Prediction of urine volume soon after birth using serum cystatin C

Background

Urine volume is an important clinical finding particularly during the early neonatal period. Oliguria is not a sign of impaired renal function but also a predictive factor for various complications and prognoses. It has been postulated that serum cystatin C (S-CysC) is a more sensitive biomarker for renal function than serum creatinine (S-Cr) in both adults and children. The objective of the current study was to investigate whether urine volume during 24 h after birth can be predicted using S-CysC.

Methods

The subjects were 87 infants. The average gestational age was 34.7 ± 2.9 weeks and the average birth weight was 2135 ± 614 g. Blood samples were obtained from either the umbilical cord or the peripheral veins or artery of the newborn at birth. Data regarding the amount of urine volume and fluid intake during the first 24 h of life, maternal S-Cr and S-CysC levels within 48 h before delivery, and neonatal S-Cr and S-CysC levels at birth were collected from the medical records.

Results

A significantly positive correlation was observed between maternal and neonatal S-Cr levels (r = 0.84, p < 0.0001) but not between maternal S-Cr levels and neonatal S-CysC levels (r = ?0.069, p = 0.52). A significant negative correlation was seen between neonatal S-CysC levels and urine volume (r = ?0.47, p < 0.0001).

Conclusion

The present study findings indicate that it may be possible to use S-CysC levels at birth to predict urine volume during the first 24 h of life.

     

Re-evaluation of waist circumference in metabolic syndrome: a comparison between Japanese men and women

We re-evaluated the criteria for waist circumference to predict the accumulation of the components of metabolic syndrome. We used data for 3,185 Japanese, aged 20-79 years. Metabolic syndrome has recently been redefined by a new criterion in Japan, in which waist circumference cutoff points, i.e. 85 cm for men and 90 cm for women, are employed. Among the 3,185 Japanese considered in the present study, 335 men (26.8%) and 69 women (3.6%) were diagnosed as having metabolic syndrome. A cutoff point as a predictor for 2 or more components of metabolic syndrome was evaluated by sensitivity/specificity and a receiver operating characteristic (ROC) curve. The optimal point was estimated as being approximately 85 cm of waist circumference in men and 75 cm in women. We therefore recommend a cutoff value, 75 cm of waist circumference, for the criterion of metabolic syndrome in women.     

Extramural cancer deposits without nodal structure in colorectal cancer: optimal categorization for prognostic staging

To establish an optimal categorization of cancer deposits without lymph node structure (extranodal cancer deposits [EX]) in a prognostic staging system, we analyzed 1,027 cases in which patients underwent potentially curative surgery for advanced colorectal adenocarcinoma. EX was classified as vascular invasion-type (VAS) or non-VAS.A total of 512 foci of EX were identified in 205 patients (20.0%), with VAS and non-VAS found in 68 and 182 patients, respectively. The hazard ratio for patients with nodal involvement was 3.6 and for patients with VAS and non-VAS, 2.5 and 4.7, respectively. Based on multivariate analysis of these 3 parameters, only nodal involvement and non-VAS were significant prognosticators. By using the Akaike information criterion, N staging was capable of predicting survival outcome with the highest accuracy when both nodal involvement and non-VAS were treated together as an N factor and VAS was treated as a T factor ("new categorization"). The clinical significance of the TNM grading system for colorectal cancer would be enhanced if we treat EX as a new categorization.     

Evaluation of 4β-Hydroxycholesterol and 25-Hydroxycholesterol as Endogenous Biomarkers of CYP3A4: Study with CYP3A-Humanized Mice

Cytochrome P450 3A (CYP3A) enzymes metabolize approximately half of all drugs on the market. Since the endogenous compounds 4β-hydroxycholesterol (4β-HC) and 25-hydroxycholesterol (25-HC) are generated from cholesterol via CYP3A enzymes, we examined whether the plasma levels of 4β-HC and 25-HC reflect hepatic CYP3A4 activity by using a CYP3A-humanized mouse model, in which the function of endogenous Cyp3a was genetically replaced by human CYP3A. CYP3A-humanized mice have great advantages for evaluation of the relationship between hepatic CYP3A protein levels and plasma and hepatic levels of 4β-HC and 25-HC. Levels of CYP3A4 protein in the liver microsomes of CYP3A-humanized mice were increased by treatment with pregnenolone-16α-carbonitrile, a CYP3A inducer. Hepatic and plasma levels of 4β-HC and 25-HC normalized by cholesterol were significantly correlated with hepatic CYP3A4 protein levels. In addition, in vitro studies using human liver microsomes showed that the formation of 4β-HC was strongly inhibited by a CYP3A inhibitor, while the inhibitory effect of the CYP3A inhibition on the formation of 25-HC was weak. These results suggested that CYP3A mainly contributed to the formation of 4β-HC in human liver microsomes, whereas other factors may be involved in the formation of 25-HC. In conclusion, the in vivo studies using CYP3A-humanized mice suggest that plasma 4β-HC and 25-HC levels reflect hepatic CYP3A4 activity. Furthermore, taking the results of in vitro studies using human liver microsomes into consideration, 4β-HC is a more reliable biomarker of hepatic CYP3A activity.     

Immunosuppressive and metabolic agents that influence allo- and xenograft survival by in vivo expansion of T regulatory cells

The transplanted organs or cells survive if the recipient receives adequate long-term immunosuppressive therapy. Immunosuppressive therapy combined with cell-based strategies (eg, regulatory T cell [Treg]-based therapy) promotes graft survival. A combination of Treg-based therapy and minimal or no immunosuppressive drug therapy would have the potential to minimize the risks of the complications and side effects of these drugs. Fortunately, some immunosuppressive and other agents not only impede the effector T cell response, but also help generate new CD4⁺ Tregs from conventional effector T cells. These agents include IL-2, TGF-β, agents that block the CD40/CD40L costimulation pathway, mTOR inhibitors, and histone deacetylase inhibitors. Consequently, a state of relative unresponsiveness to the transplanted organ may be induced through the expansion of Tregs. We here review the effect of these various agents on expansion of CD4⁺ Tregs in allo- and xenotransplantation. The expansion of Tregs might allow a dose reduction of the standard immunosuppressive drugs.     

Interaction between gastric cancer stem cells and the tumor microenvironment

Gastric cancer (GC) remains a leading cause of cancer-related deaths worldwide. Cancer stem cells (CSCs) are selectively capable of tumor initiation and are implicated in tumor relapse and metastasis, thus, governing the prognosis of GC patients. Stromal cells and extracellular matrix adjacent to cancer cells are known to form a supportive environment for cancer progression. CSC properties are also regulated by their microenvironment through cell signaling and related factors. This review presents the current findings regarding the influence of the tumor microenvironment on GC stem cells, which will support the development of novel therapeutic strategies for patients with GC.