Involvement of the Restoration of Cerebral Blood Flow and Maintenance of eNOS Expression in the Prophylactic Protective Effect of the Novel Ferulic Acid Derivative FAD012 against Ischemia/Reperfusion Injuries in Rats.

Tissue plasminogen activator, aiming to restore cerebral blood flow (CBF), has been used for acute ischemic strokes in clinics; however, its narrow therapeutic time window remains a serious concern. To develop novel prophylactic drugs to alleviate cerebral ischemia/reperfusion injuries, ferulic acid derivative 012 (FAD012) was synthesized and showed comparable antioxidant properties to ferulic acid (FA) and probably possesses the potent ability to cross the blood-brain barrier. A more potent cytoprotective effect of FAD012 against H2O2-induced cytotoxicity in PC12 cells was also observed. In vivo toxicity was not observed in rats given a long-term oral administration of FAD012, indicating its good tolerability. A one-week-course oral administration of FAD012 significantly alleviated middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injuries in rats, accompanied by the restoration of CBF and endothelial nitrogen oxide synthetase (eNOS) expression. Treatment with FAD012 significantly restored the cell viability and eNOS expression damaged by H2O2, used to mimic MCAO-triggered oxidative stress, in rat brain microvascular endothelial cells. Our findings suggested that FAD012 protected the viability of vascular endothelium and maintained eNOS expression, ultimately contributing to the restoration of CBF, and may provide a rationale for the development of FAD012 into an effective prophylactic drug for patients at high risk of stroke.

Robot-assisted anterior resection for rectal cancer with double inferior vena cava: A case report.

Double inferior vena cava (DIVC) is a rare but generally asymptomatic condition that is often detected incidentally by radiological examinations such as computed tomography (CT). Here, we describe the case of a 73-year-old woman with DIVC, who underwent robot-assisted surgery (RS) for rectal cancer. In this case, 3D CT angiography showed DIVC with an interiliac vein from the left common iliac vein and a tortuous aorta. Intraoperatively, we identified the presence of the left IVC in addition to the inferior mesenteric vein, gonadal vein, and ureter, which require meticulous attention during vascular processing. By optimizing the port placement, we were able to ensure mobility of the robotic arm and sufficient field of view to safely perform a robot-assisted anterior resection with lymph node dissection. Careful preoperative assessment and development of a strategy for port placement using CT imaging are essential in avoiding iatrogenic injury and performing safe RS.

Robotic low anterior resection of rectal metastasis from small bowel adenocarcinoma: A case report.

A 69-year-old female underwent laparoscopic ileal partial resection for ileal adenocarcinoma. Pathological diagnosis was moderately differentiated tubular adenocarcinoma (UICC 8th; T4N0M0 StageIIB). The patient received adjuvant chemotherapy with modified 5-fluorouracil/leucovorin/oxaliplatin. Fourteen months after surgery, computed tomography revealed a mass in the upper rectum. Colonoscopy detected a submucosal protruding mass and a biopsy specimen showed moderately differentiated tubular adenocarcinoma. Robotic low anterior resection was performed. The tumor was located in the upper rectum and there was no macroscopic invasion or peritoneal dissemination. Pathologically, the tumor was moderately differentiated tubular adenocarcinoma located within the rectal wall with little evidence of a carcinoma component in the mucosal lining. Immunohistochemistry showed the same pattern as the previous ileal adenocarcinoma: negativity for cytokeratin 7 and positivity for cytokeratin 20 and caudal-type homeobox 2. In combination with the rectum showing no abnormalities in colonoscopy performed 15 mo previously, the mass was considered hematogenous metastasis from small bowel adenocarcinoma.

Laparoscopic resection of a gastrointestinal stromal tumor that recurred more than 15 years after surgery using lighted ureteral catheters: A case report.

A 69-year-old woman underwent abdominoperineal resection for a gastrointestinal stromal tumor (GIST) of the rectum 15 years ago. She received adjuvant chemotherapy for 8 years. Seven years later, abdominal computed tomography revealed a soft-tissue shadow in the left lower abdomen, and fluorodeoxyglucose uptake was observed at the same site on positron emission tomography. The recurrence of GIST was suspected, and laparoscopic resection was performed. Laparoscopy showed that the tumor was located at the retroperitoneum near to the descending colon and invaded the left ovarian vessels. It also made contact with the left ureter; however, lighted ureteral catheters enabled us to identify and preserve the left ureter. An immunohistochemical examination revealed the recurrence of GIST. Recurrence may become apparent 15 years or more after GIST surgery, and, thus, a long-term follow-up is required. Lighted ureteral catheters were useful for identifying the ureter and preventing ureteral injury in a recurrent case suspected of invading the ureter.

