Immunization with recombinant protein Ag43::UpaH with alum and 1,25(OH)2D3 adjuvants significantly protects Balb/C mice against urinary tract infection caused by uropathogenic Escherichia coli.

The majority of urinary tract infections (UTIs) are caused by uropathogenic Escherichia coli (UPEC). Designing a vaccine will certainly reduce the occurrence of infection and antibiotic resistance of the isolates. Antigen 43 (Ag43) and autotransporter H (UpaH) have been associated with the virulence of UPEC. In the present study, the efficacy of different formulations of a hybrid protein composed of Ag43 and UpaH with and without alum and 1,25(OH)2D3 (Vitamin D3) adjuvants were evaluated in mice model. A significant increase in IgG and cellular responses was developed against Ag43::UpaH as compared to the control mice. The addition of alum or a mixture of alum and Vitamin D3 to the protein significantly enhanced the serum IgG responses and tended to remain in a steady state until 6 months. In addition, the mentioned formulations produced significant amounts of IgG1, IL-4, and IL-17 as compared to the fusion protein alone. In addition to the mentioned formulations, the combination of protein with Vitamin D3 also resulted in significantly higher serum IgA and IFN-γ levels as compared to the fusion protein alone. Mice immunized with fusion plus alum and formulation protein admixed with both alum and Vitamin D3 significantly reduced the bacterial load in the bladders and kidneys of mice as compared to the control. In this study, for the first time, the ability of a novel hybrid protein in combination with adjuvants alum and Vitamin D3 was evaluated against UPEC. Our results indicated that fusion Ag43::UpaH admixed with alum and Vitamin D3 could be a promising candidate against UTIs.

[Preventive effect of integrative medical therapy on children Henoch-Schonleln purpura with renal impairment].

OBJECTIVE: To observe the clinical effect of integrative medicinal therapy in treating children Henoch-Schonlein purpura (HSP) and its preventive effect on complicated renal impairment. METHODS: One hundred and twenty children with HSP were equally randomized into two groups, the treated group and the control group. Both were treated with conventional Western medical therapy, but Sanhuang Qingxue Yin (SQY, a Chinese herbal drug) was given additionally to the treated group. Besides, a group consisted of 30 healthy children was set up as a normal control. Changes of symptoms, physical signs, routine urine, plasma endothelin-1 (ET-1) and urinary levels of beta2-microglobulin (beta2-MG), albumin (ALB) and immunoglobulin G (IgG) before and after treatment were observed, and the recurrence was monitored. RESULTS: The cure rate and the total effective rate in the treated group were 80.0% and 98.3%, while those in the control group were 61.7% and 88.3%, showing significant differences between groups (P < 0.05); the disappearance time of clinical symptoms was shorter in the treated group than in the control group, also showing a significant difference (P < 0.01); after 1-month treatment, levels of plasma ET-1, and urinary beta2-MG, ALB and IgG were improved in the treated group, reaching the levels opproximate to those in the normal control (P > 0.05), significant difference was shown as compared with those in the control group and with those before treatment respectively (P < 0.01, P < 0.05). The recurrent rate was 13.33% in the treated group and 30.0% in the control group, and they were statistically different (P < 0.05). CONCLUSION: The integrative medicinal therapy is good for treating HSP in children, it could not only obviously relieve clinical symptoms, shorten the illness course and reduce the recurrent rate, but also effectively prevent the occurrence of renal impairment.

Clinical observation on chemical damage of nephron and the preventive and therapeutic effects of Baoshen Mixture on it.

