Increase In Cys Research Articles

A Non-Immunized and BSA-Template Aggregation-Induced Emission Sensor for Noninvasive Detection of Cystatin C in the Clinical Diagnosis of Diabetes Nephropathy.

Diabetes nephropathy (DN) is one of the main causes of death in patients with diabetes. Cystatin C (Cys C) is a reliable indicator of glomerular filtration function. Therefore, it is urgent and meaningful to obtain early warning of DN by noninvasive measurement of Cys C. In this investigation, a novel fluorescence sensor (BSA-AIEgen sensor) was synthesized by cross-linking the aggregation-induced emission (AIE) characteristics of 2-(4-bromophenyl)-3-(4-(4-(diphenylamino) styryl) phenyl) fumaronitrile (TPABDFN) and bovine serum albumin (BSA), which exhibited the "On" state owing to the restriction of the intramolecular motions (RIM) phenomenon of TPABDFN. Intriguingly, a decrease in fluorescence of BSA-AIEgen sensors could be found owing to BSA on the surface of BSA-AIEgen sensor hydrolyzed by papain, but a reverse phenomenon emerged with the increase of Cys C content as the inhibitor of papain. Hence, Cys C was successfully detected by employing the fluorescent differential display and the linear range was from 12.5 ng/mL to 800 ng/mL (R2 = 0.994) with the limit of detection (LOD) of 7.10 ng/mL (S/N = 3). Further, the developed BSA-AIEgen sensor successfully differentiates patients with diabetes nephropathy from volunteers with the advantages of high specificity, low cost, and simple operation. Accordingly, it is expected to become a non-immunized method to monitor Cys C for the early warning, noninvasive diagnosis, and drug efficacy evaluation of diabetes nephropathy.

Correlation among cystatin C, homocysteine and arteriosclerosis indexes in patients with chronic kidney disease.

Chronic kidney disease (CKD) has become an important public health problem in the world. The occurrence of cardiovascular events is the main cause of death in patients with CKD, and arteriosclerosis is an important pathophysiological basis for cardiovascular diseases. Nowadays, brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI) are clinically important indicators to reflect early atherosclerosis. Cystatin C (Cys C)and homocysteine (Hcy) are related to arteriosclerosis in healthy, hypertensive, and diabetic people, while there are few studies on the correlation among Hcy, CysC and arteriosclerosis in patients with CKD. This study aims to investigate the relationship between Cys C, Hcy and atherosclerosis in patients with CKD. A total of 611 individuals, who met the diagnostic criteria for CKD and underwent physical examination in the Health Management Center of Third Xiangya Hospital, Central South University from June 2019 to June 2020, were selected as the research subjects. Height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured and recorded, and body mass index (BMI) was calculated. Blood samples (5 mL) were collected and Cys C, Hcy, fasting blood glucose (FBG), total cholesterol (TC), serum creatinine (SCr), and other blood indexes were tested. Urine was collected to detect microalbumin and creatinine, and the albumin/creatinine ratio (UACR) was calculated. baPWV and ABI were measured by automatic arteriosclerosis detector. The quartiles of Cys C and Hcy were divided into groups, and the proportion of baPWV and ABI abnormalities among groups was compared pairwise. The correlation between Cys C, Hcy, and baPWV was analyzed by Pearson correlation analysis. Univariate and multivariate logistic regression were used to analyze the effects of Cys C and Hcy on ABI and baPWV. Among 611 patients with CKD, 435 (71.19%) had abnormal baPWV and 48 (7.86%) had abnormal ABI. With the increase of Cys C and Hcy levels, the proportion of baPWV and ABI abnormalities were gradually increased. BaPWV was positively correlated with Cys C (r=0.32) and Hcy (r=0.20). After adjusting for confounding factors such as gender, BMI, and FBG, Cys C (OR=6.54, 95% CI 1.93 to 22.14, P<0.01) and Hcy (OR=1.08, 95% CI 1.01 to 1.16, P=0.02) were independent risk factors for abnormal baPWV. Also, after adjusting for confounding factors such as age, sex, BMI, and FBG, Cys C (OR=9.95, 95% CI 2.84 to 34.92, P<0.01) and Hcy (OR=1.06, 95% CI 1.01 to 1.11, P=0.02) were independent risk factors for abnormal ABI. In patients with CKD, baPWV and ABI are significantly correlated with Cys C and Hcy levels. Detection of Cys C and Hcy levels is helpful for the early diagnosis of arteriosclerosis.