Niclosamide affects intracellular TDP-43 distribution in motor neurons, activates mitophagy, and attenuates morphological changes under stress.

Amyotrophic lateral sclerosis (ALS) is characterized by progressive motor neuron loss in the brain and spinal cord; however, its etiology is unknown, and no curative treatment exists. TAR DNA-binding protein 43 (TDP-43), encoded by TARDBP, is a genetic mutation observed in 2-5% of familial ALS, and TDP is known to be mislocalized in the cytoplasm. This study aimed to identify compounds that inhibited the nuclear to cytoplasmic localization of TDP-43 in human induced pluripotent stem (iPS) cells-derived neurons. TDP-43 transgenic human iPS cells were constructed, differentiated into motor neurons, and then treated with MG-132 and sodium arsenite (stressors) to induce nuclear to cytoplasmic localization of TDP-43. STAT3 inhibitors, such as niclosamide, prevented TDP-43 mislocalization and degraded TDP-43 aggregates, and attenuated morphological changes under stress. Furthermore, niclosamide activated mitophagy via the PINK1-parkin-ubiquitin pathway. These findings suggest niclosamide may be a therapeutic candidate for ALS.

Laparoscopic treatment for celiac artery stenosis caused by median arcuate ligament compression with Adachi V type vascular anomaly: a case report.

BACKGROUND: Median arcuate ligament syndrome (MALS), which results from compression of the median arcuate ligament (MAL), is a rare cause of abdominal pain and weight loss. Treatment is dissection of the MAL; however, the laparoscopic procedure is not yet established and it involves the risk of major vascular injury, especially in cases with an anomaly. CASE PRESENTATION: A 47-year-old man was evaluated at the hospital for epigastric pain. Contrast computed tomography scan revealed stenosis of the celiac artery origin due to the MAL. An Adachi V type vascular anomaly was also observed. Laparoscopic treatment was performed to release pressure on the celiac artery. Laparoscopic ultrasonography was used to less invasively confirm the release of the MAL. Despite a concomitant Adachi V type vascular anomaly, surgery was safely performed using the laparoscopic magnification view and intraoperative ultrasonography. Follow-up ultrasonography confirmed the celiac artery stenosis has not recurred. CONCLUSIONS: A rare case of MALS with an Adachi V type vascular anomaly is presented and the laparoscopic treatment is detailed.

Characterization of 6-bromoferulic acid as a novel common-use matrix for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

RATIONALE: Ferulic acid (FA) is a standard matrix used for analyzing proteins. In this study, the ability of a halogenated FA to serve as an effective MALDI matrix was investigated. Various halogenated FAs were synthesized, and the characteristics and performance of each were compared with those of the standard matrices α-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydrobenzoic acid (DHBA). METHODS: The abilities of 6-bromoferulic acid (6-BFA), ferulic acid (FA), and eight other halogenated FA derivatives to ionize eight synthetic peptides were examined. Absorption measurements, MM2 structure optimizations, and proton affinity (PA) calculations were also performed for 6-BFA and FA. The suitabilities of these compounds as matrices for matrix-assisted laser desorption/ionization (MALDI) for lipids, sugar chains, polymers, cyanocobalamin, synthetic peptides, and tryptic peptides originating from two types of serum proteins were also tested. RESULTS: The 6-position of FA was found to be the best site for introducing a bromine because the generated compound allowed facile detection of cyanocobalamin and several peptides. 6-BFA exhibited good sensitivity for large peptides (3-5 kDa) and peptides containing acidic amino acids or proline. 6-BFA was also shown to be a suitable matrix for tandem mass spectrometry (MS/MS) analysis when using MALDI time-of-flight (TOF) mass spectrometry (MS) with a quadrupole ion trap (QIT) system. CONCLUSIONS: The properties of 6-BFA as a MALDI matrix differed from those of DHBA and CHCA. 6-BFA appears to be a useful matrix for de novo sequencing using MALDI-QIT-TOF-MS.

Laparoscopic repair of a large perineal hernia after laparoscopic abdominoperineal resection: A case report.

