[Show abstract][Hide abstract] ABSTRACT: C-type natriuretic peptide (CNP) selectively binds to the guanylyl cyclase coupled natriuretic peptide receptor (NPR)-B and exerts more potent antihypertrophic and antifibrotic properties. Elimination of CNP occurs mainly by neutral endopeptidase (NEP) and NPR-C.
We established a rat model of unilateral ureteral obstruction (UUO) to examine the continuous change of the CNP expression and to assess the correlations of NPR-B, NPR-C, NEP with CNP in the obstructed kidneys.
The expressions of CNP mRNA and protein in the obstructed kidneys tended to be higher immediately after ligation and declined at later time points compared to sham-operated rats, measured by real-time polymerase chain reaction (PCR) and western blot analysis. Subsequent correlation analysis indicated that CNP mRNA was positively correlated with NPR-B mRNA (r=+0.673, p<0.05). In addition, the increased expression of NPR-C (r=-0.943 and -0.837 for mRNA and protein respectively, p<0.05) and NEP (r=-0.687 and -0.823 for mRNA and protein respectively, p<0.05) were accompanied by a signiﬁcant decline in CNP.
A high level of CNP may contribute to the elevated expression of NPR-B in the early phase of UUO. More interestingly, paradoxical expressions of NPR-C and NEP may account for the decline of CNP in the obstructed kidneys.
Journal of Renin-Angiotensin-Aldosterone System 11/2013; · 2.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Klippel-Trenaunay syndrome (KTS) is a rare and sporadic disorder characterized by the triad of capillary malformations, venous varicosities, and limb hypertrophy. The clinical manifestations of KTS are heterogeneous. In this report, we present a unique case of KTS in combination with congenital dislocation of the hip (CDH) in a 4-day-old female neonate. The patient had a widespread port-wine stain surrounded by regions of unaffected skin in a mosaic pattern, cutaneous hemangioma on the upper lip, left-sided hemihypertrophy involving the entire body, and also evidence of left CDH (based on the results of a physical examination and radiographic interpretation). We present this case for the rarity of presentation, discuss the relationship between KTS and CDH, and the treatment options available with a brief review of the literature.
Journal of the Chinese Medical Association 04/2013; 76(4):229-31. · 0.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The current report detailed an investigation of melamine-linked urinary stones in children exposed to contaminated formula.
A total of 1062 children fed with melamine-contaminated infant formula were screened for urinary stones. Sixty healthy children without melamine exposure were recruited as a control group. Ultrasonography of the urinary tract system was performed. Urinalysis, renal function, liver status, and serum electrolytes were determined.
We encountered 49 affected children from the 1062 screened ones, at a rate of 4.6% per ultrasound performed. Thirty-two were male, and 17 were female. The affected children ranged in age from 1 month to 96 months, with a mean of 25 months. Duration of exposure was from 1.3 months to 84 months, with a mean of 19.5 months. The melamine contents in serum were between 12 mg/kg and 2563 mg/kg, with mean concentration of 1295.3 mg/kg. Most affected children were asymptomatic with no urinary findings. Patients with urinary stones exhibited lower urine pH and serum HCO3 (-) than those in the healthy children, whereas for serum uric acid, alanine aminotransferase, aspartate aminotransferase, and anion gap the opposite trends were observed. The stone diameter ranged from 2 mm to 18 mm with a median of 6.5 mm. Multiple stones were noted in all patients. After 1 week of conservative management, stone diameters of 38 cases (77.6%) were significantly decreased. Among them, urinary stones were discharged completely in 21 affected children (42.9%).
The short-term outcome of melamine-linked urinary stones is satisfactory.
Archives of Medical Science 02/2013; 9(1):98-104. · 1.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study established a simple stereological method to obtain quantitative information about two- or three-dimensional structures based on observations from kidney sections in the unilateral ureteral obstruction(UUO) model. Tubulointerstitial area(TA) and TA/the area of a rectangular field(RA) were raised gradually, but significantly, in the obstructed kidney from 1 to 3months post-ligation in comparison to the sham kidney of sham-operated rats(SOR). On the contrary, glomerular area(GA) and glomerular volume(GV) were decreased progressively over time, but significantly, in the obstructed kidney from 3weeks to 3months post-ligation compared to the sham kidney of SOR. UUO caused a progressive decline of TA and TA/RA in the contralateral kidney. More specifically, there were significant decreases in TA at 1,2,3months post-ligation, while in TA/RA only at 3months post-ligation in comparison to the right kidney of SOR. In contrast, GA and GV enhanced in a time-dependent manner in the contralateral kidney, in which the difference in GA reached significance only at 3months post-ligation, whereas the difference in GV reached significance from 1 to 3months post-ligation when comparing with the right kidney of SOR. Our results confirmed two typical features of obstructive nephropathy, including widen interstitial space and glomerular atrophy in the obstructed kidney, and compensatory growth of the contralateral kidney.
