Icatibant use in Brazilian patients with hereditary angioedema (HAE) type 1 or 2 and HAE with normal C1-INH levels: findings from the Icatibant Outcome Survey Registry Study

Abstract Background: Hereditary angioedema can be caused by C1-Inhibitor (C1-INH) deficiency and/or dysfunction (HAE-1/2) or can occur in patients with normal C1-INH (HAE nC1-INH). Methods: The Icatibant Outcome Survey (IOS; NCT01034969) registry monitors the safety and effectiveness of icatibant for treating acute angioedema. Objective: Present findings from Brazilian patients with HAE-1/2 and HAE nC1-INH participating in IOS. Results: 42 patients were enrolled (HAE-1/2, n = 26; HAE nC1-INH, n = 16). Median age at symptom onset was significantly lower with HAE-1/2 vs. HAE nC1-INH (10.0 vs. 16.5y, respectively; p = 0.0105), whereas median age at diagnosis (31.1 vs. 40.9y; p = 0.1276) and the median time between symptom onset and diagnosis (15.0 vs. 23.8y; p = 0.6680) were numerically lower vs. HAEnC1-INH, respectively. One icatibant dose was used for > 95% of HAE attacks. Median (range) time-to-event outcomes were shorter for patients with HAE nC1-INH vs. HAE-1/2, including time Study limitations: This was an observational study without a treatment comparator and that relied on patient recall. Conclusions: Findings demonstrate effectiveness and tolerability of icatibant in Brazilian HAE patients.

Expression of Bradykinin Receptors and Effects of Bradykinin in the Interstitial Cells of Cajal from Mouse Small Intestine / 체질인류학회지

Interstitial Cells of Cajal (ICC) are pacemaker cells that generates slow waves and drive spontaneous mechanical contractions of gastrointestinal smooth muscle. Slow waves are generated the periodic activation of spontaneous inward currents (pacemaker currents). We studied the modulation of pacemaker activities by bradykinin (10-8 M) in cultured ICC with the whole cell patch-clamp technique, and the localization of bradykinin-2 receptor-immunoreactivity using double labelling immunohistochemistry in the murine small intestine. Externally applied bradykinin produced membrane depolarization in current-clamping mode. At a -70 mV of holding potential bradykinin increased tonic inward pacemaker currents. Double labelling with bradykinin-2 receptor and and c-kit was shown that ICC expressed the bradykinin-2 receptor-immunoreactivity. These results suggest that bradykinin modulates electrical activities of ICC via bradykinin-2 receptor, which may regulate gastrointestinal motility.

Association of genetic polymorphism of ?_2-bradykinin receptor gene and AGT gene with essential hypertension in Shenzhen population / 第三军医大学学报

Objective To investigate the association between ?_(2)-bradykinin receptor(?_(2)-BKR) gene and angiotensinogen gene polymorphism and essential hypertension.Methods The casecontrol study was conducted using MS-PCR and PCR-SSCP techniques to explore the ?_(2)-BKR gene-58T/C polymorphism and the AGT gene M235T polymorphism in 97 essential hypertensives and 87 normotensives of Shenzhen.Results The genotypes distribution of CC and the alletic frequency of C in EH cases were significantly higher than in controls(0.36 vs 0.14,P=0.000;0.60 vs 0.43,P=0.001).The genotype distributions of CC+MT and TC+MM in EH cases were significantly higher than controls(0.19 vs 0.06,P=0.009;0.18 vs 0.05,P=0.006).The odds ratio for those exposed to CC genotype was 1.913,95% confidence interval was 1.913 to 3.049,P=0.006.No significant difference was seen in the genotype distribution of angiotensinogen gene between EH cases and controls(P=0.091),but the alletic frequency of M in EH cases was significantly higher than controls(0.55 vs 0.44,P=0.037).Conclusion The ?_(2)-BKR gene-58T/C polymorphism might be associated with essential hypertension in Shenzhen population.CC genotype might be associated with the increased risk of EH and C allele might have a gene-gene synergetic effect with M235T polymorphism.