Urinary zinc excretion and zinc status of patients with Β-thalassemia major

In this study, zinc status and urinary zinc excretion with and without desferrioxamine (DFO) infusion and the relationship between urinary zinc excretion and renal tubular dysfunction in thalassemia major (TM) patients were investigated. Forty TM patients were given four DFO infusions on alternate days over a 1-wk period prior to the transfusion. On each day that DFO was given, a 24-h urine collection initiated. DFO was omitted for 1-wk before the following transfusion and during the period four 24-h urine collections were performed. Twenty healthy children provided 24-h urine collection as controls. Blood samples were taken on each of two consecutive transfusion days of the patients and from the controls. Urinary zinc excretion was measured and plasma and red blood cell (RBC) zinc analysis were performed by inductively coupled plasma-atomic emission spectrophotometry. UrinaryN-acetyl-Β-D-glucosaminidase (NAG) activity and creatinine were determined in morning urine specimens. The mean plasma zinc concentration was significantly lower in the patients not given DFO compared to the values of the patients given DFO and the control group. The mean RBC zinc concentration (Μmol/g Hb) in the patients (with and without DFO) and the control group were similar. Urinary zinc excretion was significantly higher in the patients receiving DFO compared to the control group, whereas urinary zinc excretion in the patients not given DFO was not different from the controls. Urinary NAG indices (U/g Cr) were significantly higher in the patients compared to controls. Urinary zinc excretion was correlated with the urinary NAG indices.     

粉防己碱对豚鼠链霉素性肾损伤的干预作用

研究粉防己碱(Tetrandrine,Tet)对链霉素(Streptomycin,SM)所致的急性肾损伤的干预作用及其保护机制。将双耳ABR阈值≤5dB健康白色红目豚鼠分为(1)正常对照组、(2)Tet组、(3)SM组、(4)SM Tet组,于第11天留取尿标本和肾组织,用浊度法测定尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)活性,用光镜、电镜观察肾组织学改变。形态学检测显示SM Tet组肾脏病理变化比SM组小,凋亡细胞也明显少于SM组。SM Tet组NAG活性比SM组低(P<0.01)。上述结果表明粉防己碱对链霉素所致的急性肾毒性效应有明显的拮抗作用,在药物性器官损伤防护中具有潜在的应用前景。     

A novel immunosuppressant FTY720 ameliorates proteinuria and alterations of intrarenal adrenomedullin in rats with autoimmune glomerulonephritis

FTY720 has been originally developed as a new immunosuppressive agent, which prolongs graft survival in organ transplantation. Adrenomedullin (AM) participates in the regulation of sodium homeostasis and has renoprotective effects. The possible involvement of renal AM in the pathophysiology of glomerulonephritis (GN) and the effect of FTY720 has been evaluated in rats. HgCl2 (1 mg/kg body weight) was inoculated subcutaneously 3 times/week for a total of 2 weeks. FTY720 (3 or 10 mg/kg) was inoculated subcutaneously daily. The proteinuria, urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion and serum total cholesterol levels were increased and serum albumin level was reduced in rats with HgCl2-induced GN compared with controls. FTY720 reduced proteinuria (3 mg/kg: -25%; 10 mg/kg: -41%), urinary NAG excretion (-11%; -52%) and total cholesterol level (-21%; -55%) in a dose-dependent manner. Renal AM level and its mRNA expression were increased in rats with GN compared with controls (Peptide Cortex: +69%; Medulla: +82%; mRNA Cortex: +25%). Interestingly, FTY720 additionally increased these levels (Peptide Cortex: +38%; Medulla: +39%; mRNA Cortex: +20%). Renal AM levels correlated with urinary NAG excretion and creatinine clearance. These results suggest that FTY720 suppresses the renal damage in rats with GN and renal AM may participate in the pathophysiology of GN and the renoprotective effects of FTY720.     