International journal of medical sciences 01/2013; 10(4):385-91. · 2.07 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Neutral endopeptidase (NEP) is the first podocytic antigen responsible for human membranous nephropathy (MN). Besides the prevailing pathogenetic mechanism of immune complex, NEP is also involved in the metabolism of natriuretic peptides (NP). The identification of anti-NEP antibodies in human MN suggests that the decreased circulating NEP may down-regulate the NP catabolism. In this context, we hypothesize that NP disarrangement secondary to anti-NEP antibodies may account, in part, for the onset of proteinuria in MN. Whereas the pathways for the onset of proteinuria caused by elevated NP level are still obscure. The data presented in this review focus on those which support this hypothesis with regards to evidence from the glomerular haemodynamic changes, endothelial permeability, glomerular basement membrane disruption, and podocyte detachment.
[Show abstract][Hide abstract] ABSTRACT: Although the mechanism underlying C-type natriuretic peptide (CNP) beneficial effects is not entirely understood, modulating the expression of matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) may play an important role. The study presented herein was designed as a first demonstration of the regulative effects of CNP on MMPs/TIMPs expression in unilateral ureteral obstruction (UUO) rats. The continuous changes of CNP, MMP-2, MMP-9, TIMP-1, TIMP-2 and type IV collagen (Col-IV) expression were determined in the obstructed rat kidneys at 3 days, 1, 2, and 3 months post-UUO respectively. According to the real-time PCR analysis, CNP, MMP-2 and MMP-9 mRNA expression in the obstructed kidneys were significantly higher compared to every time corresponding SOR, and progressively decreased over time. In contrast, in the obstructed kidneys collected 2 and 3 months post-UUO, the higher TIMP-1 and TIMP-2 mRNA expression were observed in comparison to the corresponding SOR group. The above trends of CNP, MMP-2, MMP-9, TIMP-1, and TIMP-2 transcripts were confirmed by their protein expression based on immunohistochemistry and western blot, and finally contributed to the progressive elevated Col-IV expression in the obstructed kidneys throughout the entire study period. Overexpressed CNP may be an early compensatory response to counteract extracellular matrix remodeling in UUO rats.
[Show abstract][Hide abstract] ABSTRACT: Although recent major advances have developed a much better understanding of the pathophysiological pathways, tubulointerstitial fibrosis (TIF) is still currently incurable. Therefore, early detection may mean that the condition is more manageable than it was in the past. C-type natriuretic peptide (CNP) has been found to be a potent vasodilator but a weak natriuretic factor. In addition, CNP has also been believed to be produced in tubular cells and presented as a local modulator with anti-inflammatory and anti-proliferative effects. Elimination of CNP occurs by three main mechanisms, neutral endopeptidase, natriuretic peptide receptor-C and urinary excretion. Among them, the status of urinary CNP excretion in nephropathies is not yet fully elucidated. In the present study, subgroups of rats were subjected to unilateral ureteral obstruction (UUO) or sham operation and observed for 24h to 3 months. Urinary CNP excretion was significantly enhanced in UUO rats from 24h to 1 month post-ligation compared to sham-operated rats. Urinary CNP excretion was also markedly higher than CNP concentrations both in abdominal aorta and in renal vein, and almost identical concentrations in these two vessels excluded major renal extraction of circulating CNP of systemic origin. Urinary CNP excretion was negatively correlated with urinary protein concentration, blood urea nitrogen and creatinine, while positively correlated with albumin. In conclusion, the increased urinary CNP excretion is strongly associated with TIF progression, and may serve as an early marker of TIF.