Helically Grooved Gold Nanoarrows: Controlled Fabrication, Superhelix, and Transcribed Chiroptical Switching

Plasmonic chiroptical materials, coupled by chirality and surface plasmons, have been attracting great interest due to their potential applications, such as photonics, chiral recognition, asymmetri...

Microstructure and Mechanical Properties of Powder Thixoforged Amorphous Ni55Nb35Si10-Reinforced Al Matrix Composites

Powder thixoforging was used to produce amorphous Ni55Nb35Si10-reinforced Al matrix composites from recycled Al powders obtained from ball-milled Al520 end-milled billets. The amorphous reinforcing material was uniformly dispersed in the Al matrix and bonded adequately with it without undesired interfacial reactions. The compressive yield strength of composites with 45% reinforcement content increased 248% to 794 MPa over as-cast samples. The maximum elongation and hardness of samples were 15%, and 60.4 HRA, respectively. The relative density of the unreinforced thixoforged sample was 99.8%, indicating near-perfect compaction of Al powders. The maximum elongation, hardness, and compressive yield strength of thixoforged monolithic matrix alloys were, respectively, 40%, 56.9 HRA, and 747 MPa (a 228% increase in CYS over the cast alloy). In contrast, cold-forged samples showed only 82% increase in compressive yield strength over the as-cast alloy. Powder thixoforging introduced in this study—even without reinforcement—delivers better mechanical properties compared to cold forging most likely due to the refinement and modification of the microstructure during powder ball milling.

BAPTA-AM Nanoparticle for the Curing of Acute Kidney Injury Induced by Ischemia/Reperfusion.

Ischemia-reperfusion (I/R) is a major cause of acute kidney injury (AKI), which is associated with unacceptably high mortality rates in ICU. This research was designed to explore the therapeutic effect of BAPTA-AM (1,2-Bis(2-aminophenoxy) ethane-N,N,N,N-tetraacetic acid tetrakis(acetoxymethyl ester)) nanoparticle (BA-N) on AKI. BA-N was developed by liposome strategy and characterized by standard methods. The rat model was selected and the rats were randomly allocated into four groups: (1) Normal group; (2) Sham-operated group; (3) Model group (I/R + NS); (4) BA-N treatment group (I/R + BA-N). AKI model was established via clipping the bilateral renal artery with a microvascular clamp for 45 min. After reperfusion, serum cystatin C (Cys C), creatinine (Cr), blood urea nitrogen (BUN), lactate dehydrogenase (LDH) and caspase 3 levels were determined for the assessment of renal function. Kidney samples were then collected for the measurement of renal malondialdehyde (MDA) level and superoxide dismutase (SOD) activity. The assays of histological examination, ELISA, immunohistochemistry, western blot, TUNEL and RT-PCR were utilized for the detection of apoptosis. The results demonstrated that AKI model caused a significant decreasing in SOD activity, accompanied by a remarkable increase in Cys C, Cr, BUN, LDH, MDA, caspase 3 and cytochrome c (Cyt C) level, compared to the control group. BA-N (100 μg/kg i.v.) significantly improved renal function and histopathological appearance, restored MDA level and SOD activity, decreased Bax/Bcl-2 ratio, caspase 3 activity, Cyt C release and TUNEL positive apoptotic cells. Our studies indicated that BA-N plays a renal-protective role, probably through antiapoptotic and antioxidant mechanisms. BA-N may regulate mitochondria pathway via decreasing Bax/Bcl-2 ratio, inhibiting caspase 3 expression and Cyt C release. Overall, BA-N may have potentials as an anti-AKI drug.