Methylprednisolone favourably alters plasma and urinary cytokine homeostasis and subclinical renal injury at cardiac surgery

Whilst elevated urinary transforming growth factor beta-1 (TGFbeta) is associated with chronic renal dysfunction its role in acute peri-operative renal dysfunction is unknown. In contrast, peri-operative increases in urinary IL-1 receptor antagonist (IL-1ra) and TNF soluble receptor-2 (TNFsr-2) mirror pro-inflammatory activity in the nephron and correlate with renal complications. Steroids modulate some plasma cytokines (decreasing TNFalpha, IL-8, IL-6 and increasing IL-10), whereas ability to reduce plasma and urinary TNFsr-2 and IL-1ra and peri-operative renal injury is unknown. Patients undergoing coronary artery bypass grafting with cardiopulmonary bypass (CPB) were randomised to receive methylprednisolone (n = 18) or placebo (n = 17) before induction of anaesthesia. Plasma and urinary pro- and anti-inflammatory cytokine balance was determined along with subclinical proximal tubular injury and dysfunction, measured by urinary N-acetyl-beta-d-glucosaminidase (NAG)/creatinine and alpha-1-microglobulin/creatinine ratios, respectively. In the control group compared with baseline, plasma IL-8, TNFalpha, IL-10, IL-1ra and TNFsr-2 were significantly elevated along with urinary IL-1ra, TNFsr-2 and TGFbeta1. Urinary NAG/creatinine and alpha-1-microglobulin/creatinine ratios rose from completion of revascularisation until 6 h with recovery at 24 h with a further rise in NAG/creatinine ratio at 48 h. Compared to placebo, the methylprednisolone group showed significantly reduced plasma IL-8, TNFalpha, IL-1ra and TNFsr-2 whereas plasma IL-10 increased. Compared to placebo, the methylprednisolone group demonstrated significantly reduced urinary NAG/creatinine ratio, TNFsr-2 and TGFbeta1 at 24 h whereas urinary alpha-1-microglobulin/creatinine ratios increased. CONCLUSIONS: Methylprednisolone administration during cardiac surgery significantly reduces plasma and urinary TNFsr-2 and IL-1ra, urinary TGFbeta1 and subclinical renal injury but not dysfunction.     

西格列汀对早期2型糖尿病肾病患者肾功能的影响

目的:研究西格列汀对早期2型糖尿病肾病患者肾小球、肾小管标志性蛋白/酶的影响。方法:早期2型糖尿病肾病患者72例,随机数字表分为对照组36例、治疗组36例;两组均采用糖尿病饮食管理、运动治疗,在控制血糖、血脂、血压的基础上,治疗组给予磷酸西格列汀100 mg 1粒/次,1次/天,持续服药6月。观察治疗前、后两组血肌酐(Scr)、尿素氮(BUN)、糖化血红蛋白(Hb A1c)、血脂、空腹血糖(FBG)、餐后2小时血糖(2 h PBG)、血清胱抑素-C(Cys-C)及24 h尿微量白蛋白(24 h UAE)、尿N-乙酰-β-氨基葡萄糖苷酶(NAG)、尿β2-微球蛋白(β2-MG)的变化。结果:治疗后,治疗组血脂、Hb A1c、FBG、2 h PBG较对照组明显下降,差异有显著性(P0.05)。两组患者24 h UAE、NAG、β2-MG和Cys-C较治疗前均下降,差异有显著性(P0.05);两组治疗后相比,差异具有统计学意义(P0.05)。结论:西格列汀可以有效控制早期DN患者的血糖水平,减少血清Cys-C、尿微量白蛋白水平,减轻肾小管损伤,有利于延缓DN的病程和进展。     

The Correlation between Antiesterase Activities and Chemical Structure of Saligenin Cyclic Phosphates

The effect of substituents on phosphorus of saligenin cyclic phosphorus esters on inhibitory activities toward cholinesterases and ali-esterases in vitro and in vivo was studied. The most insecticidal methyl derivative was the strongest inhibitor of insect cholinesterase both in vitro and in vivo. When the size of the substituent increased, the specificity toward ali-esterase increased, while decreased toward cholinesterase. The inhibitor ratio (I₅₀ ChE/I₅₀ AliE) appears to relate closely with insecticidal activity. Non-insecticidal aryl derivatives are very specific to inhibit insect ali-esterase. They are very weak inhibitors of insect cholinesterase in vivo. Their thiono analogs are stronger in vivo than corresponding oxo analogs.     