OBJECTIVE: To observe the change of nephron damaged by chemotherapy and to evaluate the effect of Baoshen Mixture (, BSM) in protecting and treating damaged nephrons. METHODS: Four hundred tumor patients with normal renal function and ready to receive chemotherapy were randomly assigned to two groups. Both groups received one cycle of chemotherapy program of 28-30 days with conventional hydratization, alkalization and chloridization. To the 200 cases in the treated group BSM was given orally thrice a day, 150 mL every time for 15 successive days and the other 200 cases in the control group were treated by chemotherapy alone. The clinical efficacy was compared after treatment, and the changed condition of damaged nephrons were monitored dynamically and compared at different time points (the 3rd, 7th, 14th and 21st day after chemotherapy) by measuring the micro-globulin beta(2) (beta(2)-MG), albumin (Alb) and immunoglobulin G (IgG) levels in urine with radioimmunoassay (RIA). RESULTS: (1) The effective rates in the treated group at the 4 time points of observation were all higher than those in the control group respectively (P<0.05 or P<0.01); (2) Less occurrence of abnormal beta(2)-M, Alb and IgG levels on the 14th and 21st day in the treated group took place compared to that in the control group (P<0.01); (3) Urinary levels of beta(2)-MG, Alb and IgG reached the peak on the 7th day in both groups, and then, they came down gradually and returned to the normal level on the 21st day. However, comparison between the two groups showed that all the three parameters in the treated group on day 3, 14 and 21 were lower than the respective one at the corresponding time points in the control group (P<0.05 or P<0.01). CONCLUSION: The chemotherapy damage on nephron is regular in time, and reversible when treated suitably. TCM shows a marked effect in protecting and treating the damage on nephron caused by chemotherapy.

Urine biochemical markers of early renal dysfunction are associated with iron overload in beta-thalassaemia.

Renal dysfunction in thalassemia patients can be attributed to chronic anemia, and iron overload as well as to desferioxamine (DFO) toxicity. We analyzed the urine of 91 well-maintained homozygous beta-thalassemia patients, with no evidence of renal disease, for early evidence of kidney dysfunction by means of electrophoresis and quantitative biochemical tests. Measurement of liver magnetic resonance imaging (MRI) T2 values and serum ferritin concentration was used to estimate iron overload. In 55 of the 91 patients, urine analysis indicated signs of tubular dysfunction. The urine concentration of albumin and beta 2-microglobulin, as well as the activity of N-acetyl-beta-D-glucosaminidase (NAG), correlated positively with serum ferritin concentration and liver iron deposition, as detected by MRI T2 values. This suggested that the cause of renal dysfunction in homozygous beta-thalassemia is iron overload. On the other hand, the same urine markers did not correlate with age, indicating that chronic anemia or desferrioxamine (DFO) treatment are not related to renal dysfunction in thalassemia.

Nephrotoxicity of ifosfamide, carboplatin and etoposide (ICE) alone or combined with extracorporeal or radiant-heat-induced whole-body hyperthermia.

Although whole-body hyperthermia combined with specific genotoxic chemotherapy can be shown to enhance neoplastic cell killing without a concomitant rise in bone marrow toxicity, nephrotoxicity can become treatment-limiting. This study compares the kidney toxicity to the kidney of ifosfamide, carboplatin and etoposide (ICE) chemotherapy alone, and ICE chemotherapy combined with either extracorporeal (e-WBH) or radiant-heat-induced hyperthermia (r-WBH) in 43 patients with refractory sarcoma. Within 3 days of ICE chemotherapy treatment there was a significant increase in urinary protein excretion and a reduction of the glomerular filtration rate. These effects were more pronounced if WBH was added. The use of immunoluminometric assays revealed a predominance of low-molecular-mass proteins. This increase in protein excretion persisted in the e-WBH-treated group, whereas it vanished within 3 weeks in both the group treated with ICE alone and that treated with r-WBH. Our findings suggest that ICE chemotherapy causes transient tubular and glomerular damage, which is enhanced by WBH. In terms of long-term nephrotoxicity e-WBH was more nephrotoxic than r-WBH. This finding is consistent with our clinical observations.

[Relationship between Syndrome-Type in TCM and four trace urinary proteins in patients with bronchial asthma].

OBJECTIVE: To explore the possible relationship between Syndrome-Type in TCM and the 4 trace urinary proteins in patients with bronchial asthma. METHODS: The 4 kinds of trace urinary proteins in 217 patients with asthma were measured by radioimmunoassay, and that in 66 normal subjects were compared. RESULTS: The results showed that there were increments of urinary albumin, urinary IgG, urinary beta 2-microglobulin and urinary Tamm-Horsfall protein in patients with asthma; and the gradual increase tended to be accompanied by the continuous aggravation of patient's condition on TCM Syndrome-Type. Furthermore, these datas proved that the 4 trace urinary proteins might be the most sensitive indicators for detecting impaired renal functions than serum blood urea nitrogen and creatinine. CONCLUSIONS: There were the objective material foundations on TCM Syndrome-Type in asthmatics, which consisted of renal glomerular dysfunctions to filter out albumin and IgG, renal tubular dysfunction to reabsorb beta 2-microglobulin, and to synthesize and excrete Tamm-Horsfall protein.