The relationship between serum cystatin C level and insulin resistance in elderly patients with type 2 diabetes

Objective To study the relationship between serum cystatin C(Cys C)level and the development of insulin resistance(IR)in elderly patients with type 2 diabetes mellitus(T2DM). Methods A cross-sectional survey research involving 757 elderly patients with T2DM was performed and patients were divided into groups according to Cys C and IR levels.Serum 1evels of fasting insulin(FBI), fasting blood glucose(FPG), fasting C-peptide(FCP), glycosylated hemoglobin A1c(HbA1c), homeostasis model assessment of insulin resistance(IR)(HOMA2-IR-C), homeostasis model assessment of insulin secretion, homeostasis model assessment of insulin sensitivity(HOMA2-%S-C), micro-albuminuria(mALB)and serum lipid were measured and compared among the groups.Possible influence factors were adjusted, and the correlation between Cys C levels and IR was analyzed.The influencing factors on IR were also analyzed. Results There were statistically significant differences in ages, course of T2DM, FBI, FCP, HbA1c, urinary mALB, IR, insulin secretion, insulin sensitivity, morbidity rate of coronary heart disease, hypertension and diabetic nephropathy among the three groups(allP<0.05). Insulin sensitivity was decreased with the increase of Cys C level, while others were increased.Among 757 patients, the level of serum Cys C was positively correlated with FCP, HOMA2-IR-C levels, and was negatively correlated with HOMA2-%S-C levels(P<0.05). Multiple logistic regression analysis showed that the higher level of Cys C was independent risk factors for IR in elderly T2DM patients(OR=3.41, 95%CI: 2.22-5.22, P<0.05). Conclusions Serum Cys C level is closely related with IR in elderly T2DM, and the elevated level of serum Cys C is one of independent risk factors for elderly T2DM. Key words: Type 2 diabetes mellitus; Cysteine proteinase inhibitors; Insulin resistance

Nephrotoxicity of High and Conventional Dosing Regimens of Colistin: A Randomized Clinical Trial.

Nephrotoxicity has been a major long-standing concern about colistin.This study was designed to compare nephrotoxicity of high dose and conventional dose of colistin. A randomized open-labeled clinical trial on 40 patients with multi-drug resistant gram negative infections was designed. Patients were allocated into two equal-size groups receiving high (a loading dose of 9 million international units (MIU) and maintenance doses of 4.5 MIU every 12 h) and conventional dose (2 MIU every 8 h) of colistin. Blood samples were taken on day 1, 3, 5, 7 and 10 of treatment for measuring serum cystatin C (Cys C) levels. Incidence of acute kidney injury (AKI) was also evaluated based on RIFLE criteria. Mean ± sd of the difference between baseline and day 10 Cys C levels in high dose and conventional dose groups were 1.61 ± 0.90 and 1.32 ± 0.48, respectively (P = 0.30). Within group analysis showed increase in Cys C levels in both groups (P = 0.001),however, no significant difference in Cys C levels was seen in between groups analysis (P = 0.13). Prevalence of AKI based on RIFLE criteria was 60% and 15% in high dose and conventional dose groups, respectively (P = 0.003). Comparison of Cys C between AKI (mean ± sd) and non-AKI (mean ± sd) patients, irrespective of colistin dosage regimens, confirmed a significant difference (P < 0.0001). Although, colistin-induced nephrotoxicity, determined by Cys C levels, was not confirmed by our findings, however, higher incidence of AKI in high-dose group, defined by RIFLE criteria, along with higher levels of Cys C in AKI patients are supportive of the higher risk of renal toxicity associated with high-dose regimen of colistin. More RCTs with a larger sample size are recommended.

