean ± SD

Control group Mean ± SD

164 ± 13

138 ± 28

108 ± 6.3

98 ± 16

104 ± 8.1 26 ± 3.6 14 ± 3.8 0.7 ± 0.56 9.2 ± 0.33 138 ± 3.4 4.3 ± 0.7 14.4 ± 2.3 8.1 ± 1.2 0.25 ± 0.2 37 ± 4.6

100 ± 18 24 ± 2.6 13.2 ± 2.7 0.8 ± 0.45 9.4 ± 0.65 140 ± 4.2 4.4 ± 0.5 16 ± 4.9 12 ± 3.7 0.28 ± 0.03 33 ± 2.1

The mean blood urea nitrogen (BUN) and the mean creatinine values were found to be 14 ± 3.8 [8–23]mg/dL and 0.7 ± 0.56 (0.5– 0.9) mg/dL, respectively. Other biochemical workups revealed the blood calcium, potassium, sodium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), amylase, and bilirubin levels to be 9.2 ± 0.33 (8.8–10.2) mg/dL, 4.3 ± 0.73 (5–5.5) mmol/L, 38 ± 3.4(136– 145) mmol/L, 14.4 ± 2.3 (0−32) U/L, 8.1 ± 1.2 (0−33) U/L, 37 ± 4.6 (28–100) U/L and 0.25 ± 0.2 (0–0.9) mg/dL, respectively. These results exhibited no statistically significant differences between the groups (Table 3). In 156 unresponsive patients, treatment was continued with fentanyl (1 microgram/kg) that was slowly intravenously administered. Third-tier treatment with pethidine (1 mg/kg) was used in 42 cases. The only patient in our study who was unresponsive to all drug therapy was a male patient with several bilateral stones located from the renal pelvis to the penis, and this patient eventually required hospitalization (Diagram 1). Other than this specific patient, 44 (22%) cases with stones larger than 10 mm, 21 cases (11%) with severe unilateral pelvicalyceal ectasia, and 3 cases (2%) with severe bilateral pelvicalyceal ectasia were hospitalized in the urology department. 3.2. Genetic analysis The genotypes of the intron 4 polymorphism were found to be as follows: 4a/4a in 10 people, 4b/4a in 115, and 4b/4b in 275 people. Of the participants with the 4a/4a genotype, 6 were from the study group, and 4 were from the control group. Of the participants with the 4b/4a genotype, 61 were from the study group, and 140 were from the control group. Of the participants with the 4b/4b genotype, 140 were from the study group, and 135 were from the control group. There were no statistically significant differences between the groups (p = 0,852). The GG genotype of the eNOS-G894T polymorphism was found in 108 patients with RC (48%) and 117 healthy individuals (52%). The TT genotype was found in 10 patients with RC (42%) and in16 healthy individuals (58%). The GT genotype was observed in 82 patients with RC (54%) and in 69 healthy individuals (46%). Statistical analyses revealed no significant differences between groups regarding the eNOS-G894T polymorphisms (p = 0.342). Of the three genotypes of the eNOS-786 TN C polymorphism, 83 patients (48%) and 90 individuals from the control group (52%) carried the TT genotype. Ninety-five patients (51%) and 90 individuals from the control group (49%) carried the TC genotype. Twenty-two patients (52%) and 20 individuals from the control group (48%) carried the CC genotype. There were no statistically significant differences between the two groups regarding the eNOS3-786 T N C polymorphism (p = 0.774; Table 5). 4. Discussion RC accounts for 2% of all admittances to the emergency department and presents with severe pain as the cardinal symptom. The multifactorial etiology of RC renders family history as an important factor [19–22], and this key point guided us to plan this genetic study. Each individual in the patient group was carefully selected after excluding all differential diagnoses. The patient distribution included a female/male ratio of 62/138, a mean age of 38, and a most common complaint of side pain (91%), and these findings are concordant with the data in the literature [23–25]. Because we believe that basic urine testing, plain radiograms,

Please cite this article as: Bulbul E, et al, A role of the endothelial nitric oxide system in acute renal colic caused by ureteral stone, American Journal of Emergency Medicine (2017), http://dx.doi.org/10.1016/j.ajem.2017.08.008