Release of acid hydrolases in spectrum of human leprosy.

Release of acid hydrolases by blood monocytes (BM) of leprosy patients both before and after 6 months of chemotherapy was measured fluorimetrically. Monocyte cultures were set up for spontaneous as well as zymosan dependent enzyme release measured after 2 hrs and 24 hrs of culture. In the untreated multibacillary group (BL/LL) a significantly higher (P < 0.001) release of both B-glucuronidase (BG) and N-acetyl glucosaminidase (NAG) was observed compared to the paucibacillary group (BT/TT) and healthy controls. On comparing the BT/TT group with controls a significant decrease (P < 0.001) in zymosan dependent NAG release was observed in the former group at 2 hrs culture. After 6 months of antileprosy therapy, a significant decrease (P < 0.05) in BG release was observed from BM of multibacillary patients, whereas NAG activity increased significantly (P < 0.05) in the paucibacillary group compared to the controls. The results of the present study suggest that non-oxidative metabolic status of BM vary within the leprosy spectrum.     

Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats

This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p<0.011; r²>0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.     

Association between urinary indicators of renal dysfunction and metal concentrations in workers chronically co-exposed to cadmium,zinc and lead

The study was carried out in 31 workers co-exposed to cadmium, lead and zinc fumes and dusts in a zinc ore refinery. Urinary cadmium, lead, zinc, β₂-M levels and NAG activities were determined to evaluate the possible dose-effect relationship between these parameters. A correlation was found between urinary cadmium, lead and zinc concentrations, and urinary β₂-M levels and NAG activities of the exposed group. A statistically significant increase was also observed for urinary NAG activity in exposed workers who had urinary cadmium concentrations > 2 μg g^?1 creatinine. However, in the same exposed group, the increment of β₂-M was not statistically significant. In conclusion, the present study thus confirms the earlier observations and may suggest the notion that the urinary NAG seems to be a more sensitive indicator than urinary β₂-M level in early stages of renal injury of moderately cadmium co-exposure with lead and zinc even at urinary cadmium concentration as low as 2 μg g^?1 creatinine. When the earlier studies on the irreversibility of cadmium-induced tubular dysfunction and the present results were taken into consideration, the present health-based biological limit proposed by the WHO (5 μg g^?1 creatinine) seems to be high for the occupational exposure to cadmium.     

Increased urinary zinc excretion in cancer patients is linked to immune activation and renal tubular cell dysfunction

Urinary zinc excretion is known to be increased in cancer patients, but the pathogenesis of this phenomenon remains uncertain. Both skeletal muscle catabolism and renal tubular cell dysfunction have been proposed to explain this observation. We have investigated urinary zinc and N-acetyl--d-glucosaminidase (NAG), an indicator of renal tubular cell dysfunction, as well as serum neopterin, an index of systemic immune activation, in 22 patients with cancer and seven controls. Both serum neopterin and urinary zinc were significantly elevated in cancer patients (15.8 ± 12.7 versus 7.3 ± 2.3 nmol l^–1 and 1.77 ± 0.80 versus 1.21 ± 0.41 mmol mol^–1 creatinine, P < 0 and P < 0.05, respectively), while NAG was similar in cancer patients and the controls (13.58 ± 13.80 versus 13.68 ± 12.19 kat mol^–1 creatinine). A significant correlation was observed between serum neopterin and urine zinc (rs = 0.5119, P < 0.02), serum neopterin and urine NAG (rs = 0.6761, P < 0.002), and urinary zinc and NAG (rs = 0.6348, P < 0.002). In conclusion, the present data indicate a link between urinary zinc excretion and immune activation as well as renal tubular cell dysfunction. In addition, renal tubular cell dysfunction appears to be linked to immune activation.     

