Changes in prescribing patterns and resultant disease control after lamotrigine-related adverse drug reactions: A descriptive analysis

Purpose@#This study aimed to describe the desperate situation where the clinician should make decisions to further manage patients having experienced adverse drug reaction (ADR) to lamotrigine that is indicated to not easily controlled neuropsychiatric diseases. @*Methods@#A descriptive analysis was done by thoroughly reviewing medical records of patients who were reported to have ADR to lamotrigine in a regional drug-safety center between 2010 and 2018. @*Results@#Eighty-four cases of lamotrigine-related ADRs occurred in 80 patients. Skin lesions were most commonly observed in 70 cases (83.3%) and 14 cases (16.7%) had severe ADRs. Sixty-three subjects (78.8%) discontinued lamotrigine, while 17 (21.3%) continued it.At the time of discontinuation, 30.0% were prescribed aromatic antiepileptic drugs. Among 4 subjects who were eventually prescribed lamotrigine again after a period of discontinuation, 3 (75.0%) experienced its recurrence. Among patients who had taken alternative medications, the incidence of ADRs was higher in those being prescribed aromatic antiepileptic drugs than in the others being prescribed other than aromatic antiepileptic drugs (P = 0.013). Regarding the control of underlying diseases, as many as 65 (86.7%) and 68 (90.7%) failed to reach maintaining the resolved state from 6 months and 12 months after the substitution, respectively. @*Conclusion@#Patients can be easily trapped between the recurrence of ADRs and the treatment failure to a certain drug like lamotrigine, in which we can hardly find a reasonable alternative to manage them.

Developmental Expression of eNOS in the Rat Renal Vasculature / 대한해부학회지

Nitric oxide (NO) has an important role in maintaining basal renal blood flow (RBF) and glomerular filtration rate (GFR) in the developing kidney. However, renal endothelial NO synthase (eNOS) has not been localized in the developing kidney. The purpose of this study was to examine the expression and localization of eNOS in the developing rat kidney using immunohistochemistry and western blotting. Kidneys from 14 (E14)-, 16 (E16)-, 18 (E18)- and 20-day-old (E20) fetuses, 1 (P1)-, 4 (P4)-, 7 (P7)-, 14 (P14)- and 21-day-old (P21) pups, and adult rats were extracted for immunohistochemistry, and western blot analysis. In the adult rat kidney, eNOS was expressed strongly in the endothelial cells of the arcuate artery and the vascular bundle in the medulla. Endothelial cells of the glomerulus and peritubular capillary network were weakly labeled for eNOS. There was no eNOS immunoreactivity in the uriniferous tubules, including the proximal tubules. In the developing rat kidney, eNOS appeared in the endothelial cells of the capillary network from E14. In the developing glomerular capillary, immunoreactivity for eNOS was observed in the S-shaped bodies (stage II glomeruli) and stage III glomeruli, whereas mature glomeruli (stage IV glomeruli) were faintly immunolabeled for eNOS. These eNOS-positive early-stage developing glomeruli were observed in the nephrogenic zone until seven days after birth. In the endothelial cells of the peritubular capillary network, eNOS was strongly expressed in the fetus and gradually decreased in intensity after birth. The endothelial cells of the arcuate artery were strongly immunoreactive for eNOS from E16 to the adult stages. In the renal medulla, eNOS was expressed in the endothelial cells of the capillary network surrounding the developing medullary collecting ducts of the fetal kidney. After birth, eNOS immunoreactivity gradually disappeared from the vasculature of the renal medulla and only remained in the vasa recta. In conclusion, the strong expression of eNOS in the early stages of the developing vasculature suggests that eNOS may contribute to angiogenesis and/or critically participate in the hemodynamics of the immature kidney.

Expression of alphasmooth Muscle Actin, Aquaporin 1 and Renin after Blocking AT1 Receptor in Developing Renal Arterial System of Rat / 대한신장학회잡지

BACKGROUND: Recent studies have demonstrated that renin, alphasmooth muscle actin(ASMA) and aquaporin-1(AQP1) participate in the development of renal arterial system. The components of the renin- angiotensin system have been shown to function as growth factors, apart from their classical roles in controlling blood volume and homeostasis. Interestingly, the vasoconstrictor angiotensin II(ANG II) appears to participate in the regulation of angiogenesis in various tissues. The present study examined the effect of ANG II type-1(AT1) receptor blocker losartan given during pregnancy or newborn rats on the expression of renin, ASMA and AQP1 in the developing renal arterial system. METHODS: Pregnant and newborn rats received losartan(10 mg/kg/day) or saline for 4 and 8 days from E14 to parturition, and for 4 and 9 days starting at day 1 after birth, respectively. Kidneys of 17-day-old fetuses and 1-, 4-, and 9-day- old pups were processed for immunohistochemistry using antibodies to renin(1 : 10,000), ASMA(1 : 1,000), and AQP1(1 : 1,000). RESULTS: In all pregnant groups, there were no differences in immunostaining for renin, ASMA, and AQP1 between losartan treated groups and saline treated groups. In all newborn groups, however, blockade of AT1 receptor with losartan found to increase expression of renin and ASMA but to have no effect on expression of AQP1 in the developing renal arterial system. CONCLUSION: These results suggest that AQP1 expression is not associated with renin or ASMA expression during development of renal arterial system.

Developmental Expression of Renin and Aquaporin-1 in the Rat Renal Vasculature / 대한신장학회잡지

Recent studies in the developing rat kidney have demonstrated that renin in juxtaglomerular cells and aquaporin-1(AQP1), a kind of water channel, participate in the development of renal arterial system. The purpose of this study was to identify the association among renin and AQP1 in the developing renal arterial system. Sprague-Dawley rat kidneys from 14-, 16-, 18- and 20-day-old fetuses, and 1-, 4-, 7-, 14-, 21- and 28-day-old pups were preserved with periodate-lysine-2% paraformaldehyde solution for single or multiple immunohistochemistry. Renin- positive, smooth muscle, and endothelial cells were detected using renin polyclonal(1 : 5,000), alpha-smooth muscle actin(ASMA) monoclonal(1 : 1,000), and AQP1 polyclonal(1 : 500) antibodies, respectively. Immunoreactivity for renin and AQP1 was not detected in the developing vessels in fetal kidneys on the 14 th day of gestation. At the 16th day of gestation, AQP1 appeared in the developing kidney. Immunoreactivity for AQP1 was observed in endothelial cells of the arterial capillary plexus and of the arcuate artery, but not in the venous capillary plexus or the arcuate vein. At the 18th day of gestation, renin-positive cells appeared throughout the arterial system including the arcuate artery. After birth, immunoreactivity for renin and AQP1 was gradually decreased in the developing artery. No renin immunoreactivity was detected in the arcuate artery from 7 days after birth, and in the interlobular artery from 14 days after birth. Renin immunoreactivity was confined to juxtaglomerular cells in the afferent arteriole from 21 days after birth. AQP1 immunoreactivity in endothelial cells was not observed in the arcuate artery from right after birth, or in the interlobular artery, or afferent arteriole from 14 days after birth. This study indicates that the expression and loss of AQP1 in endothelial cells spatiotemporally coexists with renin in smooth muscle cells during the development of arterial system in the rat kidney. It is suggested that AQP1 and renin might play an important role in the development and growth of the rat kidney arterial system by functioning through a paracrine or autocrine mechanism.