Perinatal mortality in Japanese women diagnosed with gestational diabetes mellitus and diabetes mellitus.

AIMS: The objective of this study was to determine how many pregnant Japanese women with diabetes mellitus (DM)/gestational diabetes mellitus (GDM) experience perinatal mortality in the presence of fetal anomalies. METHODS: Our investigation included data from 205 secondary/tertiary obstetric facilities located widely in Japan. The Japan Ministry of Health, Labour and Welfare Vital Statistics of Japan was used for comparison. RESULTS: Of 237 941 women giving birth at 205 hospitals, 1796 (0.8%) and 13 037 (5.5%) had DM and GDM, respectively. The perinatal mortality rates (per 1000 births) were 10.6 (19/1796) for women with DM, 5.2 (68/13037) for women with GDM, and 3.7 (7612/2039504) for the general Japanese population. Detailed information was available for 63 (72%) of the 87 perinatal deaths occurring in women with diabetes including DM and GDM; fetal anomalies were associated with 40% (25/63) of perinatal deaths, exceeding 16% (1211/7612) in the general Japanese population (P < 0.0001). The leading four fetal anomalies associated with perinatal mortality in women with diabetes were fetal trisomy (6 cases: 1 of trisomy-13 and 5 of trisomy-18), non-immune hydrops fetalis (5 cases), cardiac deformities (3 cases) and holoprosencephaly (2 cases). CONCLUSIONS: Perinatal mortality was more likely to occur in women with glucose intolerance. In the Japanese infants that succumbed to perinatal mortality, fetal anomaly was more prevalent in those born to women with a glucose intolerance than in those born to the general population.

Hemoglobin Glycation Index: A Novel Risk Factor for Incident Chronic Kidney Disease in an Apparently Healthy Population.

CONTEXT: Chronic kidney disease (CKD) is a worldwide health problem. Recent literature has shown an association of hemoglobin glycation index (HGI) and CKD in patients with dysglycemia. OBJECTIVE: The aim of this study was to reveal the impact of HGI as a predictor for incident CKD in the general population. METHODS: CKD was defined as dipstick proteinuria or estimated glomerular rate (eGFR) < 60 mL/min/1.73 m2. Impact of HGI on incident CKD was assessed using the data from CKD-free health examinees (N = 23 467, 4.1% with diabetes) followed for a mean of 5.1 years: Cox proportional hazards model was employed with multivariate adjustment for age, systolic blood pressure, eGFR, fasting plasma glucose, body mass index, log[alanine aminotransferase], log[triglycerides], high-density lipoprotein cholesterol, platelet counts, smoking, and sex. Elevated level of HGI in subjects with CKD was ascertained after propensity score matching of another group of health examinees (N = 2580, 7.6% with diabetes). RESULTS: In the former group, CKD developed in 2540 subjects and HGI was the second most robust predictor for CKD, following low eGFR. With adjustment for the 11 covariates, the hazard ratio of HGI (95% CI) for CKD was 1.293 (1.238 to 1.349) (P < .0001). The population attributable risk of HGI for CKD was 4.2%. In the latter group, among 708 subjects matched 1:1 for 9 covariates, HGI was significantly elevated in subjects with CKD (median [interquartile range] -0.208 [-0.504 to -0.156] vs -0.284 [-0.582 to 0.052], P = .03). CONCLUSION: HGI was a novel risk factor for CKD in the general population.

A local anesthetic, ropivacaine, suppresses activated microglia via a nerve growth factor-dependent mechanism and astrocytes via a nerve growth factor-independent mechanism in neuropathic pain.

BACKGROUND: Local anesthetics alleviate neuropathic pain in some cases in clinical practice, and exhibit longer durations of action than those predicted on the basis of the pharmacokinetics of their blocking effects on voltage-dependent sodium channels. Therefore, local anesthetics may contribute to additional mechanisms for reversal of the sensitization of nociceptive pathways that occurs in the neuropathic pain state. In recent years, spinal glial cells, microglia and astrocytes, have been shown to play critical roles in neuropathic pain, but their participation in the analgesic effects of local anesthetics remains largely unknown. RESULTS: Repetitive epidural administration of ropivacaine reduced the hyperalgesia induced by chronic constrictive injury of the sciatic nerve. Concomitantly with this analgesia, ropivacaine suppressed the increases in the immunoreactivities of CD11b and glial fibrillary acidic protein in the dorsal spinal cord, as markers of activated microglia and astrocytes, respectively. In addition, epidural administration of a TrkA-IgG fusion protein that blocks the action of nerve growth factor (NGF), which was upregulated by ropivacaine in the dorsal root ganglion, prevented the inhibitory effect of ropivacaine on microglia, but not astrocytes. The blockade of NGF action also abolished the analgesic effect of ropivacaine on neuropathic pain. CONCLUSIONS: Ropivacaine provides prolonged analgesia possibly by suppressing microglial activation in an NGF-dependent manner and astrocyte activation in an NGF-independent manner in the dorsal spinal cord. Local anesthetics, including ropivacaine, may represent a new approach for glial cell inhibition and, therefore, therapeutic strategies for neuropathic pain.

Premenstrual disappearance of aminopeptidase A in endometrial stromal cells around endometrial spiral arteries/arterioles during the decidual change.