Diagnostic value of serum cystatin C for acute kidney injury in patients with liver cirrhosis

Objective: To determine the diagnostic value of serum cystatin C (Cys C) for acute kidney injury (AKI) in patients with liver cirrhosis. Methods: Serum Cys C levels in 150 liver cirrhosis patients (88 AKI and 62 non-AKI patients) were measured by the Particle-Enhanced Nephelometric Immuno-Assay. The accuracy of serum Cys C for the diagnosis of AKI in liver cirrhosis was evaluated by the ROC curve. Results: Liver cirrhosis patients with AKI had significantly higher serum Cys C levels [2.37 (1.75-2.83) mg/L] than those without AKI [0.97 (0.85-1.09) g/L] (P <0.001). Serum Cys C level was highest in the acute tubular necrosis group [5.41 (2.77-6.19) mg/L], followed by the hepatorenal syndrome group [2.55 (2.28-3.59) mg/L] and prerenal azotemia group [2.07 (1.70-2.41) mg/L], and the serum Cys C level was significantly different between the three groups (P <0.001). In addition, patients with AKI were further divided into infection group and non-infection group. Serum Cys C level was significantly higher in the infection group than in the non-infection group (P <0.05). The area under the ROC curve of serum Cys C for the diagnosis of AKI in liver cirrhosis was 0.99 (0.98-1.00) at a cut-off value of 1.36 mg/L, and the sensitivity and specificity were 97% and 95%, respectively. Conclusion: Serum Cys C is a good marker for detecting AKI in liver cirrhosis, and the different levels of increase in Cys C may be useful in differentiating the different types of AKI.

Requirement of standardized ileal digestible valine to lysine ratio for 8- to 14-kg pigs

The objective was to define the Val requirement for weaned piglets in the context of reducing the dietary protein content. A dose–response experiment was conducted to estimate the standardized ileal digestible (SID) Val to Lys ratio required to support the optimum growth of post-weaned piglets. In this study, 96 pigs weighing 8 kg were allotted to one of six dietary treatments (16 pigs for each dietary treatment) and were housed individually. Diets were formulated to provide 0.58, 0.62, 0.66, 0.70, 0.74 and 0.78 SID Val : Lys by adding graded levels of crystallinel-Val to the 0.58 SID Val : Lys diet. Lysine was sub-limiting and supplied 90% of the recommendation (10.95 g SID Lys/kg equal to 11.8 g/kg total Lys). Average daily feed intake (ADFI), average daily gain (ADG) and gain to feed ratio (G : F) were determined during a 14-day period ofad libitum feeding. Blood and urine samples were taken at the end of each week (day 7 and 14 of the experiment) 3 h after feeding the experimental diets. The maximum ADFI and ADG were obtained in pigs fed the 0.78 SID Val : Lys diet; it was not different from the results of pigs fed 0.70 SID Val : Lys diet. The highest G : F was obtained in pigs fed 0.70 SID Val : Lys. The plasma concentration of Val increased linearly (P<0.001) as the dietary SID Val : Lys increased. The increasing dietary Val : Lys also resulted in a linear increase in Cys (P<0.001) and a quadratic increase in Arg (P=0.003), Lys (P=0.05) and Phe (P=0.009). The plasma Gly showed a quadratic decrease (P=0.05) as the dietary Val : Lys increased. Neither plasma nor urinary urea to creatinine ratio was affected by treatment. The minimum SID Val : Lys required to maximize ADFI, ADG and G : F was estimated at 0.67 SID Val : Lys by a broken-line model, and at 0.71 SID Val : Lys by a curvilinear plateau model. The Val deficiency caused a reduction in ADFI, and Val supplementation above the requirement did not impair animal performance. In conclusion, 0.70 SID Val : Lys is suggested as the Val requirement for 8 to 14 kg individually housed pigs.

Can the difference in serum concentration of urea and cystatin C be used in diagnosis and prognosis of heart failure?

