Cystatin-C as a Marker for Renal Impairment in Preeclampsia

Preeclampsia is a devastating pregnancy-associated disorder characterized by the onset of hypertension, proteinuria, and edema with limited plausible pathophysiology known. Cystatin-C, a novel marker for the detection of renal impairment, is increased in preeclampsia at an early stage. This study was aimed to evaluate the diagnostic efficiency of Cystatin-C as an early marker of renal function in preeclampsia comparing it to the traditional renal markers. A hospital based comparative cross-sectional study was performed on 104 women (52 diagnosed cases of preeclampsia and 52 healthy pregnant women). Concentrations of Cystatin-C, creatinine, urea, and uric acid were measured in both the study groups. Mean serum Cystatin-C and uric acid levels were elevated in preeclampsia cases compared to controls (1.15 ± 0.37 versus 0.55 ± 0.12; 5.40 ± 1.44 versus 3.97 ± 0.68, resp.). ROC curve depicted that Cystatin-C had the highest diagnostic efficiency (sensitivity, 88.24%; specificity, 98.04%) compared to creatinine and uric acid. Serum Cystatin-C consequently seemed to closely reflect the renal functional changes, which are believed to lead to increased blood pressure levels and urinary excretion of albumin and may thus function as a marker for the stage of the transition between normal adaptive renal changes at term and preeclampsia.

The Circadian Rhythm of Copeptin, the C-Terminal Portion of Arginine Vasopressin

Background. Several studies have investigated copeptin as a prognostic marker of different acute diseases and as a diagnostic marker in disorders of water and salt homeostasis. However, no data of the normal circadian rhythm of copeptin in healthy subjects are available. Aim. To investigate the circadian rhythm of copeptin in healthy subjects under standardized conditions. Methods. 19 healthy volunteers aged 18 to 53 years, male and female, were studied in a prospective observational study. In all 19 participants, blood samples for copeptin were taken in regular intervals of 30 minutes for 24 hours after a fasting period of minimum 8 hours. Results. The mean values of copeptin showed a circadian rhythm, similar to that described for AVP release, with a trend towards higher levels (5.9±1 pmol/L) at night and early morning between 4 am and 6 am and lowest levels (2.3±0.2 pmol/L) in the late afternoon between 5 pm and 7 pm. This finding was only observed in individuals with initial higher copeptin levels, whereas in individuals with lower basal copeptin levels no circadian rhythm was observed. Conclusion. There is evidence for a circadian rhythm in copeptin release during 24 hours, however, of minor extent. These findings suggest that copeptin levels can be determined irrespectively of the time of the day.

Body Mass Index, Haemoglobin, and Total Lymphocyte Count as a Surrogate for CD4 Count in Resource Limited Settings

Background. In view of the lack of evidence on the possibility of an economically viable, easy, and readily available biomarker to substitute the traditional role of CD4 counts in HIV disease progression, this study seeks to investigate the potential use of body mass index (BMI), haemoglobin (Hb), and total lymphocyte count (TLC) as surrogate biomarkers for monitoring the disease. Methods. This cross-sectional study was undertaken at the antiretroviral clinic (ART) of the Bomso Hospital, Kumasi, Ghana. We recruited 384 individuals who were 18 years or older and confirmed HIV seropositive patients. Blood samples were assayed for TLC and Hb. Weight and height were determined and BMI was calculated. Result. At a cut-off point of 12.15 g/dL, Hb had sensitivity and specificity of 73.9% and 56.8%, respectively, whereas BMI had 69.6% and 80.1% sensitivity and specificity, respectively. The sensitivity and specificity were also 100% among the studied participants at a cut-off point of 1200 mm−3 for TLC. There was a significant positive correlation between CD4 count and Hb (rho 0.262, p=0.0001), BMI (rho 0.301, p=0.0001), and TLC (rho 0.834, p=0.0001). Conclusion. The study demonstrates that TLC, Hb, and BMI may provide some useful prognostic information independent of that provided by CD4 count.

The Diagnostic Value of Serum C-Reactive Protein for Identifying Pneumonia in Hospitalized Patients with Acute Respiratory Symptoms

Background. The clinical diagnosis of pneumonia is sometimes difficult since chest radiographs are often indeterminate. In this study, we aimed to assess whether serum C-reactive protein (CRP) could assist in identifying patients with pneumonia. Methods. For one winter, all consecutive patients with acute respiratory symptoms admitted to the emergency ward of a single center were prospectively enrolled. In addition to chest radiographs, basic laboratory tests, and microbiology, serum levels of CRP were measured at entry. Results. A total of 923 (62.3%) of 1473 patients hospitalized for acute respiratory symptoms were included. Subjects with a final diagnosis of pneumonia had higher serum CRP levels (median 187 mg/L) than those with exacerbations of chronic obstructive pulmonary disease (63 mg/L) or acute bronchitis (54 mg/L, p<0.01). CRP was accurate in identifying pneumonia (area under the curve 0.84, 95% CI 0.82–0.87). The multilevel likelihood ratio (LR) for intervals of CRP provided useful information on the posttest probability of having pneumonia. CRP intervals above 200 mg/L were associated with LR+ > 5, for which pneumonia is likely, whereas CRP intervals below 75 mg/L were associated with LR < 0.2, for which pneumonia is unlikely. Conclusion. Serum CRP may be a useful addition for diagnosing pneumonia in hospitalized patients with acute respiratory symptoms.

