Serum Folate and Vitamine B12 Levels in Acute and Chronic Renal Disease. Effect of Peritoneal Dialysis

Serum folate and vitamin B₁₂ levels have been measured in 32 patients with renal failure. The initial mean serum folate level was raised above normal in seven patients with acute renal failure whereas the mean level in eight patients severely ill from chronic renal failure was significantly lower than normal. Serum folate levels fell during peritoneal dialysis and rose between dialyses in all these patients and also in one patient who was dialysed for acute pancreatitis.The mean serum B₁₂ level was raised in patients with both acute and chronic renal failure, but there was no consistent change in serum B₁₂ level during dialysis.Hypersegmented polymorphs were present in the peripheral blood film of most of the patients with acute or chronic renal failure. Their presence bore no relation to the clinical state, blood urea, serum folate, or serum B₁₂ level of the patients.     

Serum Levels of Carcinoembryonic Antigen in Patients with Type 2 Diabetes

Objective: To investigate whether serum carcinoembryonic antigen (CEA) levels are associated with type 2 diabetes mellitus (T2DM) and glycated hemoglobin (HbA1c).Methods: A comparative, cross-sectional, observational study was conducted at Jordan University Hospital, Amman, Jordan, on 282 adult subjects from March 2012 to June 2015. Subjects were classified into 2 groups: T2DM subjects (n = 168) and a healthy comparison group (n = 114). Subjects with any condition known to be associated with elevated CEA levels were excluded. HbA1c and serum CEA levels were measured, and body mass index (BMI) was determined.Results: Subjects with T2DM had significantly higher mean serum CEA than controls (2.4 ± 1.5 vs. 1.5 ± 1.2 ng/mL, P<.0001). Sex did not correlate with CEA levels, while age (Spearman's rho [ρ] = 0.18, P =.002) and HbA1c (ρ = 0.56, P<.0001) did; however, age no longer correlated after correcting for diabetic status. HbA1c was the only variable shown to correlate with CEA in a stepwise linear regression (r = 0.37, P<.001).Conclusion: We observed a statistically significant association between elevated CEA and T2DM, despite average CEA values for both groups being within the reference range. In addition, serum CEA levels correlated positively with HbA1c values.Abbreviations:ADA = American Diabetes AssociationBMI = body mass indexCA 19-9 = carbohydrate antigen 19-9CEA = carcinoembryonic antigenCRP = C-reactive proteinDM = diabetes mellitusHbA1c = glycated hemoglobinJUH = Jordan University HospitalT2DM = type 2 diabetes mellitusρ = Spearman's correlation coefficient     

Increased Urine and Serum Nerve Growth Factor Levels in Interstitial Cystitis Suggest Chronic Inflammation Is Involved in the Pathogenesis of Disease

Objective

Interstitial cystitis/bladder pain syndrome (IC/BPS) is considered a bladder disorder due to localized chronic inflammation. This study investigated the nerve growth factor (NGF) levels in serum and urine in patients with IC/BPS.

Materials and Methods

Thirty patients with IC/BPS and 28 normal subjects without lower urinary tract symptoms were recruited from an outpatient clinic. IC/BPS was diagnosed by frequency, bladder pain, and the presence of glomerulations during cystoscopic hydrodistention. Serum and urine were collected before any treatment was given. Serum NGF and urinary NGF/Cr levels were compared between IC/BPS and the controls.

Results

Urinary NGF levels were significantly higher in patients with IC/PBS (26.3±11.2 pg/ml) than in controls (1.40±0.63 pg) (p = 0.014). After normalization, the urinary NGF/Cr levels were significantly greater in IC/BPS (0.69±0.38 pg/mg) than controls (0.20±0.01, p = 0.011). Relative to the levels in control subjects (1.90±0.38 pg/mL), the mean serum NGF levels were higher in patients IC/BPS patients (3.48±0.55 pg/mL) (p = 0.015). No significant correlation was found between the serum and urinary NGF levels in IC/BPS patients. However, the clinical characteristics and medical co-morbidities did not show significant difference between IC/BPS patients with a higher and lower serum NGF level.