[Show abstract][Hide abstract] ABSTRACT: An 11-month-old male infant was admitted to our hospital with fever, fussiness, poor feeding, vomiting, and tachypnea for two days prior. Physical examination revealed sporadic papules and vesicles occurring on his hands, feet, face, and perianal mucosa. Enterovirus 71 was identified from both throat swab and vesicle fluid using virus isolation techniques. The patient's heart rate fluctuated in a very narrow range from 180~210/beats/min regardless of his physiologic state. An electrocardiogram showed P-waves buried within or occurring just after regular, narrow, QRS complexes. The patient was diagnosed as having hand, foot, and mouth disease in combination with paroxysmal supraventricular tachycardia (PSVT). The child recovered well with symptomatic treatment, including intravenous administration of acyclovir, glucocorticoids, immunoglobulin, adenosine, and sotalol. PSVT was terminated within 36 hours of hospitalization. The skin lesions became crusted on the third day, and then proceeded to heal spontaneously. Here we report on this unusual case and review the associated literature.
Annals of Dermatology 05/2012; 24(2):200-2. · 0.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: It is currently believed that melamine ingestion can lead to insoluble crystals in an animal's urinary system with subsequent physical obstruction or bladder carcinoma. However, whether melamine can cause injury of other tissues and organs in humans is yet unknown. In this study, we encountered 3 affected children with liver lesions, 2 males and 1 female, and detailed their clinical characterizations. Their ages were respectively 2, 6, and 10 months. Among the 3 patients with liver lesions, only 1 exhibited symptoms of gradual progressive jaundice, abdominal distention, hepatic intumesce, and bilirubin abnormality; the other 2 were asymptomatic. The mechanism associated with liver lesion may, at least in part, be due to physical deposition and blockage of the biliary tract system. Disturbance of the acid-base equilibrium may be another reason that accelerates stone formation in human tissues.
Archives of Iranian medicine 04/2012; 15(4):247-8. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hypovitaminosis D is highly prevalent in chronic kidney disease (CKD). Recently, vitamin D has sparked widespread interest because of its potential favorable benefits on cardiovascular disease (CVD). Evidence from clinical studies and animal models supports the existence of biphasic cardiovascular effects of vitamin D, in which lower doses suppress CVD and higher doses stimulate CVD. However, the mechanism for the different effects remains unclear. Fibroblast growth factor-23 (FGF-23) is a recently identified member of the FGF family, and thought to be actively involved in renal phosphate and vitamin D homeostasis. More specifically, Vitamin D stimulates FGF-23 secretion and is inhibited by increased FGF-23. Given this background, we hypothesize that FGF-23 may provide a unique tool to explain the biphasic cardiovascular effects of vitamin D in CKD. The data presented in this review support the hypothesis that FGF-23 may be linked with the high cardiovascular risk in CKD through accelerating the onset of vascular calcification, secondary hyperparathyroidism, left ventricular hypertrophy and endothelial dysfunction. Therefore, modulation of FGF-23 may become a potential therapeutic target to lowing cardiovascular risk in CKD. Several clinical interventions, including decreased phosphate intake, phosphate binders, cinacalcet plus concurrent low-dose vitamin D, C-terminal tail of FGF-23 and renal transplantation, have been employed to manipulate FGF-23.
International journal of biological sciences 01/2012; 8(5):663-71. · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While it is true that many traditional cardiovascular risk factors are amenable to intervention in chronic kidney disease (CKD), the results of intervention may not be as efficacious as those obtained in the general population. Thus, there may also be a unique milieu established in CKD, which causes excess cardiovascular disease (CVD) burden by mechanisms that are as yet not fully recognized. Recently, vitamin D has sparked widespread interest because of its potential favorable benefits on CVD. However, the mechanisms for how vitamin D may improve CVD risk markers and outcomes have not been fully elucidated. Furthermore, hypovitaminosis D is highly prevalent in the CKD cohort. Given this background, we hypothesize that low vitamin D status may act as a new CVD risk marker, and modulation of vitamin D signaling may be a potential therapeutic target to lower cardiovascular risk in CKD. The data presented in this review support that the low vitamin D status may be linked with the high cardiovascular risk in CKD, based on both the biological effects of vitamin D itself on the cardiovascular system, and the cross-actions between vitamin D signaling and the multiple metabolic pathways. Considering the high prevalence of hypovitaminosis D, limited natural vitamin D food sources, and reduced sun exposure in CKD patients, recommendations for treatment of hypovitaminosis D mainly focus on exogenous supplementation with vitamin D and its analogues. Although promising, when to start therapy, the route of administration, the dose, and the duration remain need to be discussed.