Aminopeptidase A (APA, BP-1) is a membrane-bound zinc metallopeptidase that converts angiotensin II (AngII) into AngIII by selectively hydrolyzing the N-terminal aspartyl residue. AngII has been proposed as a candidate for the initial vasoconstrictor of endometrial spiral arteries/arterioles in the preliminary step of menstruation. In the late secretory phase, endometrial stromal cells (ESC) around the blood vessels begin to differentiate into decidual cells, and AngII has been reported to accumulate around such vessels. However, whether there is a concurrent increase in renin or angiotensin-converting enzyme in this area has not been determined. We hypothesized that APA may be involved in the metabolism of AngII in the cycling endometrium. Western blot analysis in the present study demonstrated that a considerable amount of APA was present in the secretory phase endometrium. ESC in the secretory phase showed strong expression of APA by immunohistochemical analysis and of APA mRNA by in situ hybridization. In contrast, both APA mRNA and protein were absent in decidual cells. The enzyme activity and the biosynthesis of [(35)S]methionine-labeled APA significantly decreased during the in vitro decidualization of cultured ESC. These results suggest that the perivascular disappearance of APA is a differentiation-specific change that occurs along with the decidualization, and that the disappearance of APA might accelerate the accumulation of AngII around the vessels.

Existence of placental leucine aminopeptidase/oxytocinase/insulin-regulated membrane aminopeptidase in human endometrial epithelial cells.

Human endometrial epithelial cells are known to express oxytocin receptors around the time of ovulation. Moreover, oxytocin (OT) and OT-induced prostaglandins appear to play a pivotal role in the switching of endometrial glands from the proliferative to the secretory phase. However, there have been few studies of oxytocinase (OTase), which is identical to placental leucine aminopeptidase (P-LAP)/insulin-regulated membrane aminopeptidase (IRAP). We confirmed the expression of P-LAP/OTase in human endometrium and also observed the changes in the expression of P-LAP/OTase throughout the menstrual cycle. P-LAP/OTase and its mRNA were localized in endometrial epithelial cells but not in stromal cells. In the follicular phase, immunoreactive P-LAP/OTase was homogeneously distributed on the plasma membrane and in cytoplasmic granules. Immunoblot analysis demonstrated that the majority of P-LAP/OTase was produced around the time of ovulation. After ovulation, the immunostaining was restricted to the glycogen-rich subnuclear vacuoles, a glandular marker of progesterone release from the corpus luteum. Thereafter, the membrane-bound P-LAP/OTase was released by apocrine secretion during the period of blastocyst implantation and became depleted toward the time of menstruation. Further understanding of the function of P-LAP/OTase in the endometrium appears likely to yield insights into the cyclic changes during the normal menstrual cycle.

Direct hemoperfusion with a beta2-microglobulin-selective adsorbent column eliminates inflammatory cytokines and improves pulmonary oxygenation.

Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are characterized by a high mortality rate; therefore, ARDS/ALI in humans is a leading cause of morbidity and mortality in critically ill patients. As previously reported, cytokines play a critical role as signaling molecules that initiate, amplify, and perpetuate inflammatory responses on a local and systemic basis, and the polymyxin-B immobilized direct hemoperfusion system (PMX-DHP) is effective for the treatment of ARDS/ALI. Furthermore, another direct hemoperfusion system using the beta2-microglobulin-selective adsorbent column, Lixelle, the direct hemoperfusion treatment (Lixelle-DHP), has been applied in some cases to patients who are affected with systemic inflammatory response syndrome. The aim of this study is to evaluate the therapeutic efficacy of Lixelle-DHP in the treatment of ARDS/ALI. Four patients, aged 67-79 years old (mean 72 +/- 6.2 years), diagnosed with ARDS/ALI were treated with Lixelle-DHP. The P(a)O(2)/fraction of inspired oxygen (F(i)O(2)) ratio (PF ratio) was 90.0 +/- 22.9 before the treatment, and it increased to 129.9 +/- 5.6 at 72 h afterward the start of treatment. Inflammatory cytokines such as interleukin (IL)-1 beta, IL-6, soluble intercellular adhesion molecule 1 (sICAM-1) decreased significantly after the treatment. All patients were still alive after one month. However, while IL-2 had decreased significantly after the treatment, it had returned by the next treatment. It is possible that Lixelle-DHP might be able to improve the PF ratio and mortality rate as a result of decreased cytokines, and it has been suggested that Lixelle-DHP has a beneficial influence in the treatment of ARDS/ALI.

Oral progestogen versus intramuscular progesterone for luteal support after assisted reproductive technology treatment: a prospective randomized study.

OBJECTIVES: To evaluate the efficacy of oral progestogen, chlormadinone acetate, and intramuscular (IM) progesterone for luteal support in patients, undergoing assisted reproductive technology (ART) treatment, who were treated with a gonadotropin-releasing hormone agonist (GnRHa). METHODS: This was a prospective randomized study of 40 patients with normal and high response (serum estradiol > 2,000 pg/ml) in GnRHa down-regulation. Patients were randomized to receive either oral chlormadinone acetate or IM progesterone. The outcomes of ART treatment, including pregnancy and embryo implantation rates, were analyzed. RESULTS: There were no significant differences in the clinical pregnancy rates (25 vs. 20%) and in the implantation rates (12.7 vs. 9.1%) of patients who received IM progesterone and oral chlormadinone acetate. Endometrial thickness was also comparable between oral chlormadinone acetate and IM progesterone. CONCLUSION: Oral progestogen, chlormadinone acetate showed a comparable pregnancy rate and live birth rate with IM progesterone as luteal support for the high responders. The optimal methods for luteal support may be dependent on responses to stimulation with gonadotropin, although it is not concluded that oral chlormadinone acetate is recommended as an option for luteal support in high responders.