Changes in renal function are an important diagnostic and prognostic indicator in patients with heart failure (HF). They are caused by decreased renal perfusion and consequently decreased glomerular filtration rate (GFR), or by the effect of increased neurohormonal activity (sympathetic nervous system [SNS], rennin–angiotensin–aldosterone system [RAAS] and arginine vasopressin [AVP]). However, the increase of serum concentration of urea, creatinine and other metabolites is not specific for HF. Therefore, it is not possible to distinguish HF from renal diseases solely based on the increase of their concentration, since the increase of their concentration caused by the decrease of GFR cannot be differentiated from the increase due to neurohormonal activity. Urea and cystatin C (Cys C) have different mechanisms of renal elimination, so it can be assumed that in HF their concentrations will not be increased proportionally, what can be used for diagnostic and prognostic purposes. After glomerular filtration Cy C undergoes proximal tubular reabsorption and breakdown, without returning to the blood flow. Since it is not secreted, its serum concentration depends only on GFR. In contrast to Cys C, urea is filtered in glomerulus and subsequently reabsorbed in proximal tubules and colleting duct. Reabsorption of urea is modified by effects of SNS, RAAS and AVP. Therefore its serum concentration depends upon GFR and neurohormonal effect on the tubular function. Since the increase of serum concentration of Cys C is caused only by the effect of the decreased renal perfusion on GFR, while the increase of urea is a result from both decreased GFR and tubular effects of increased neurohormonal activity, the paper hypothesis is that in HF the increase of urea will be significantly higher than the increase of serum Cys C, while in the patients with renal diseases their increase would be mostly proportional. It can be assumed that the disproportion between the increase of Cys C and urea would indicate an increased neurohormonal activity in patients with HF and correlate with its activity. If this hypothesis is proved correct, this parameter could be used in HF diagnosis and risk stratification of such patients.

Ozone affects ascorbate and glutathione biosynthesis as well as amino acid contents in three Euramerican poplar genotypes

Ozone is an air pollutant that causes oxidative stress by generation of reactive oxygen species (ROS) within the leaf. The capacity to detoxify ROS and repair ROS-induced damage may contribute to ozone tolerance. Ascorbate and glutathione are known to be key players in detoxification. Ozone effects on their biosynthesis and on amino acid metabolism were investigated in three Euramerican poplar genotypes (Populus deltoides Bartr. × Populus nigra L.) differing in ozone sensitivity. Total ascorbate and glutathione contents were increased in response to ozone in all genotypes, with the most resistant genotype (Carpaccio) showing an increase of up to 70%. Reduced ascorbate (ASA) concentration at least doubled in the two most resistant genotypes (Carpaccio and Cima), whereas the most sensitive genotype (Robusta) seemed unable to regenerate ASA from oxidized ascorbate (DHA), leading to an increase of 80% of the oxidized form. Increased ascorbate (ASA + DHA) content correlated with the increase in gene expression in its biosynthetic pathway, especially the putative gene of GDP-l-galactose phosphorylase VTC2. Increased cysteine availability combined with increased expression of γ-glutamylcysteine synthetase (GSH1) and glutathione synthetase (GSH2) genes allows higher glutathione biosynthesis in response to ozone, particularly in Carpaccio. In addition, ozone caused a remobilization of amino acids with a decreased pool of total amino acids and an increase of Cys and putrescine, especially in Carpaccio. In addition, the expression of genes encoding threonine aldolase was strongly induced only in the most tolerant genotype, Carpaccio. Reduced ascorbate levels could partly explain the sensitivity to ozone for Robusta but not for Cima. Reduced ascorbate level alone is not sufficient to account for ozone tolerance in poplar, and it is necessary to consider several other factors including glutathione content.

Changes in cysteine and O-acetyl- l-serine levels in the microalga Chlorella sorokiniana in response to the S-nutritional status

We analyzed the effects of deprivation and subsequent restoration of sulphate (S) in the nutrient solution on cysteine (Cys) and O-acetyl- l-serine (OAS) levels in Chlorella sorokiniana (211/8k). The removal of S from the culture medium caused a time-dependent increase in O-acetyl- l-serine(thiol)lyase (OASTL) activity and a decrease in soluble proteins content. The protein gel blot analysis was used to show that OASTL isoforms are located in the chloroplast and in the cytoplasm of S-starved cells. S-deprivation caused a decrease in the intracellular levels of Cys and glutathione (GSH) and an increase in serine (Ser) and OAS, reflecting an imbalance between sulphur and nitrogen assimilation. Re-supplying of sulphate to S-starved cells produced a decrease in OAS levels and concomitant rapid increase in Cys and GSH concentrations. The simultaneous addition of OAS and sulphate to S-starved cells did not further increase the concentration of Cys, suggesting the existence of a threshold level of intracellular Cys that is independent of the cellular concentration of OAS. Our findings that OAS is stored during S-starvation and that its quick decrease appears to be coupled with the increase of Cys levels upon re-supply of sulphate, imply that the central role that these two compounds play is in the regulation of sulphur-assimilating enzymes in response to the S status of the cell.