Conclusions

Increased urinary NGF levels in IC/BPS patients suggest that chronic inflammation is involved in this bladder disorder. Increased circulating serum NGF levels were noted in over half of patients with IC/BPS, however, the urinary and serum NGF were not inter-correlated and elevated serum NGF did not relate with clinical features.     

Elevated Urine Heparanase Levels Are Associated with Proteinuria and Decreased Renal Allograft Function

Heparanase is an endo-β-glucuronidase that cleaves heparan sulfate side chains, leading to structural modifications that loosen the extracellular matrix barrier and associated with tumor metastasis, inflammation and angiogenesis. In addition, the highly sulfated heparan sulfate proteoglycans are important constituents of the glomerular basement membrane and its permselective properties. Recent studies suggest a role for heparanase in several experimental and human glomerular diseases associated with proteinuria such as diabetes, minimal change disease, and membranous nephropathy. Here, we quantified blood and urine heparanase levels in renal transplant recipients and patients with chronic kidney disease (CKD), and assessed whether alterations in heparanase levels correlate with proteinuria and renal function. We report that in transplanted patients, urinary heparanase was markedly elevated, inversely associated with estimated glomerular filtration rate (eGFR), suggesting a relationship between heparanase and graft function. In CKD patients, urinary heparanase was markedly elevated and associated with proteinuria, but not with eGFR. In addition, urinary heparanase correlated significantly with plasma heparanase in transplanted patients. Such a systemic spread of heparanase may lead to damage of cells and tissues alongside the kidney.The newly described association between heparanase, proteinuria and decreased renal function is expected to pave the way for new therapeutic options aimed at attenuating chronic renal allograft nephropathy, leading to improved graft survival and patient outcome.     

Evaluation of Serum Cyclooxygenase,Hepcidin Levels in Acute Renal Injury (AKI) Patients Following Cardiac Catheterization

Background:Acute kidney damage is a severe condition common in patients who have undergone heart surgery (catheterization) and secondary injury is also referred to as being synonymous with surgery. The goal of this research is to determine the rate of cyclooxygenase and hepcidin levels in patients with acute renal injury (AKI) following cardiac catheterization.Methods:The study is performed on (81) patients (64 males and 17 females) aged 40-75 years. Data from most patients are reported in the form of age, gender, and smoking background questionnaire.Results:The results indicate a significant increase in serum levels of cyclooxygenase and hepcidin levels in patients with severe renal insufficiency after cardiac catheterization by (79%) males versus (21%) females.Conclusion:In this study, improved risk prediction could enhance patient monitoring and treatment after surgery, direct patient treatment and decision making, and enhance participation in AKI interventional trials.Key Words: AKI, Cardiac surgery, Chronic kidney disease, Cyclooxygenase, Hepcidin     

The F11 Receptor (F11R)/Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A) in cancer progression

Molecular and Cellular Biochemistry - The F11 Receptor (F11R), also called Junctional Adhesion Molecule-A (JAM-A) (F11R/JAM-A), is a transmembrane glycoprotein of the immunoglobulin superfamily,...     

The Role of Serum Magnesium and Calcium on the Association between Adiponectin Levels and All-Cause Mortality in End-Stage Renal Disease Patients

Background

Adiponectin (ADPN) is the most abundant adipocyte-specific cytokine that plays an important role in energy homeostasis by regulating lipid and glucose metabolism. Studies of the impact of ADPN on clinical outcomes have yielded contradictory results so far. Here, we examined the association of ADPN with serum magnesium (s-Mg) and calcium (s-Ca) levels and explored the possibility whether these two factors could modify the relationship between ADPN and all-cause mortality in patients with end-stage renal disease.