A 75-year-old woman underwent laparoscopic abdominoperineal resection. Four months after abdominoperineal resection, the patient complained of a perineal bulge and urination disorder. Abdominal CT showed protrusion of the small intestine and bladder to the perineum. The patient underwent laparoscopic hernia repair with mesh. The size of the hernial orifice was 7.0 × 9.0 cm, and it had no solid rim. The mesh was tacked ventrally to the pectineal ligament and dorsally to the sacrum, and then sutured on the lateral side. The hernia has not recurred 10 months after the operation. Laparoscopic repair is a good treatment choice for secondary perineal hernia and fixing the mesh to the pectineal ligament, and the sacrum prevents the mesh from sagging.

Anticipation of umbistoma in laparoscopic anterior rectal resection: Ileostomy and ostomy closure.

OBJECTIVE: The use of laparoscopic surgery for rectal disease is expected to provide good cosmetic benefits for patients postoperatively. However, this expectation is significantly reduced when a diverting ileostomy is created. We present a new technique that reduces the size of the skin wound by constructing a diverting ileostomy in the umbilicus. This procedure, diverting umbilical ileostomy (umbistoma) does not require special tools for its construction and closure. METHODS: Twenty-nine patients underwent treatment with umbilical diverting stoma, including five women and 24 men, with a mean age of 70 years (range: 40-88 years). At the time of ostomy closure, a new umbilicus was formed by subcutaneously suturing the wound to the fascia. In addition, we did not close the new umbilical upper and lower spaces, so as to allow open drainage of the healing wound. RESULTS: All procedures were completed successfully without any perioperative complications. CONCLUSIONS: Our findings suggest that the umbilical diverting stoma could provide improved safety and cosmetic advantages in laparoscopic rectal resection.

A case of a mucin-producing bile duct tumor diagnosed over the course of 6 years.

We report a case of a mucin-producing intraductal papillary neoplasm of the intrahepatic bile duct (M-IPNB) diagnosed over a period of 6 years. A 64-year-old man underwent follow-up evaluations for an abdominal aortic aneurysm at our hospital. In 2009, a computed tomography (CT) scan revealed a simple hepatic cyst in segment 3 of the liver. Annual CT scans initially showed almost no change in the size or shape of the cyst. The cystic lesion, which measured 5 cm in 2014, had increased to 11 cm by 2015, and a solid component was detected within the cyst. A biliary cystic tumor was suspected and we performed a left lateral hepatectomy. Pathological examination showed that the papillary lesion in the cyst included adenocarcinoma and adenoma components. We diagnosed M-IPNB in 2015. Identification of the solid component of the cyst, as well as an increase in cyst diameter in the image analyses, was critical for diagnosis of M-IPNB.

Differentiation of oligodendrocyte progenitor cells from dissociated monolayer and feeder-free cultured pluripotent stem cells.

Oligodendrocytes myelinate axons and form myelin sheaths in the central nervous system. The development of therapies for demyelinating diseases, including multiple sclerosis and leukodystrophies, is a challenge because the pathogenic mechanisms of disease remain poorly understood. Primate pluripotent stem cell-derived oligodendrocytes are expected to help elucidate the molecular pathogenesis of these diseases. Oligodendrocytes have been successfully differentiated from human pluripotent stem cells. However, it is challenging to prepare large amounts of oligodendrocytes over a short amount of time because of manipulation difficulties under conventional primate pluripotent stem cell culture methods. We developed a proprietary dissociated monolayer and feeder-free culture system to handle pluripotent stem cell cultures. Because the dissociated monolayer and feeder-free culture system improves the quality and growth of primate pluripotent stem cells, these cells could potentially be differentiated into any desired functional cells and consistently cultured in large-scale conditions. In the current study, oligodendrocyte progenitor cells and mature oligodendrocytes were generated within three months from monkey embryonic stem cells. The embryonic stem cell-derived oligodendrocytes exhibited in vitro myelinogenic potency with rat dorsal root ganglion neurons. Additionally, the transplanted oligodendrocyte progenitor cells differentiated into myelin basic protein-positive mature oligodendrocytes in the mouse corpus callosum. This preparative method was used for human induced pluripotent stem cells, which were also successfully differentiated into oligodendrocyte progenitor cells and mature oligodendrocytes that were capable of myelinating rat dorsal root ganglion neurons. Moreover, it was possible to freeze, thaw, and successfully re-culture the differentiating cells. These results showed that embryonic stem cells and human induced pluripotent stem cells maintained in a dissociated monolayer and feeder-free culture system have the potential to generate oligodendrocyte progenitor cells and mature oligodendrocytes in vitro and in vivo. This culture method could be applied to prepare large amounts of oligodendrocyte progenitor cells and mature oligodendrocytes in a relatively short amount of time.