Fish oil in diabetic nephropathy.

OBJECTIVE: Recent studies in nondiabetic kidney diseases suggest that dietary supplementation with n-3 polyunsaturated fatty acids (fish oil) may have beneficial effects on albuminuria, kidney function, arterial blood pressure, and dyslipidemia. Therefore, we evaluated the long-term effect of fish oil in diabetic nephropathy. RESEARCH DESIGN AND METHODS: A 1-year double-blind randomized controlled study comparing fish oil (4.6 g n-3 fatty acids/day) with placebo (olive oil) was performed in an outpatient clinic in a tertiary referral center. Thirty-six normotensive IDDM patients with diabetic nephropathy were included; 18 were treated with fish oil. Seven patients dropped out (four received fish oil), and results for the remaining 29 are presented. Albuminuria (enzyme immunoassay), glomerular filtration rate (51Cr-labeled EDTA plasma clearance), 24-h ambulatory blood pressure, and lipid profile were determined every 6 months. RESULTS: Albuminuria increased by 22% (1-46%) (mean [95% CI]) in the fish oil group vs. 15% (-11-49%) in the placebo group (NS). Glomerular filtration rate decreased from 116 +/- 7 to 105 +/- 7 ml.min-1.1.73 m-2 (mean +/- SE) vs. from 108 +/- 6 to 103 +/- 7, fish oil and placebo, respectively (NS). No significant changes occurred in 24-h ambulatory blood pressure: from 141 +/- 4/82 +/- 2 mmHg to 142 +/- 5/83 +/- 2 vs. from 140 +/- 4/78 +/- 2 to 144 +/- 4/80 +/- 3, fish oil and placebo, respectively (NS). In the fish oil group, serum triglycerides (median [range]) decreased from 0.97 (0.5-4.0) mmol/l to 0.8 (0.4-3.0) vs. from 1.01 (0.4-2.0) to 1.09 (0.4-2.0) in the placebo group (P < 0.05) and VLDL cholesterol decreased from 0.45 (0.23-1.88) to 0.37 (0.21-1.43) mmol/l vs. from 0.44 (0.21-0.94) to 0.41 (0.17-1.94) (P < 0.05), but total and LDL cholesterol rose in the fish oil compared with the placebo group. CONCLUSIONS: Our study does not suggest that fish oil has beneficial effects on albuminuria, kidney function, blood pressure, and dyslipidemia in normotensive IDDM patients suffering from diabetic nephropathy.

Colostrum protein digestion in newborn lambs.

The efficiency of colostral protein digestion was studied in nine newborn lambs fed one meal of bovine colostrum 3 h after birth. The results were compared with those obtained in two unfed lambs and four lambs fed bovine milk. The protein and peptide composition [immunoglobulins G1 and (IgG1), beta-lactoglobulin, alpha-lactalbumin, caseins and peptides resulting from casein hydrolysis] of digesta, gastrointestinal tissues, blood and urine were determined in samples taken 0.75 or 4 h after feeding. The amounts of ingested proteins in lambs fed colostrum were much higher than in those fed the milk diet, and their abomasal emptying was faster. alpha-Lactalbumin was highly degraded by abomasal and intestinal proteases, whereas beta-lactoglobulin and in particular the immunoglobulins were less sensitive. The gastric emptying of caseins was delayed in and the kinetics of appearance of peptides originating from casein hydrolysis was comparable to that observed in lambs fed milk and in 1-mo-old preruminant calves. Thirty-five percent of dietary amino acids ingested as colostrum were available within 4 h for amino acid metabolism; this percentage was 54% in the milk-fed lambs. In the lambs fed colostrum, these amino acids were provided by beta-lactoglobulin, casein and IgG1 (0.52, 0.43 and 0.30 g/kg body wt, respectively), whereas in milk-fed animals casein and beta-lactoglobulin were the most important sources of these amino acids (0.40 and 0.20 g/kg, respectively).