Lithium-induced renal toxicity in rats: Protection by a novel antioxidant caffeic acid phenethyl ester

Lithium carbonate used in the long-term treatment of manic-depressive illness has been reported to lead to progressive renal impairment in rats and humans. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygene species mediated oxidative stress in ischemia-reperfusion and toxic injuries. The beneficial effect CAPE on lithium-induced nephrotoxicity has not been reported yet. The purpose of this study was to examine a possible renoprotective effect of CAPE against lithium-induced nephrotoxicity in a rat model. Twenty-two adult male rats were randomly divided into three experimental groups, as follows: control group, lithium-treated group (Li), and lithium plus CAPE-treated group (Li+CAPE). Li were treated intraperitoneally (i.p.) with 25 mg/kg Li₂CO₃ solution in 0.9% NaCl twice daily for 4 weeks. CAPE was co-administered i.p. with a dose of 10 μM/kg/day for 4 weeks. Serum Li, blood urea nitrogen and plasma creatinine, urinary N-acetyl-β-D-glucosaminidase (NAG, a marker of renal tubular injury), and malondialdehyde (MDA, an index of lipid peroxidation), were used as markers of oxidative stress-induced renal impairment in Li-treated rats. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in renal tissue. Serum Li levels were found high in the Li and Li+CAPE groups. In Li-administrated rats, urinary NAG and renal MDA levels were increased according to control and Li+CAPE groups (p < 0.05). CAPE caused a significant reduction in the levels of these parameters. Likewise, renal SOD, CAT and GSH-Px activities were decreased in Li-administrated animals; CAPE caused a significant increase in the activities of these antioxidant enzymes. In conclusion, CAPE treatment has a protective effect against Li-induced renal tubular damage and oxidative stress in a rat model.     

Changes in urinary thromboxane level in man during cardiopulmonary bypass: effect of thromboxane on renal tubules

ONO-3708, a thromboxane A2 (TXA2) antagonist, was administered at a dose of 2 micrograms/kg/min by a double blind method as compared with inactive placebo during cardiopulmonary bypass (CPB) procedure to study the changes of thromboxane B2 (TXB2) levels in plasma and urine and N-acetyl-glucosaminidase (NAG) level in urine. TXB2 levels in plasma and urine increased significantly (P less than 0.01) during CPB in the patients given ONO-3708 (ONO-3708 group) and in those given placebo (placebo group). The plasma TXB2 level as expected from the urinary TXB2 level was higher than the measured plasma TXB2 level showing increases in TXB2 originating from the kidney. The urinary NAG level, increased significantly (P less than 0.01) during CPB the NAG level in ONO-3708 group was significantly low as compared to placebo group. The levels of TXB2 in plasma and urine in ONO-3708 group were not different from those of the patients receiving placebo, indicating that ONO-3708 does not have any effect on TXA2 production. We concluded that the elevation of urinary TXB2 level might be due to increased TXA2 production in the kidney under hypoxic condition induced by hypotension and lowered perfusion during CPB. Furthermore, the increased production of TXA2 appears to suppress the functions of the renal proximal tubules.     

Human parathyroid hormone (1-34) increases urinary excretion of lysosomal enzymes in rats

The kidney is the major target of parathyroid hormone (PTH), and PTH influences the urinary excretion of calcium, phosphate and hydrogen ions. It was previously reported that the urinary, excretion of N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme, transiently increases after human PTH (hPTH) (1-34) infusion in normal subjects and idiopathic hypoparathyroidism patients, but not in pseudohypoparathyroidism type I patients. Here we report that intravenous infusion of hPTH(1-34) to rats transiently increased the urinary excretion of various lysosomal enzymes, such as beta-glucuronidase and acid phosphatase as well as NAG. However, it did not affect the urinary excretion of tubular brush border membrane enzymes, i.e. alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl transpeptidase. Human PTH(1-34) dose-dependently increased the urinary excretion of NAG in rats with a peak at 30 min, which returned to a baseline within 60 min. The increase in the urinary NAG excretion caused by hPTH(1-34) positively correlated with the increase in the urinary cAMP excretion (r = 0.844, p < 0.01), and infusion of dibutyryl cAMP at a dose of 20 mg/kg similarly increased the urinary excretion of NAG. These results suggested that the increase in the urinary excretion of lysosomal enzymes caused by hPTH(1-34) may be a functional response to hPTH(1-34) occurring in the renal tubules via PTH signaling pathway.     