The Predictive Role of Inflammatory Biomarkers in Atrial Fibrillation as Seen through Neutrophil-Lymphocyte Ratio Mirror

Atrial fibrillation (AF) is the most common arrhythmia and is responsible for significant disease burden worldwide. Current evidence has suggested that systemic inflammatory response plays a crucial role in the initiation, maintenance, and progression of AF. So, recent efforts have been directed in search of measurable inflammatory biomarkers as additional tools in severity and prognosis assessment of AF. A simple, and easily obtainable, inflammatory marker is the neutrophil-lymphocyte ratio (NLR), which has shown good performance in preliminary studies as a potential prognostic biomarker in patients with AF. In this work, we performed a thorough review of clinical studies that evaluated the role of C-reactive protein (CRP), interleukin-6 (IL-6), and NLR as predictors of outcomes in AF. We gave a particular emphasis on the NLR because it is a simpler, widely available, and inexpensive biomarker.

Determination of Urinary Neopterin/Creatinine Ratio to Distinguish Active Tuberculosis from Latent Mycobacterium tuberculosis Infection

Background. Biomarkers to distinguish latent from active Mycobacterium (M.) tuberculosis infection in clinical practice are lacking. The urinary neopterin/creatinine ratio can quantify the systemic interferon-gamma effect in patients with M. tuberculosis infection. Methods. In a prospective observational study, urinary neopterin levels were measured by enzyme linked immunosorbent assay in patients with active tuberculosis, in people with latent M. tuberculosis infection, and in healthy controls and the urinary neopterin/creatinine ratio was calculated. Results. We included a total of 44 patients with M. tuberculosis infection and nine controls. 12 patients had active tuberculosis (8 of them culture-confirmed). The median age was 15 years (range 4.5 to 49). Median urinary neopterin/creatinine ratio in patients with active tuberculosis was 374.1 micromol/mol (129.0 to 1072.3), in patients with latent M. tuberculosis infection it was 142.1 (28.0 to 384.1), and in controls it was 146.0 (40.3 to 200.0), with significantly higher levels in patients with active tuberculosis (p<0.01). The receiver operating characteristics curve had an area under the curve of 0.84 (95% CI 0.70 to 0.97) (p<0.01). Conclusions. Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection.

Association Study between Promoter Polymorphism of TPH1 and Progression of Idiopathic Scoliosis

The concept of disease-modifier genes as an element of genetic heterogeneity has been widely accepted and reported. The aim of the current study is to investigate the association between the promoter polymorphism TPH1 (rs10488682) and progression of idiopathic scoliosis (IS) in Eastern European population sample. A total of 105 patients and 210 healthy gender-matched controls were enrolled in this study. The TPH1 promoter polymorphism was genotyped by amplification followed by restriction. The statistical analysis was performed by Fisher’s Exact Test. The results indicated that the genotypes and alleles of TPH1 (rs10488682) are not correlated with curve severity, curve pattern, or bracing. Therefore, the examined polymorphic variant could not be considered as a genetic factor with modifying effect of IS. In conclusion, this case-control study revealed no statistically significant association between TPH1 (rs10488682) and progression of IS in Eastern European population sample. These preliminary results should be replicated in extended population studies including larger sample sizes. The identification of molecular markers for IS could be useful for a more accurate prognosis of the risk for a rapid progression of the curve. That would permit early stage treatment of the patient with the least invasive procedures.

A Sensitive IHC Method for Monitoring Autophagy-Specific Markers in Human Tumor Xenografts

Objective. Use of tyramide signal amplification (TSA) to detect autophagy biomarkers in formalin fixed and paraffin embedded (FFPE) xenograft tissue. Materials and Methods. Autophagy marker regulation was studied in xenograft tissues using Amp HQ IHC and standard IHC methods. Results. The data demonstrate the feasibility of using high sensitivity TSA IHC assays to measure low abundant autophagy markers in FFPE xenograft tissue.

Association of Plasma Heat Shock Protein 70, Interleukin 6, and Creatine Kinase Concentrations in a Healthy, Young Adult Population

Variations of baseline plasma concentrations of creatine kinase (CK), heat shock protein 70 (HSP70), and interleukin 6 (IL-6) have been reported. We report categorical associations which may influence these protein levels. Methods. Blood was harvested for DNA and plasma protein analysis from 567 adults. Mean protein levels of CK, HSP70, and IL-6 were compared by sex, ethnicity, genetic variants—CKMM Nco1 (rs1803285), HSPA1B +A1538G (rs1061581), and IL6 G-174C (rs1800795)—self-reported history of exercise, oral contraceptive use, and dietary supplement use. Results. SNP major allele frequencies for CKMM, HSPA1B, and IL6 were 70% A, 57% A, and 60%. Mean CK statistically differed by sex, ethnicity, oral contraceptives, and caffeine. Plasma HSP70 differed by caffeine and protein. Mean IL-6 concentration differed by sex, ethnicity, and genotype. Plasma IL-6 was significantly lower (29%) in males (1.92 ± 0.08 pg/mL) and higher (29%) among African Americans (2.85 ± 0.50 pg/mL) relative to the others. IL6 G-174C GG genotype (2.23 ± 0.14 pg/mL) was 19% greater than CG or CC genotypes. Conclusion. Differences in baseline CK and IL-6 plasma protein concentrations are associated with genetics, sex, ethnicity, and the use of oral contraceptives, caffeine, and protein supplements in this young and athletic population.