Methodology/Principal Findings

After baseline assessment, 47 hemodialysis and 27 peritoneal dialysis patients were followed- up for a median period of 50 months. S-Mg and s-Ca levels emerged as positive and negative predictors of ADPN levels, respectively. During the follow-up period 18 deaths occurred. There was a significant 4% increased risk for all-cause mortality for each 1-µg/ml increment of ADPN (crude HR, 1.04; 95% CI, 1.01–1.07), even after adjustment for s-Mg and s-Ca levels, dialysis mode, age, albumin and C-reactive protein. Cox analysis stratified by s-Mg levels (below and above the median value of 2.45 mg/dl) and s-Ca levels (below and above the median value of 9.3 mg/dl), revealed ADPN as an independent predictor of total mortality only in the low s-Mg and high s-Ca groups. Furthermore, low s-Mg and high s-Ca levels were independently associated with malnutrition, inflammation, arterial stiffening and risk of death.

Conclusions/Significance

The predictive value of ADPN in all-cause mortality in end-stage renal disease patients appears to be critically dependent on s-Mg and s-Ca levels. Conversely, s-Mg and s-Ca may impact on clinical outcomes by directly modifying the ADPN’s bioactivity.     

Interstitial Lung Disease in Coppersmiths in High Serum Copper Levels

Coppersmith is a worker who uses copper most commonly for the production of kitchen appliances in Turkey. This is an ancient occupation practiced for centuries in Turkey. Our objective was to investigate the prevalence of parenchymal lung diseases among coppersmiths in Kahramanmaras city in Turkey. Thirty coppersmiths were included to the study, and they all signed an informed consent. Demographics, spirometric test results and high-resolution computed tomography (HRCT) scans, and blood samples were obtained. Laboratory analysis of the serum samples showed that serum copper levels of the subjects were 0.93 ± 0.14 mg/L. Serum copper level in control group was found as 0.70 ± 0.14 mg/L, and it was significantly different between the two groups (p < 0.05). Of 30 coppersmiths, 17 HRCT findings are abnormal and seen with diffuse parenchymal interstitial lung disease pattern—ten (58.8%) respiratory bronchiolitis interstitial lung disease, five (29.4%) nonspecific interstitial pneumonia, and two (11.8%) usual interstitial pneumonia. The most prevalent HRCT pattern was micronodular pattern in workers. This is the first field study reporting the radiologic findings of coppersmiths and effect of the occupation on lung diseases.     

Serum Renalase Levels Correlate with Disease Activity in Lupus Nephritis

Introduction

Lupus nephritis (LN) is among the most serious complications of systemic lupus erythematosus (SLE), which causes significant morbidity and mortality. Renalase is a novel, kidney-secreted cytokine-like protein that promotes cell survival. Here, we aimed to investigate the relationship of serum renalase levels with LN and its role in the disease progression of LN.

Methods

For this cross-sectional study, 67 LN patients and 35 healthy controls were enrolled. Seventeen active LN patients who received standard therapies were followed up for six months. Disease activity was determined by the SLE Disease Activity–2000 (SLEDAI-2K) scoring system and serum renalase amounts were determined by ELISA. Predictive value of renalase for disease activity was assessed. Furthermore, the expression of renalase in the kidneys of patients and macrophage infiltration was assessed by immunohistochemistry.

Results

Serum renalase amounts were significantly higher in LN patients than in healthy controls. Moreover, patients with proliferative LN had more elevated serum renalase levels than Class V LN patients. In proliferative LN patients, serum renalase levels were significantly higher in patients with active LN than those with inactive LN. Serum renalase levels were positively correlated with SLEDAI-2K, 24-h urine protein excretion, ds-DNA and ESR but inversely correlated with serum albumin and C3. Renalase amounts decreased significantly after six-months of standard therapy. The performance of renalase as a marker for diagnosis of active LN was 0.906 with a cutoff value of 66.67 μg/ml. We also observed that the amount of renalase was significantly higher in glomerular of proliferative LN along with the co-expression of macrophages.