微波辐射对肾小管上皮细胞的影响以及金雀异黄素对其保护作用

目的：观察微波辐照对人近端肾小管上皮细胞（HKC）的影响及金雀异黄素对其的保护作用。方法：HKC分为对照组、微波辐照组、金雀异黄素组（n=6）。金雀异黄素组在辐照前2 h用含30μmol/L金雀异黄素的DMEM培养基进行预培养。辐照后24 h留取上清进行乳酸脱氢酶（LDH）、β-N-乙酰氨基葡萄糖苷酶（NAG）活性及丙二醛（MDA）、超氧化物歧化酶（SOD）活性检测。Hoechst 33258染色观察细胞凋亡情况。结果：与对照组比较,微波辐照组上清NAG、LDH活性明显增加（P < 0.01）,金雀异黄素预处理组则较微波辐照组明显下降（P < 0.01）;微波辐照组上清活性也较对照组明显增加（P < 0.01）。Hoechst 33258染色显示,微波辐照可导致较多量的细胞凋亡,而应用金雀异黄素预处理后细胞凋亡的比例均大大减少。微波辐照可大大提高HKC细胞中的MDA含量,SOD活性降低（P< 0.01）,应用金雀异黄素预处理后MDA的含量无明显降低,SOD的活性明显增大（P < 0.01）。结论：微波辐照可导致人近端肾小管上皮细胞出现功能损伤,金雀异黄素对其具有一定的保护作用,可能与其减轻氧化应激损伤、减少细胞凋亡有关。     

Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity in patients with Graves' disease, subacute thyroiditis, and silent thyroiditis: a longitudinal study.

Urinary N-acetyl-beta-D-glucosaminidase (NAG) activity was measured longitudinally in 12 patients with Graves' disease, 5 patients with subacute thyroiditis, and 1 patient with silent thyroiditis, and compared with that of 36 normal controls. The patients with Graves' disease and subacute thyroiditis were treated with anti-thyroid drug (methimazole or propylthiouracil) and prednisolone, respectively. On the other hand, no treatment was given to the patient with silent thyroiditis. Since two patients with Graves' disease clearly showed transient deterioration of the thyroid function during the treatment period, data from these two patients were separately investigated. Urinary levels of NAG in the remaining ten patients with Graves' disease before, 1, 3, 6 and 12 months after the treatment were 15.59 +/- 7.93 (SD), 8.96 +/- 6.82, 4.39 +/- 2.33, 3.46 +/- 2.24, and 3.63 +/- 2.38 U/g.creatinine (g.Cr.), respectively. Those obtained before, 1 and 3 months after the treatment were significantly higher than those of the controls (2.85 +/- 1.12 U/g.Cr.). Free thyroid hormone levels became normal or low 3 months after the treatment. The two Graves' patients mentioned above showed a transient increase in urinary NAG with concomitant changes in free thyroid hormone levels. Urinary NAG levels in the patients with subacute thyroiditis before, 2, 4, and 6 weeks after the treatment were 16.56 +/- 10.97, 6.76 +/- 2.79, 3.14 +/- 0.48 and 3.70 +/- 1.44 U/g.Cr., respectively. Those obtained before and 2 weeks after the treatment were significantly higher than those of the controls. Free thyroid hormones were normal 2 weeks after therapy. Urinary NAG in the patient with silent thyroiditis was 9.60 U/g.Cr. on the first visit and gradually decreased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cholestasis induced nephrotoxicity: The role of endogenous opioids

AimsElevated levels of endogenous opioids play a pivotal role in several deleterious consequences of cholestasis. Renal dysfunction occurs in cholestasis but its exact mechanism is still unknown. In this study, we investigated the role of endogenous opioids in cholestasis induced nephrotoxicity.Main methodsThirty-five rats were divided into five groups. In groups 1 and 2 BDL rats received either daily subcutaneous 20 mg/kg of naltrexone or its vehicle, for 7 days after BDL. In groups 3 and 4, BDL or Sham rats received no injections. In group 5, normal rats received subcutaneous injections of 20 mg/kg/day of naltrexone for 7 days. At the 7th day, 24 h urine was collected to measure urinary N-acetyl-β-D-glucosaminidase (NAG) as an early marker of renal tubular injury. Kidney samples were then collected for light and electron microscopic studies.Key findingsBDL significantly increased NAG activity compared to sham groups. Naltrexone significantly reversed NAG activity to normal levels in BDL animals. Naltrexone treatment in BDL animals also significantly reversed ALT and AST to their normal levels. In light and electron microscopic studies, there were significant structural alterations in BDL samples, which were mostly prevented in naltrexone treated BDL animals.SignificanceSignificant changes in urinary NAG activity and renal morphology of cholestatic rats were reversed by naltrexone treatment. These results suggest a possible role for endogenous opioids in inducing cholestatic nephrotoxicity.     