Medical science monitor: international medical journal of experimental and clinical research 06/2011; 17(6):HY14-20. · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Guangxi Zhuang, the largest ethnic minority in China, is located in the southern part of the country, and well-known to the world as the longevity village. Studies of apolipoprotein E (APOE) polymorphism in adults suggest the lower frequencies of E4 allele and E4/E4 genotype may account, in part, for the favorable lipid profiles of Guangxi Zhuang. However, the effect of APOE polymorphism on serum lipids in the Guangxi Zhuang children is yet unknown to date. In the present study, genomic DNA was extracted from 278 Guangxi Zhuang and 200 Guangxi Han children. APOE genotypes were determined by PCR-restriction fragment length polymorphism (RFLP) analysis. The fasting serum lipoprotein a [Lp(a)], total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1) and apoB were measured. Our results demonstrated that no significant differences in serum lipids were observed between the Guangxi Zhuang and Han children. The E4/E4 and E4/E3 genotypic frequencies were significantly lower in the Guangxi Zhuang children compared with the Guangxi Han children, whereas for E2/E2, E3/E2 and E4/E2 genotypic frequencies the opposite was presented. Though no significant differences in serum lipid concentrations were found for variant alleles both in the Guangxi Zhuang and Han children, the trend was observed in the association of higher levels of Lp(a), TC, TG and LDL-C with E4 allele in the Guangxi Zhuang children. In conclusion, a significant heterogeneity in APOE genetic variation indeed exists between the Guangxi Zhuang and Han ethnic group. The E4 allele may serve as a genetic marker for susceptibility to higher lipid profiles in the Guangxi Zhuang children. Lifestyle should be modified, according to APOE polymorphism even in the young children.
International Journal of Molecular Sciences 01/2011; 12(9):5604-15. · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Apolipoprotein B (apoB) gene 3' variable number tandem repeat (VNTR) is highly variable, and thereby be considered as an informative marker for associative analysis of lipid metabolism.
We conducted this study to probe the effect of apoB 3' VNTR alleles on lipid profiles in 500 Han children from central China, and to compare the allelic distribution of our subjects with multiple Chinese populations. 14 different alleles of the apoB gene 3' VNTR comprising from HVE22 to HVE44 were identified in our subjects.
Allele size distribution followed unimodal curve with the main peak at HVE35 (58.0%). We detected 37 genotypes in this sampling, the most frequently seen was HVE35/35 with a frequency of 36.4%. M/L carriers had significantly higher total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and apoB concentrations than did S/S, M/M or S/M carriers (p<0.05). Individuals with L allele exhibited significantly higher TC, LDL-C, and apoB levels than those with M or S allele (p<0.05). The allelic distribution in Central Han Chinese differed from Southern Han Chinese (X(2)=41.2, p=0.00), Zhuang Chinese (X(2)=65.4, p=0.00), and Uighur Chinese (X(2)=45.6, p=0.00). No significant differences in allelic frequencies were observed for apoB 3' VNTR in Central Han Chinese as compared to Northern Han Chinese (X(2)=2.5, p=0.29).
This study identified the higher repeat alleles as potential risk factor for dyslipidemia in Han children from Central China. Although five Chinese populations demonstrated uniformly unimodal distributions of allelic frequencies with the main peaks at HVE32-HVE37, there was obvious heterogeneity among these populations.
Clinica chimica acta; international journal of clinical chemistry 12/2010; 411(23-24):2092-6. · 2.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A high total plasma cholesterol concentration is the most common abnormality found in patients with kidney disease, which may be associated with the increased hepatic synthesis of apoB containing lipoproteins. ApoB mRNA editing plays an important physiological role in mammalian lipid metabolism by modifying the distribution of apoB-100 and apoB-48. However, it is regretful that apoB mRNA editing cannot be found in human liver because of the absence of apobec-1 expression. In this context, we hypothesize that the recapture of hepatic apoB mRNA editing may be a promising strategy to relieve nephrotic dyslipidemia. The data presented below focus on those which support this hypothesis with regards to evidence in vitro and in vivo. (1) Human wild-type apoB mRNA can be edited only when both apobec-1 and ACF proteins are presented simultaneously in vitro. (2) Adenoviral vectors can produce short-term expression of exogenous apobec-1 in the livers and lower plasma apoB-100 and LDL levels transiently. (3) Apobec-1 transgenic animals exhibit massive hepatic editing of apoB mRNA and fundamental decreased plasma levels of apoB-100 and LDL, but are exposed to high risk of liver dysplasia and hepatocellular carcinomas. In summary, taking into account the therapeutic security, we put forward that apobec-1 recombinant adenoviral vectors can be used for the recapture of hepatic apoB mRNA editing with a transient low-level manner and may achieve satisfactory lipid-lowing effect in nephropathic animals.