Conclusion

Serum renalase levels were correlated with disease activity in LN. Serum renalase might serve as a potential indicator for disease activity in LN. The marked increase of glomerular renalase and its association with macrophages suggest that it might play an important role in disease progression of LN.     

Serum Levels of the Cancer-Testis Antigen POTEE and Its Clinical Significance in Non-Small-Cell Lung Cancer

Background

POTEE (POTE ankyrin domain family, member E) is a newly identified cancer-testis antigen that has been found to be expressed in a wide variety of human cancers including cancers of the colon, prostate, lung, breast, ovary, and pancreas.

Aim

To measure the serum levels of POTEE in patients with non-small-cell lung cancer (NSCLC) and to explore the clinical significance of POTEE in NSCLC.

Patients and Methods

104 NSCLC patients, 66 benign lung disease patients and 80 healthy volunteers were enrolled in this study from May 2013 to February 2014. Serum POTEE levels were measured using enzyme-linked immunosorbent assay (ELISA). Numerical variables were recorded as means ± standard deviation (SD) and analyzed by independent t tests. Categorical variables were calculated as rates and were analyzed using a χ² test or Fisher’s exact test. Survival curves were estimated and compared using the Kaplan-Meier method and log-rank tests.

Results

Serum POTEE levels were significantly higher in NSCLC patients than in benign lung disease patients and healthy controls (mean ± SD [pg/ml], 324.38± 13.84 vs. 156.93 ± 17.38 and 139.09 ± 15.80, P<0.001) and were significantly correlated with TNM stage. Survival analysis revealed that patients with low serum POTEE had longer progression-free survival (PFS) than those with high serum POTEE (P=0.021). Cox multivariate analysis indicated that POTEE was an independent prognostic factor of progression-free survival (P =0.009, hazard ratio, 2.440).

Conclusions

Serum POTEE level in NSCLC patients is associated with TNM stage and is a potential prognostic factor.     

Renal vein outflow recording in rats and rabbits: alternative method of R.B.F. measurement

A method is described for continuous measurement of total renal blood flow in anesthetized rats and rabbits. It consists of recording time intervals in which a fixed volume of renal vein outflow enters into an extracorporeal renin vein - jugular vein shunt and is pumped back to animals' circulation. This technique yields absolute flow values of unequalled accuracy and requires virtually no calibration; however, it is not suitable for recording rapid flow transients. The RBF measured averaged 5.5 +/- (SE) 0.1 ml/min.g kidney weight in rats and 2.5 +/- 1.1 ml/min.g in rabbits; the flow was stable over at least 1.5-2 hrs. The rat kidneys tested showed usual capacity to autoregulate blood flow during graded reduction in renal perfusion pressure.     

Australia (Hepatitis-Associated) Antigen in Patients Attending a Venereal Disease Clinic

A total of 1,650 patients attending the venereal disease department at St. Mary''s Hospital, London, have been tested for Australia antigen. Twenty-three positive results were obtained, or 1·39%, which is more than 10 times the rate noted by others in blood donor populations in the U.K. and U.S.A. The positive rates among female patients and European male heterosexual patients were 0·36% and 0·19% respectively. High rates were obtained for homosexual patients (3·8%) and non-European heterosexual patients (3·1%). The reasons for the higher rates found in these groups merit further study.     

Holding Thermal Receipt Paper and Eating Food after Using Hand Sanitizer Results in High Serum Bioactive and Urine Total Levels of Bisphenol A (BPA)