Protection of growth and photosynthesis of Brassica juncea genotype with dual type sulfur transport system against sulfur deprivation by coordinate changes in the activities of sulfur metabolism enzymes and cysteine and glutathione production

Mustard (Brassica juncea L. Czern and Coss.) cvs. Pusa Jai Kisan (with low-affinity S transporter (LAT) system) and Pusa Bold (with dual, low- and high-affinity transporters (LAT + HAT) system) were supplied with 0 or 1 mM S in hydroponics culture, and the coordinate changes in growth traits (plant dry weight and leaf area), photosynthetic traits (photosynthetic rate, intercellular CO2, F v/F m, and chlorophyll content), activities of key enzymes of sulfur metabolism, such as ATP-sulfurylase (ATP-S), serine acetyltransferase (SAT), and glutathione reductase (GR), and the contents of cysteine (Cys) and glutathione (GSH) were studied in 30 days after sowing. The results showed that cv. Pusa Jai Kisan was more sensitive to S deprivation than cv. Pusa Bold. In cv. Pusa Jai Kisan, S deprivation resulted in a stronger decrease of plant growth and photosynthetic traits, Cys and GSH contents, and a notable decline in activity of ATP-S. S deprivation up-regulated GR activity to a greater extent in cv. Pusa Bold. In contrast, despite the activity of SAT, an enzyme involved in the final step of Cys biosynthesis, was increased in cv. Pusa Jai Kisan stronger than in cv. Pusa Bold under S-deprivation, it could not be translated into the increase in Cys and, thus, GSH contents and a consequent improvement in growth and photosynthesis. The study demonstrated that cv. Pusa Bold (with LAT + HAT) can be a promising cultivar for activation of Cys and/or GSH biosyntheses and increased plant tolerance to S-deprivation conditions.

Effects of glycine supplementation at varying levels of methionine and cystine on the growth performance of broilers fed reduced crude protein diets

Two experiments were conducted to investigate Gly addition to reduced crude protein corn–soybean meal (C-SBM) diets with varying levels of TSAA achieved by varying Met and Cys. The experiments were conducted with female Ross 708 broilers in brooder batteries from 0 to 18 d posthatching. Treatments had 6 replicates with 6 broilers/pen. Diets in all experiments were fed without or with Gly supplementation to contain 2.32% total Gly + Ser. All diets were C-SBM based and formulated to contained 1.27% standardized ileal digestible Lys supplemented with 0.20% Lys (0.394% Lys·SO4) and to meet or exceed the requirement of all nutrients except Met and Cys where appropriate. Experiment 1 consisted of 8 dietary treatments. Three ratios of Met to Cys (60:40, 50:50, and 40:60) were used on a mole for mole basis to achieve 0.063 mol of TSAA/kg of feed and a positive control with Met:Cys of 50:50 at 0.76 TSAA:Lys. Glycine supplementation did not affect ADG or ADFI; however, G:F was increased (P = 0.003) with Gly supplementation. An increase in Cys and a decrease in Met resulted in a decrease (P = 0.028) in ADG but had no effect on ADFI or G:F. In experiment 2, Met was kept constant at a marginal level of 0.45% and Cys was increased in 0.05% increments from 0.35 to 0.50%. Glycine supplementation had no main effect on ADG, ADFI, or G:F; however, Gly increased G:F at the lower levels of Cys but not at the higher levels (Gly × Cys, P = 0.031). A linear decrease (P = 0.071) was found in ADFI with increasing Cys supplementation. These data indicate that Gly increased G:F in female broilers fed suboptimal levels of Met and Cys but not at Cys levels at or above the requirement. This implies that the synthesis of Cys accounts for a portion of the increased G:F observed from Gly supplementation in female broilers fed reduced CP C-SBM diets.