Medical Hypotheses 12/2010; 75(6):561-3. · 1.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To detail the utility of CT scan in detection of urinary stones induced by melamine tainted formula.
A total of 1062 children fed with melamine-contaminated infant formula were screened for urinary stones in our institute from September through December 2008. Ultrasonography of the urinary tract system was performed in all these children. If the children with suspected stones or severe obstruction were presented after ultrasound examination, the multi-detector row CT urographic examination was advocated subsequently.
Ultrasound examination in combination with multi-detector row CT urography could increase the diagnostic rate from 3.4% (36/1062) by ultrasound examination alone to 4.6% (49/1062).
The specificity and sensitivity of the multi-detector row CT urographic examination is higher than ultrasonography.
The Indian Journal of Pediatrics 12/2010; 77(12):1405-8. · 0.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Although ATRA is a potent renoprotective agent, relatively little is known regarding the mechanisms of its action. The present study was designed to further elucidate the mechanisms of ATRA's action to GS rats and compare that with the beneficial effect of benazepril. Male SD rats weighting 160 to 200g were used in this study. GS was induced by unilateral nephrectomy and intravenous injection of adriamycin (6mg/kg). They were divided randomly 20 ones per group into GS group, GS treated with ATRA (20mg/kg/day) group, and GS treated with benazepril (10mg/kg/day) group. The other 20 ones were taken as sham-operation group, injected normal saline into caudal vein. 12weeks later, all rats were subjected to sacrifice. As expected, the GS group exhibited significant lower serum TP and Alb, and higher BUN, Cr and proteinuria than those of the sham group. Administration of ATRA or benazepril did ameliorate these above disorders of biochemical parameters in GS rats. Extensive renal damage was observed in the GS group, such as mononuclear infiltration, mesangial proliferation, focal segment glomerular sclerosis, and tubulointerstitial fibrosis. The pathological changes in both ATRA and benazepril group were alleviated remarkably. Semiquantitative GSI was used to evaluate the degree of GS in all groups. GSI was significantly higher in the GS group than in sham group. GSI decreased from 21.9+/-6.7 in the GS group to 6.9+/-2.8 in the ATRA group and 7.0+/-2.7 in benazepril group respectively. However, no significant difference in GSI between rats treated with ATRA and rats treated with benazepril was found. RT-PCR analysis revealed the renal expression of alpha-SMA mRNA was induced substantially in GS group as compared to sham group, which could be offset completely by ATRA or benazepril administration. However, expression level of alpha-SMA mRNA in GS rats treated with ATRA was identical to that in GS rats treated with benazepril. We also examined immunohistochemical staining for renal alpha-SMA, TGF-beta1, Col IV, and FN in this model. Weak staining was observed in some glomerulus, mesangial cells, and tubular interstitium of sham rats. Staining was markedly enhanced in the majority of glomerulus, mesangial cells, and tubular interstitium of untreated GS rats. Compared with untreated GS animals, intensity and extent of staining for renal alpha-SMA, TGF-beta1, Col IV, and FN were markedly reduced in glomerulus, mesangial cells, and tubular interstitium of GS rats treated with either ATRA or benazepril. However, no significant differences existed between ATRA and benazepril with respect to the glomerular and tubulointerstitial staining scores. Interestingly, our data documented some differences of therapeutic capacities between ATRA and benazepril. In comparison with benazepril, ATRA exerted no improvement in hypoproteinemia, but more significant decrease in serum Cr level in GS rats. The reasons leading to these variations are unclear. Whatever they are, the properties of down-regulate inflammatory/proliferative programs may make ATRA an attractive potential candidate for future therapeutic use in kidney disease.
Experimental and Molecular Pathology 08/2010; 89(1):51-7. · 2.13 Impact Factor