Bisphenol A (BPA) is an endocrine disrupting environmental contaminant used in a wide variety of products, and BPA metabolites are found in almost everyone’s urine, suggesting widespread exposure from multiple sources. Regulatory agencies estimate that virtually all BPA exposure is from food and beverage packaging. However, free BPA is applied to the outer layer of thermal receipt paper present in very high (∼20 mg BPA/g paper) quantities as a print developer. Not taken into account when considering thermal paper as a source of BPA exposure is that some commonly used hand sanitizers, as well as other skin care products, contain mixtures of dermal penetration enhancing chemicals that can increase by up to 100 fold the dermal absorption of lipophilic compounds such as BPA. We found that when men and women held thermal receipt paper immediately after using a hand sanitizer with penetration enhancing chemicals, significant free BPA was transferred to their hands and then to French fries that were eaten, and the combination of dermal and oral BPA absorption led to a rapid and dramatic average maximum increase (Cmax) in unconjugated (bioactive) BPA of ∼7 ng/mL in serum and ∼20 µg total BPA/g creatinine in urine within 90 min. The default method used by regulatory agencies to test for hazards posed by chemicals is intra-gastric gavage. For BPA this approach results in less than 1% of the administered dose being bioavailable in blood. It also ignores dermal absorption as well as sublingual absorption in the mouth that both bypass first-pass liver metabolism. The elevated levels of BPA that we observed due to holding thermal paper after using a product containing dermal penetration enhancing chemicals have been related to an increased risk for a wide range of developmental abnormalities as well as diseases in adults.     

Worse Renal Disease in Postmenopausal F2[Dahl S x R]-Intercross Rats: Detection of Novel QTLs Affecting Hypertensive Kidney Disease

The prevalence of hypertension increases after menopause with 75% of postmenopausal women developing hypertension in the United States, along with hypertensive end organ diseases. While human and animal model studies have indicated a protective role for estrogen against cardiovascular disease and glomerulosclerosis, clinical studies of hormone replacement therapy in postmenopausal women have shown polar results with some improvement in hypertension but worsening of hypertensive kidney disease, or no effect at all. These observations suggest that the pathogenesis of postmenopausal hypertension and its target organ complications is more complex than projected, and that loss of endogenous estrogens induces epigenetic changes that alter genetic susceptibility to end-organ complications per se resulting in pathogenetic mechanisms beyond correction by hormone replacement. We studied postmenopausal-induced changes in renal disease and performed a total genome scan for quantitative trait loci (QTLs) affecting kidney disease in postmenopausal 16m-old F2[Dahl S x R]-intercross female rats. We used glomerular injury score (GIS) as quantitative trait. We compared QTLs amongst premenopausal, ovariectomized and postmenopausal F2[Dahl S x R]-intercross rats using identical phenotype characterization. Postmenopausal F2[Dahl S x R]-intercross rats exhibited increased hypertensive glomerulosclerosis (P<0.01) and equivalent levels of kidney disease when compared to premenopausal and ovariectomized F2[Dahl S x R]-intercross rats respectively. We detected three significant to highly significant GIS-QTLs (GIS-pm1 on chromosome 4, LOD 3.54; GIS-pm2 on chromosome 3, LOD 2.72; GIS-pm3 on chromosome 5, LOD 2.37) and two suggestive GIS-QTLs (GIS-pm4 on chromosome 2, LOD 1.70; GIS-pm5 on chromosome 7, LOD 1.28), all of which were unique to this postmenopausal population. Detection of increased renal disease phenotype in postmenopausal and ovariectomized subjects suggests a protective role of ovarian hormones. Furthermore, the detection of distinct GIS-QTLs in postmenopausal intercross female rats suggests that distinct genetic mechanisms underlie hypertensive glomerulosclerosis in premenopausal and postmenopausal states.     

Disc-Agar Diffusion Microbiological Assay Procedure for Determining Serum and Urine Levels of Sulfacytine and Other Sulfonamides

A reasonably precise, reproducible, and sensitive microbiological procedure for directly assaying sulfacytine and other sulfonamides as antibacterially active drugs has been developed by appropriately modifying the standard disc-agar diffusion technique. Blood and urine levels as low as 3 mug/ml may be determined through the use of a strain of Escherichia coli and a chemically defined agar medium devoid of sulfonamide antagonists. Results indicate that this assay method should be a useful adjunct to the Bratton-Marshall colorimetric procedure, by permitting the direct measurement of antibacterially active drug in clinical specimens.