Laparoscopic versus Open stoma creation: A retrospective analysis.

OBJECTIVES: This study aimed to compare open stoma (OS) creation with laparoscopic stoma (LS) creation considering the operation time, blood loss, time of oral intake, and complications. We also compared multiport LS and single-incision laparoscopic stoma (SILS) creation. METHODS: We reviewed the demographic data, diagnosis, indications, operation time, blood loss, time of oral intake, operative procedure, and complications of 50 patients who underwent stoma creation between April 2014 and April 2016. RESULTS: The mean blood loss was significantly lower in the LS group (7.85±18.4 ml) than in the OS group (38.1±73.2 ml; P=0.02). There were no statistical differences between the groups in terms of the operation time (LS, 72.1±32.7 min; OS, 61.2±31.2 min; P=0.23) or time of oral intake (LS, 1.0±0 days; OS, 1.91±2.71 days; P=0.17). Peristomal skin problems occurred in 11 patients (47.8%) in the OS group and 5 patients (18.5%) in the LS group. There were no statistically significant differences between the SILS and multiport LS groups, considering the operation time, amount of bleeding, and time of oral intake. CONCLUSIONS: LS is comparable with OS in terms of operation time and time of oral intake and may cause lesser blood loss. Considering its advantages, LS is a useful approach for patients requiring biopsies or intra-abdominal inspection. SILS is a minimally invasive technique, suitable for patients in whom the stoma site is preoperatively decided.

Laparoscopic total pelvic exenteration using transanal minimal invasive surgery technique with en bloc bilateral lymph node dissection for advanced rectal cancer.

A 59-year-old man presenting with fecal occult blood visited our hospital. He was diagnosed with advanced lower rectal cancer, which was contiguous with the prostate and the left seminal vesicle. There were no metastatic lesions with lymph nodes or other organs. We performed laparoscopic total pelvic exenteration (LTPE) using transanal minimal invasive surgery technique with bilateral en bloc lateral lymph node dissection for advanced primary rectal cancer after neoadjuvant chemoradiotherapy. The total operative time was 760 min, and the estimated blood loss was 200 ml. LTPE is not well established technically, but it has many advantages including good visibility of the surgical field, less blood loss, and smaller wounds. A laparoscopic approach may be an appropriate choice for treating locally advanced lower rectal cancer, which requires TPE.

Epigenome-wide association study suggests that SNPs in the promoter region of RETN influence plasma resistin level via effects on DNA methylation at neighbouring sites.

AIMS/HYPOTHESIS: To investigate epigenetic regulation of the plasma concentration of resistin, we performed an epigenome-wide association study for this variable and DNA methylation (DNAm) in an elderly Japanese cohort and then assessed the relation of single nucleotide polymorphisms (SNPs) associated with the plasma resistin concentration to DNAm level at identified sites. METHODS: The association of plasma resistin level with DNAm status was examined in 191 nondiabetic elderly men with the Illumina Infinium HumanMethylation450 BeadChip array. The association between DNAm status at specific sites in the flanking region of the resistin gene (RETN) and RETN mRNA abundance was then evaluated with a public data set for 1202 monocyte samples from a multi-ethnic cohort. Finally, the association of DNAm status and SNPs in the promoter region of RETN was assessed in two cohorts comprising a total of 478 Japanese individuals. RESULTS: DNAm status at cg02346997 located in the RETN promoter region showed a negative genome-wide significant association with the plasma resistin level (p = 6.02 × 10(-10)). Four DNAm sites in the RETN promoter region including cg02346997 (p = 4.23 × 10(-70)) showed a negative genome-wide significant association with RETN mRNA abundance in monocytes. Furthermore, the number of minor alleles of the RETN promoter SNPs rs34861192 and rs3219175 was negatively associated with DNAm level at cg02346997 (p = 4.43 × 10(-17)). CONCLUSIONS/INTERPRETATION: Our results suggest that RETN promoter SNPs might influence the circulating resistin level through an effect on DNAm at cg02346997 and on RETN mRNA abundance in monocytes.

A single-cell and feeder-free culture system for monkey embryonic stem cells.