4

E. Bulbul et al. / American Journal of Emergency Medicine xxx (2017) xxx–xxx

Table 5 Gender and genotype distributions of the groups. Variables

Patients (n = 200) (%)

Controls (n = 200) (%)

p value

Gender Male Female

138(51) 62 (49)

136 (49) 64 (51)

0,457

eNOS intron 4 4b/4b 4b/4a 4a/4a

140 (51) 54 (47) 6 (60)

135 (49) 61(53) 4 (40)

0.852

eNOS G894T GG GT TT

108 (48) 82 (54) 10 (42)

117 (52) 69 (46) 16 (58)

0.342

90 (52) 90 (49)

0.774

eNOS-786T NC TT 83 (48) TC 95 (51)

elicit a new chapter in the diagnosis of this condition and may facilitate prophylactic drug use. The prevalence of RC is increasing, and RC recurs in 50% of patients 10 years after the initial RC attack. In the year 2000, RC and urinary stone disease cost the United States' health system 2.1 billion dollars [21,33]. This burden on both individuals and national health systems proves the importance of this clinical entity for which more studies are needed.

Acknowledgments This study was supported by the Scientific Research Project Department of Erciyes University (TTU-2015-5634). References

ultrasonography, blood biochemistry, and the sizes and location of the stones were not relevant to the hypothesis of our study, we do not discuss these results in this article. However, we believe two topics may be important to discuss. First, we prospectively examined and interpreted the vital signs of the RC patients at the time of their admittance to the emergency department. Although not reviewed in detail in the literature, most clinicians are aware that pain due to RC may cause sympathetic hyperactivity that leads to abnormalities in vital signs. We believe that the prospective nature of this study is valuable regarding ureter stones, which are known to be the most painful of their type. In other words, patients with RC due to ureter stones have high systolic and diastolic blood pressure and increased cardiac pulse and respiratory rates. These nonspecific findings may be important factors in the differential diagnosis. Another common group of patients with abdominal pain is patients with bleeding into the abdominal cavity. These patients may be prone to low blood pressure; thus, this difference may save valuable time for medical teams [26–28]. Second, we would like to discuss the relatively high rate of computed tomography that was ordered in the diagnoses of the study group. This choice is not specific to the current study; recent literature suggests that ultrasonography may have limited value, and computed tomography may be the best choice of diagnostic tools unless contraindicated by pregnancy [29]. We believe this situation indicates that recent medical practice tends to trust laboratory and radiological tools instead of anamnesis and physical examinations. Nevertheless, although it was not a methodological choice, the high rate of computed tomography due to its high sensitivity to ureter stones promoted standardization in our study. Endothelial NO that is synthesized by eNOS gene from L-arginine is an important neurotransmitter in the genito-urinary system that controls smooth muscles by secreting vasoactive mediators. The presence of the L-arginine/NO metabolic pathway for urethral smooth muscle relaxation has previously been immunohistochemically demonstrated. Therefore, we hypothesized that polymorphisms of this gene's structure may be related to the occurrence of RC [30,31]. Moreover, previous genetic studies have revealed the relationships of eNOS gene polymorphisms with essential hypertension and erectile dysfunction [32]. The statistical analyses of the polymorphisms of intron 4a/4b, eNOS786 T N C, and eNOS- G894Tthat were examined in our study that consisted of 200 patients with RC and 200 healthy individuals revealed no statistically significant differences. Although a large number of individuals, i.e., 400 subjects, were examined in our study, other polymorphisms of the eNOS gene, which were not the focus of our study, may be related to RC. However, this study is the first in the literature to examine the relationship between RC and eNOS genotypes. We plan to expand this study by focusing on other polymorphisms and also by examining eNOS gene expression. We believe this field of study is a valuable addition to the literature because any significant relation may