Chronic effects of omega-3 fatty acids (fish oil) in a rat 5/6 renal ablation model.

It has been proposed that fish oil dietary supplementation in the chronic rat 5/6 renal ablation model may be either protective or toxic. These conflicting hypotheses were tested in rats who underwent renal ablation or sham surgery. Twenty rats received sham surgery, and 40 received 5/6 renal ablation. All rats were fed a regular laboratory diet up to 1 week postsurgery. At that time, one half of the renal ablation group was provided with an isocaloric diet supplemented with 24% MaxEPA (fish oil), 1% safflower oil, and antioxidants. The renal ablation rats developed hypertension, albuminuria, gammaglobulinuria, and a decline in glomerular filtration rate, which was less in the fish oil group compared with that in the regular laboratory diet group at 10 and 20 wk postsurgery. The fish oil renal ablation rats had significantly less glomerulosclerosis than did the regular laboratory diet renal ablation animals, and no more glomerular fibrin deposition than did the sham controls. The renal ablation regular laboratory diet rats had a significant dyslipidemia at 20 wk which was prevented in the fish oil renal ablation cohort. The fish oil renal ablation rats also demonstrated a significant decline in renal tissue arachidonic acid incorporation and a concomitant increase in eicosapentaenoic acid and docosahexaenoic acid incorporation. The mortality of the renal ablation group was greater than that of the sham controls but not significantly different for the fish oil or the regular laboratory diet groups. These results support the hypothesis that the fish oil diet containing specific antioxidant, vitamin E, and essential fatty acid supplementation is protective in the rat remnant nephron model and prevents the evolution of glomerulosclerosis with associated renal functional impairment, while preserving glomerular filtration.

Comparative efficacy of dietary treatments on renal function in rats with sub-total nephrectomy: renal polyunsaturated fatty acid incorporation and prostaglandin excretion.

The efficacy of dietary intervention with either 6% protein restriction, fish oil or safflower oil was assessed in the remnant nephron model. Female Munich Wistar rats were prefed for one week prior to 5/6 nephrectomy and followed for the ensuing 28 days. Fish oil, safflower oil and protein restriction prevented the gammaglobulinuria but only fish oil lessened the albuminuria in this model. The remnant nephrons of the fish oil treated rats contained less arachidonic acid and greater quantities of eicosapentaenoic and docosahexaenoic acid than the safflower oil or lab chow fed control rats. The fish oil, and to a lesser extent the safflower oil, treated animals had a higher ratio of 6 keto PGF1 alpha to TX B2 metabolites in their urine. We suggest these changes may be responsible for the lessening in urine protein excretion. Fish oil feeding was more effective than severe protein restriction or safflower oil dietary supplementation in lessening both the gammaglobulinuria and albuminuria of the remnant nephron model.

Production and turnover of IgG1 and IgG2 immunoglobulins in the bovine around parturition.

Production rates (entry rate into blood plasma) and other metabolic parameters for the IgG1 and IgG2 subclasses of immunoglobulins in mammary secretions (ratio of about 7 to 1) were determined in cows around the time of parturition by both single-injection and continuous-infusion isotope-dilution techniques. Four cows were given a single dose of 150 to 200 muCi of iodine-125 labeled IgG1 and 100 to 250 muCi of iodine-131 labeled IgG2 at 2 to 1 wk before parturition. Four cows, including two of the above, were infused continuously with constant amounts of the labeled immunoglobulins starting at 11 to 4 days before parturition. All cows were maintained until 4 to 6 days after parturition for monitoring the specific activities of iodine-125 labeled IgG1 and iodine-131 labeled IgG2 in the plasma and mammary secretions. Maximum entry rates of IgG1 and IgG2 were between 3 and 1 day prepartum with means of 125 and 60 g/500 kg body weight per day. The exchangeable pool means for IgG1 and IgG2 were 619 and 643 g/500 kg body weight, and both immunoglobulins were divided almost equally between the intra- and extravascular pools. A greatly increased production and a shortened half-life or greater turnover for plasma IgG1 occurs around the time of parturition which can account for the large accumulation of IgG1 in colostrum.