Actigraphic sleep-wake patterns and urinary 6-sulfatoxymelatonin excretion in patients with Alzheimer's disease

Recent studies suggest melatonin, due to its antioxidant and free-radical- scavenging actions, may play a role in the neuroprotection against amyloid, which is implicated in the pathogenesis of Alzheimer's disease (AD). In this study, we determined urinary 6-sulfatoxymelatonin (aMT6s) excretion together with actigraphic sleep-wake patterns of untreated male patients with AD who lived at home. Results were compared with those obtained from normal age-matched elderly and normal young male subjects. Similar measurements were also performed in another group of patients with AD who were treated with a cholinesterase inhibitor (Donepezil, Aricept). Total 24h aMT6s values were significantly reduced in elderly controls (19.9h ± 5.2 μg/24h), in those with untreated AD (12.7 ± 4.4 μg/24h), and in patients treated for AD (12.4 ± 4.4 μ g/24h) compared with normal young men (32.8 ± 3.1 μ g/24h). A day-night difference in aMT6s was evident in all young controls, in 50% of elderly controls, in only 20% of patients with untreated AD, and in 67% of those with AD receiving Aricept. Sleep quality (expressed as sleep efficiency, wake time, and long undisturbed sleep duration) was better in young and elderly controls compared with the two groups of patients with AD. There was no significant correlation between aMT6s values or sleep patterns and the severity of cognitive impairment in patients with AD. Taken together, these data suggest that disrupted sleep, decreased melatonin production, and partial lack of day-night difference in melatonin secretion were observed equally in normal elderly and in patients with AD. Our results do not permit drawing any conclusion as to whether changes in urinary aMT6s excretion is correlated with disturbed sleep in patients with AD. (Chronobiology International, 18(3), 513-524, 2001)     

泌尿系细菌L型感染致病性临床研究

目的探讨泌尿系反复感染致病菌的发病特点及细菌L型感染的致病性,为临床诊治提供科学依据。方法将127例清洁中段尿培养确诊的反复发作肾盂肾炎患者,根据致病菌分为细菌型组、细菌伴L型组和细菌L型组,健康体检者为对照组,分析4组患者尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、尿视黄醇结合蛋白(RBP)水平变化。结果泌尿系感染各组尿NAG和尿RBP较正常对照组均有不同程度升高,差异有非常显著性(P0.01),单纯细菌L型感染患者较细菌型及细菌伴L型患者稍低,但细菌型、细菌伴L型及细菌L型3组之间差异无显著性(P0.05)。结论细菌L型在泌尿道感染反复发作中占重要地位,泌尿系细菌L型感染具有致病性。     

Plasma and urinary cytokine homeostasis and renal function during cardiac surgery without cardiopulmonary bypass