[1] Valerio M, Doerfler A, Chollet Y, Schreyer N, Guyot S, Jichlinski P. Emergency management of renal colic. Rev Med Suisse Dec 2 2009;5(228):2457–61. [2] Moran CP, Courtney AE. Managing acute and chronic renal stone disease. Practitioner Feb 2016;260(1790):17–20 [12-13]. [3] Gunaydin GP, Dogan NO, Cevik Y, Korkmaz H, Savrun A, Cikrikci G. Evaluation of patients with renal colic that present to an emergency department during the month of Ramadan. Journal of Academic Emergency Medicine 2013;12(1):24. [4] Giamberardino MA. Visceral pain model, kidney stone pain. Encyclopedia of Pain. Berlin Heidelberg: Springer; 2013. p. 4186–90. [5] Makanjuola JK, Rintoul-Hoad S, Bultitude M. Evolving guidance on ureteric calculi management in the acute setting. Curr Urol Rep Mar 2016;17(3):24. [6] Kariman H, Majidi A, Taheri S, Shahrami A, Hatamabadi HR. Analgesic effects of inhalation of nitric oxide (Entonox) and parenteral morphine sulfate in patients with renal colic; a randomized clinical trial. Bull Emerg Trauma Apr 2015;3(2): 46–52. [7] Lanas A. Role of nitric oxide in the gastrointestinal tract. Arthritis Res Ther 2008;10 (Suppl 2:S4). [8] Sticchi E, Fatini C, Gensini F, Battaglini B, Liotta AA, Abbate R. High-speed detection of the G894T polymorphism in exon 7 of the eNOS gene by real-time fluorescence PCR with the light-cycler. Biochem Genet Apr 2004;42(3–4):121–7. [9] Levent A, Buyukafsar K. Expression of Rho-kinase (ROCK-1 and ROCK-2) and its substantial role in the contractile activity of the sheep ureter. Br J Pharmacol Oct 2004; 143(3):431–7. [10] Forstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J Apr 2012;33(7):829–37 (837a–837d). [11] Fedele F, Mancone M, Chilian WM, Severino P, Canali E, Logan S, et al. Role of genetic polymorphisms of ion channels in the pathophysiology of coronary microvascular dysfunction and ischemic heart disease. Basic Res Cardiol Nov 2013;108(6):387. [12] Yagita Y, Kitagawa K, Oyama N, Yukami T, Watanabe A, Sasaki T, et al. Functional deterioration of endothelial nitric oxide synthase after focal cerebral ischemia. J Cereb Blood Flow Metab Oct 2013;33(10):1532–9. [13] Serinken M, Karcioglu O, Turkcuer I, Ozkan HI, Keysan MK, Bukiran A. Analysis of clinical and demographic characteristics of patients presenting with renal colic in the emergency department. BMC Res Notes 2008;1:79. [14] Pfau A, Eckardt KU, Knauf F. Diagnosis and treatment of nephrolithiasis. What is established? Internist (Berl) Dec 2015;56(12):1361–8. [15] Turk C, Petrik A, Sarica K, Seitz C, Skolarikos A, Straub M, et al. EAU guidelines on diagnosis and conservative management of urolithiasis. Eur Urol Mar 2016;69(3): 468–74. [16] Sener EF, Emirogullari ON, Serhatlioglu F, Ozkul Y. The role of endothelial nitricoxide synthase gene G894T and intron 4 VNTR polymorphisms in hemodialysis patients with vascular access thrombosis. Anadolu Kardiyol Derg May 2014;14(3):239–43. [17] Kocyigit I, Taheri S, Sener EF, Unal A, Eroglu E, Ozturk E, et al. Effect of both angiotensin converting enzyme and endothelial nitric oxide synthase genes polymorphisms and expressions on hypertension in autosomal dominant polycystic kidney disease. Cardiorenal Medicine 2014;4(3–4):269–79. [18] Taslidere B, Sener EF, Taslidere E, Gunay NE, Bol O, Bulbul E, et al. Role of the endothelial nitricoxide synthases system on acuteappendicitis. Turkish Journal of Trauma and Emergency Surgery 2016;22(4):338–43. [19] Cevik Y, Corbacioglu SK, Cikrikci G, Oncul V, Emektar E. The effects of Ramadan fasting on the number of renal colic visits to the emergency department. Pak J Med Sci Jan-Feb 2016;32(1):18–21. [20] Lavergne O, Bonnet Q, Thomas A, Waltregny D. How I treat. a renal colic. Rev Med Liege May 2016;71(5):220–6. [21] Golzari SE, Soleimanpour H, Rahmani F, Zamani Mehr N, Safari S, Heshmat Y, et al. Therapeutic approaches for renal colic in the emergency department: a review article. Anesth Pain Med Feb 2014;4(1):e16222. [22] Perez JA, Palmes ML, Ferrer JF, Urdangarain OO, Nunez AB. Renal colic at emergency departments. Epidemiologic, diagnostic and etiopathogenic study. Arch Esp Urol 2010;63(3):173–87. [23] Beltrami P, Guttilla A, Ruggera L, Bernich P, Zattoni F. Renal colic, where is it headed? An observational study. Arch Ital Urol Androl Mar 2016;88(1):7–12. [24] Shirazi M, Salehipour M, Afrasiabi MA, Aminsharifi A. Analgesic effects and safety of desmopressin, tramadol and indomethacin in patients with acute renal colic; a randomized clinical trial. Bull Emerg Trauma Apr 2015;3(2):41–5.