Value of serum cystatin C for early diagnosis of renal damage in patients with liver cirrhosis

Objective To investigate the diagnostic value of serum Cystatin C for early detection of renal damage in patients with liver cirrhosis. Methods 24-h creatinine clearance (CCr), serum level of cystatin C (CysC) and serum creatinine were measured in 76 patients with cirrhosis and t-test,Pearson's correlation test and ROC curve were used to evaluate the diagnostic significance of Cys C.Results The increase in Cys C level was associated with a decrease of CCr in the patients. Both Cys C and SCr were inversely correlated with CCr ( CysC: r =- 0. 763, P ＜ 0. 001; SCr: r=-0. 571,P＜0.01). Meanwhile, the area under the ROC curve was significantly higher in Cys C than in SCr (0. 830 vs. 0. 612). Conclusion Cystatin C is a more accurate and sensitive marker of renal diagnosis in liver cirrhosis. Detection of Cys C level in cirrhotic patients is of great significance for the prevention of liver-kidney syndrome. Key words: Liver cirrhosis; Renal damage; Cystatin C

Time course of low molecular weight proteins in the early kidney transplantation period--influence of corticosteroids

Cystatin C (Cys C) is an established new marker of renal function in patients with various renal diseases and in kidney transplantation. However, few data are available for the early post-transplantation period. Twenty-two patients who underwent renal transplantation (RTx) were evaluated for the kinetics of Cys C from day 0 to 14 in relation to creatinine and beta-2 microglobulin (B2MG). Blood samples were obtained immediately before and after transplantation and on a daily basis thereafter. Serum levels before transplantation (100%) were used to calculate reduction ratios. The decrease of the analytes differed considerably: immediately after RTx Cys C declined by 27.3% (P < 0.01). However, after 3 days, on average, all patients showed a significant increase in Cys C levels (15+/-2.5%; P < 0.01). B2MG levels fell quickly by 55.4 and 73.8% after days 1 and 7, respectively, and remained stable thereafter. In contrast, creatinine did not decrease immediately after RTx but fell slowly by 67.5% at the end of the study. Prior to rejection, all analytes showed a similar behaviour. Rejection treatment with high-dose methylprednisolone induced a significant increase in Cys C (+22.8+/-7.9%, P < 0.05), while in parallel, creatinine and B2MG decreased (-12.9+/-3.4 and -8.4+/-6.89%). Corticosteroid treatment for induction of immunosuppression or rejection therapy significantly induces Cys C, but decreases B2MG. Cys C and B2MG are not helpful in establishing the diagnosis of rejection earlier. Thus, our data indicate that Cys C and B2MG testing does not accurately reflect changes in the glomerular filtration rate early after transplantation.

A Decrease in Cysteine Levels Causes the Glutathione Deficiency of Aging in the Mosquito

Our previous results indicated that a glutathione (GSH) deficiency is a determinant of the aging process in many tissues and organisms. Correction of this deficiency in the aging mosquito by feeding the cysteine (Cys) precursor magnesium thiazolidine carboxylic acid (MgTc) suggested that the cause could be a lack of Cys. Adult mosquitoes (Aedes aegypti) were fed either a control diet or a diet supplemented with MgTC and then were analyzed for their Cys, cystine, GSH, and glutathione disulfide contents with our HPLC method. The life span profile of Cys levels paralleled that of GSH in the control group with high levels in the young that decreased during maturity and aging. Cystine and glutathione disulfide were undetectable. The causal relationship between the Cys and the GSH deficiencies was shown in the MgTC-supplemented group with an 83% increase in Cys and a 39% increase in GSH relative to control values. Further the conversion steps of MgTC to Cys and then to GSH were verified by use of buthionine sulfoximine. These results demonstrate that a Cys deficiency occurs in the aging mosquito and is the cause of the GSH deficiency.