Primate pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), hold great potential for research and application in regenerative medicine and drug discovery. To maximize primate PSC potential, a practical system is required for generating desired functional cells and reproducible differentiation techniques. Much progress regarding their culture systems has been reported to date; however, better methods would still be required for their practical use, particularly in industrial and clinical fields. Here we report a new single-cell and feeder-free culture system for primate PSCs, the key feature of which is an originally formulated serum-free medium containing FGF and activin. In this culture system, cynomolgus monkey ESCs can be passaged many times by single-cell dissociation with traditional trypsin treatment and can be propagated with a high proliferation rate as a monolayer without any feeder cells; further, typical PSC properties and genomic stability can be retained. In addition, it has been demonstrated that monkey ESCs maintained in the culture system can be used for various experiments such as in vitro differentiation and gene manipulation. Thus, compared with the conventional culture system, monkey ESCs grown in the aforementioned culture system can serve as a cell source with the following practical advantages: simple, stable, and easy cell maintenance; gene manipulation; cryopreservation; and desired differentiation. We propose that this culture system can serve as a reliable platform to prepare primate PSCs useful for future research and application.

Angiotensin-converting enzyme inhibition promotes coronary angiogenesis in the failing heart of Dahl salt-sensitive hypertensive rats.

BACKGROUND: The biologic response to angiotensin-converting enzyme (ACE) inhibitors may be influenced by the local environment. The effect of ACE inhibition on coronary angiogenesis was investigated in a rat model of hypertensive heart failure. METHODS AND RESULTS: Dahl salt-sensitive (DS) rats fed a high-salt diet from 6 weeks of age were treated with a nonantihypertensive dose of the ACE inhibitor perindopril or vehicle from 9 to 18 weeks. Treatment of rats with perindopril attenuated the heart failure as well as cardiac hypertrophy and fibrosis that were manifest in the vehicle-treated animals. Myocardial capillary density as well as the expression of the bradykinin B(2) receptor, endothelial nitric oxide synthase, and vascular endothelial growth factor were reduced in the heart of vehicle-treated rats compared with that of nonhypertensive control rats, and all of these changes were attenuated by treatment with perindopril. CONCLUSIONS: These results indicate that ACE inhibition by perindopril promotes myocardial capillary formation as well as attenuates cardiac remodeling and failure in a manner independent from the antihypertensive effect of the drug in DS hypertensive rats. The beneficial cardiac effects of perindopril were associated with activation of the bradykinin-nitric oxide pathway in the heart.

[Real-time tissue elastography in chronic liver disease].

BACKGROUND/AIM: In patients with chronic liver diseases, the histological classification of liver fibrosis is essential for predicting prognosis and selecting appropriate antiviral therapy. This study aimed to determine the usefulness of a new noninvasive method for the assessment of liver fibrosis by using real-time tissue elastography, which can be performed with conventional ultrasound probes. METHODS: Thirty-nine patients who had liver fibrosis and had undergone liver resection or liver biopsy were included in this study. The surgical specimens obtained were examined to determine the histological stage of liver fibrosis. The strain ratio of subcutaneous fat tissue to liver tissue was calculated. We examined the correlation between the strain ratio and the histological liver fibrosis stage, and compared the utility with various surrogate liver fibrosis markers. RESULTS: The strain ratio significantly differed with the stage of liver fibrosis, and they had significant correlation (Kruskal-Wallis test: p<0.0001; Spearman's rank correlation, p<0.0001, r=0.797). We identified 5.8 and 3.7 as the cutoff values of strain ratio for the diagnosis of cirrhosis and significant fibrosis. The sensitivity at these values was 92.9% and 81.9% respectively; the specificity, 96.0% and 88.9%; and the areas under the receiver operating characteristic curve (AUROCs), 0.977 and 0.913, respectively. The AUROC was superior to the other surrogate liver fibrosis markers tested. CONCLUSIONS: Real-time tissue elastography is a useful method for the diagnosis of significant fibrosis and cirrhosis in patients with chronic liver diseases.

Beneficial effects of growth hormone-releasing peptide on myocardial oxidative stress and left ventricular dysfunction in dilated cardiomyopathic hamsters.