Please cite this article as: Bulbul E, et al, A role of the endothelial nitric oxide system in acute renal colic caused by ureteral stone, American Journal of Emergency Medicine (2017), http://dx.doi.org/10.1016/j.ajem.2017.08.008

E. Bulbul et al. / American Journal of Emergency Medicine xxx (2017) xxx–xxx [25] Leveridge M, D'Arcy FT, O'Kane D, Ischia JJ, Webb DR, Bolton DM, et al. Renal colic: current protocols for emergency presentations. Eur J Emerg Med Feb 2016;23(1): 2–7. [26] Borghi L, Meschi T, Guerra A, Briganti A, Schianchi T, Allegri F, et al. Essential arterial hypertension and stone disease. Kidney Int Jun 1999;55(6):2397–406. [27] Sinha Y. Elderly patient with ureteric colic: suspect leaking aneurysm. BMJ Case Rep 2013;2013. [28] Nicolau C, Claudon M, Derchi LE, Adam EJ, Nielsen MB, Mostbeck G, et al. Imaging patients with renal colic-consider ultrasound first. Insights Imaging Aug 2015; 6(4):441–7. [29] Ozden E, Gogus C, Turkolmez K, Yagci C. Is fluid ingestion really necessary during ultrasonography for detecting ureteral stones? A prospective randomized study. J Ultrasound Med 2005;24:1651–7.

5

[30] Cekmen MB, Turgut M, Turkoz Y, Aygun AD, Gozukara EM. Nitrik Oksit (NO) ve Nitrik Oksit Sentaz (NOS)'ınFizyolojik ve Patolojik Özellikleri. Türkiye Klinikleri Pediatri Dergisi 2001;10(4):226–35. [31] Grange RW, Isotani E, Lau KS, Kamm KE, Huang PL, Stull JT. Nitric oxide contributes to vascular smooth muscle relaxation in contracting fast-twitch muscles. Physiol Genomics Feb 7 2001;5(1):35–44. [32] Gur S, Kadowitz PJ, Gurkan L, Chandra S, Dewitt SY, Harbin A, et al. Chronic inhibition of nitric-oxide synthase induces hypertension and erectile dysfunction in the rat that is not reversed by sildenafil. BJU Int Jul 2010;106(1):78–83. [33] Hong DY, Kim JW, Lee KR, Park SO, Baek KJ. Epidemiologic and clinical characteristics of patients presenting with renal colic in Korea. Urol J May-Jun 2015;12(3):2148–53.

Please cite this article as: Bulbul E, et al, A role of the endothelial nitric oxide system in acute renal colic caused by ureteral stone, American Journal of Emergency Medicine (2017), http://dx.doi.org/10.1016/j.ajem.2017.08.008

A role of the endothelial nitric oxide system in acute renal colic caused by ureteral stone.

Endothelial nitric oxide synthase gene polymorphisms play a role in some pathophysiological processes. In this study, the possible effects of endothel...
279KB Sizes 3 Downloads 26 Views