Cardiopulmonary bypass (CPB) significantly contributes to the plasma pro-inflammatory cytokine response at cardiac surgery. Complementary plasma and urinary anti-inflammatory cytokine responses have been described. The pro-inflammatory cytokines interleukin 8 (IL-8), tumour necrosis factor alpha (TNF-alpha) and interleukin 1beta (IL-1beta) have lower molecular weights than the anti-inflammatory cytokines interleukin 10 (IL-10), interleukin 1 receptor antagonist (IL-1ra) and TNF soluble receptor 2 (TNFsr2) and thus undergo glomerular filtration more readily. In vitro work suggests that proximal tubular cells are vulnerable to pro-inflammatory cytokine mediated injury. Accordingly, this study investigated the hypothesis that cardiac surgery without CPB would not have significant changes in plasma and urinary cytokines and proximal renal dysfunction. Eight patients undergoing coronary artery bypass grafting (CABG) without CPB were studied. Blood and urine samples were analysed for pro- and anti-inflammatory cytokines. Proximal tubular dysfunction was measured using urinary Nu-acetyl-beta-D-glucosaminidase (NAG)/creatinine and alpha(1)-microglobulin/creatinine ratios. Plasma IL-8, IL-10, IL-1ra and TNFsr2 were significantly elevated compared with baseline. Urinary IL-1ra and TNFsr2 were significantly elevated, as were urinary NAG/creatinine and alpha(1)-microglobulin/creatinine ratios. Two hours following revascularization, urinary IL-1ra correlated with urinary alpha(1)-microglobulin/creatinine ratios (P<0.05). As previously reported in CABG surgery with CPB, we now report that non-CPB cardiac surgery also has significant changes in plasma and urinary cytokine homeostasis and early proximal tubular injury. The correlation between urinary IL-1ra and alpha(1)-microglobulin/creatinine ratios is consistent with earlier suggestions of a mechanistic link between cytokine changes and proximal tubular dysfunction. The relative roles of CPB and non-CPB processes in producing inflammation still require definition.     

Development of a urinary biomarker for exposure to the organophosphate propetamphos: data from an oral and dermal human volunteer study.

Propetamphos is a member of the vinyl phosphate group of insecticides and is mainly used for sheep dipping. There have been no published metabolic studies on the effect of propetamphos in man to date, although the present authors have published the identification of a metabolite. The present paper presents data from a human volunteer study investigating the toxicokinetics of the organophosphorus pesticide propetamphos following oral and dermal exposure. Five volunteers ingested a propetamphos dose of 10 micrograms kg-1 (35 nmol kg-1) body weight. Following a washout of 4 weeks, a 100 mg (356 mumol) dermal dose of propetamphos was applied, occluded to 80 cm2 of the inner forearm, for 8 h to the same five volunteers. In a pilot study (several weeks before the main study), one volunteer also received an occluded dermal dose of 50 mg (178 mumol) propetamphos. Unabsorbed propetamphos on the skin was washed off after 8 h and collected. Blood and urine samples were collected over 30 and 54 h for the oral and dermal exposures respectively. Blood samples were analysed for plasma and erythrocyte cholinesterase. Urine samples were analysed for a urinary metabolite of propetamphos: methylethylphosphoramidothioate (MEPT). Following oral and dermal exposure, peak urinary MEPT levels occurred at 1 and 10-12 h respectively. The apparent urinary elimination half-lives of MEPT had means of 1.7 h (oral exposure) and 3.8 h (dermal exposure). Approximately 40% of the oral dose and 1% of the dermal dose were recovered as urinary MEPT or metabolites, which could be hydrolysed to MEPT. Approximately 90% of the dermal dose was recovered from the skin washings. Data from a volunteer showed that a doubling of the dermal dose resulted in approximately double the concentration of total MEPT. Alkaline hydrolysis of urine samples increased the level of MEPT detected after both oral and dermal doses. The increase was greater and statistically significant (p < 0.001, paired t-test) for the dermal dose. This increase in MEPT suggests the presence of other MEPT-containing metabolites or conjugates. The difference in the increase between oral and dermal doses raises the question of a difference in metabolism between the two routes. No individual showed a significant depression compared with their pre-exposure levels of erythrocyte acetyl cholinesterase or plasma cholinesterase activity for either dosing route. However, on a group basis, there was a statistically significant mean depression in plasma cholinesterase activity at 8 and 24 h for oral exposure, with a maximum mean depression of 7% from pre-exposure levels at 8 h. Hydrolysis of urine samples had the effect of reducing the interindividual coefficient of variation (CV) for total excretion of MEPT following both oral (CV reduced from 36 to 8%) and dermal (CV reduced from 40 to 17%) exposure. The ability to detect and follow the elimination of low doses of propetamphos by measurement of 'total' (after hydrolysis) urinary MEPT suggests it is a suitable biomarker of propetamphos exposure. The comparatively short elimination half-lives suggest a strategy for biological monitoring of occupational exposure based on samples collected at the end of the shift.