BACKGROUND: Growth hormone-releasing peptide (GHRP) may act directly on the myocardium and improve left ventricular (LV) function, suggesting a potential new approach to the treatment of cardiomyopathic hearts. The present study tested the hypothesis that the beneficial cardiac effects of GHRP might include attenuation of myocardial oxidative stress. METHODS AND RESULTS: Dilated cardiomyopathic TO-2 hamsters were injected with GHRP-2 (1 mg/kg) or saline from 6 to 12 weeks of age. F1B hamsters served as controls. Untreated TO-2 hamsters progressively developed LV dilation, wall thinning, and systolic dysfunction between 6 and 12 weeks of age. Marked myocardial fibrosis was apparent in untreated hamsters at 12 weeks of age in comparison with F1B controls. The ratio of reduced to oxidized glutathione (GSH/GSSG) was decreased and the concentration of 4-hydroxynonenal (4-HNE) was increased in the hearts of untreated TO-2 hamsters. Treatment with GHRP-2 attenuated the progression of LV remodeling and dysfunction, as well as myocardial fibrosis, in TO-2 hamsters. GHRP-2 also inhibited both the decrease in the GSH/GSSG ratio and the increase in the concentration of 4-HNE in the hearts of TO-2 hamsters. CONCLUSIONS: GHRP-2 can suppress the increase in the level of myocardial oxidative stress, leading to attenuation of progressive LV remodeling and dysfunction in dilated cardiomyopathic hamsters. (Circ J 2010; 74: 163 - 170).

A simple risk score to predict in-hospital death of elderly patients with acute decompensated heart failure--hypoalbuminemia as an additional prognostic factor.

BACKGROUND: Risk stratification for elderly patients with acute decompensated heart failure (ADHF) may help clinicians to select the appropriate therapy and raise the quality of care. METHODS AND RESULTS: The present study enrolled 349 patients aged over 65 years who were hospitalized with ADHF from January 2004 to October 2008. Five independent prognostic factors were identified by multivariate logistic regression analysis, and each factor was assigned a number of points proportional to its regression coefficient: prior heart failure hospitalization (2 points), sodium or=35 mg/dl (2 points), albumin or=980 pg/ml (2 points); in particular, hypoalbuminemia was identified as the strongest prognostic factor. The patients were stratified into 3 groups: low risk (0-4 points), moderate risk (5-7 points), and high risk (8-11 points). The respective in-hospital mortality rates were 1.6%, 15.8%, and 42.1% (P<0.05). CONCLUSIONS: In addition to known prognostic factors, hypoalbuminemia may provide important information for elderly patients with ADHF. A simple risk score may help to stratify the risk of in-hospital mortality and contribute to better clinical management of these elderly patients.

Appropriate use of nasal continuous positive airway pressure decreases elevated C-reactive protein in patients with obstructive sleep apnea.

BACKGROUND: C-reactive protein (CRP) is an important risk factor for cardiovascular disease. Furthermore, it has been reported that levels of CRP are increased in patients with obstructive sleep apnea (OSA). The aim of this study was to examine the effects of long-term therapy with nasal continuous positive airway pressure (nCPAP) on CRP levels and to investigate whether compliance with nCPAP therapy more effectively attenuated markers of systemic inflammation in patients with OSA. METHODS AND RESULTS: Fifty-five patients (mean [+/- SEM] age, 55 +/- 2 years; 44 male patients, 11 female patients) with newly diagnosed moderate-to-severe OSA (apnea-hypopnea index > 20 events/h) were studied before and after 6 months of nCPAP treatment. There was a significant reduction in CRP levels after nCPAP therapy (before nCPAP therapy, 0.23 +/- 0.03 mg/dL; after nCPAP therapy, 0.17 +/- 0.02 mg/dL; p < 0.01). Additionally, we divided these patients into two groups based on adherence to nCPAP therapy. A group of patients using nCPAP > 4 h/d and > 5 d/wk were designated as the good compliance group. The decrease in CRP concentration was significant (before nCPAP therapy, 0.23 +/- 0.04 mg/dL; after nCPAP therapy, 0.16 +/- 0.03 mg/dL; p < 0.05) in the good compliance group but not in the poor compliance group (before nCPAP therapy, 0.24 +/- 0.05 mg/dL; after nCPAP therapy, 0.20 +/- 0.05 mg/dL; p = 0.21). Furthermore, we divided those patients into a high CRP group (>/= 0.2 mg/dL) and a normal CRP group (< 0.2 mg/dL) before nCPAP therapy. The significant decrease in CRP levels in the good compliance group was evident only in those patients with an initially elevated CRP level (before nCPAP therapy, 0.48 +/- 0.08 mg/dL; after nCPAP therapy, 0.29 +/- 0.06 mg/dL; p < 0.05). CONCLUSION: Appropriate use of nCPAP in patients with OSA may be required to decrease elevated CRP levels, with possible implications for cardiovascular morbidity and mortality.