Differences in the developmental origins of the periosteum may influence bone healing.

BACKGROUND AND OBJECTIVE: The jaw bone, unlike most other bones, is derived from neural crest stem cells, so we hypothesized that it may have different characteristics to bones from other parts of the body, especially in the nature of its periosteum. The periosteum exhibits osteogenic potential and has received considerable attention as a grafting material for the repair of bone and joint defects. MATERIAL AND METHODS: Gene expression profiles of jaw bone and periosteum were evaluated by DNA microarray and real-time polymerase chain reaction. Furthermore, we perforated an area 2 mm in diameter on mouse frontal and parietal bones. Bone regeneration of these calvarial defects was evaluated using microcomputed tomography and histological analysis. RESULTS: The DNA microarray data revealed close homology between the gene expression profiles within the ilium and femur. The gene expression of Wnt-1, SOX10, nestin, and musashi-1 were significantly higher in the jaw bone than in other locations. Microcomputed tomography and histological analysis revealed that the jaw bone had superior bone regenerative abilities than other bones. CONCLUSION: Jaw bone periosteum exhibits a unique gene expression profile that is associated with neural crest cells and has a positive influence on bone regeneration when used as a graft material to repair bone defects. A full investigation of the biological and mechanical properties of jaw bone as an alternative graft material for jaw reconstructive surgery is recommended.

Examination of the effect of changing to azilsartan from candesartan in renal transplant patients.

BACKGROUND: Azilsartan, an angiotensin receptor blocker (ARB), was administered to renal transplant recipients to investigate the safety and antihypertensive effect in addition to its ARB-characteristic organ-protective effect. METHODS: The subjects were 20 patients (18 males, 2 females; baseline serum creatinine 2.39 ± 1.33 mg/dL) responding poorly to candesartan, who suffered albuminuria (>0.3 g/g creatinine) and hypertension (>140/90 mm Hg) following renal transplantation. Three months after candesartan was switched to azilsartan 20 mg/d, blood pressure, creatinine-corrected urinary albumin excretion, urinary L-type acid binding protein, urinary 8-hydroxydeoxyguano-sine, serum creatinine, and estimated glomerular filtration rate were evaluated. Thirteen patients received cyclosporine (65.0%) and 7 received tacrolimus (35.0%). Another hypertensive (calcium antagonist) agent was combined in 7 (35.0%). RESULTS: Systolic blood pressure significantly decreased from 139.5 mm Hg (baseline) from 128.7 mm Hg (at 3 months), whereas no significant changes were observed for diastolic blood pressure. The percentage of patients achieving the target level of antihypertensive effect (blood pressure < 130/80 mm Hg) significantly improved from 30.0% (baseline) to 70.0% (at 3 months). No significant changes were observed in renal graft function, oxidative stress marker level, or biochemical examination findings. CONCLUSION: Sufficient antihypertensive effect was demonstrated soon after switching to azilsartan. However, no significant change was found in renal damage markers. Long-term study must be conducted to confirm the protective effect azilsartan on the transplanted kidney, as found with candesartan. The safety of azilsartan was demonstrated. If the transplanted kidney protection is demonstrated, this drug is expected to contribute to the improved long-term prognosis of renal transplant recipients.

Long-term renoprotective effect of candesartan in renal transplant patients.

BACKGROUND: The renoprotective effects of angiotensin II type 1 receptor blockers (ARBs) have been demonstrated in a number of clinical studies, but there are few evaluations of long-term ARB treatment. We measured blood pressure, urine protein, and estimated glomerular filtration rate (eGFR) among patients under long-term (up to 9 years) treatment with candesartan cilexetil to evaluate its safety and effectiveness to protect renal graft function. METHODS: This study of 41 patients (31 male and 10 female) who presented with proteinuria and hypertension (blood pressure >140/90 mm Hg) after receiving a renal graft. Their serum creatinine level at baseline was 1.51 ± 0.53 mg/dL. Cyclosporine or tacrolimus were concomitantly prescribed for 18 (43.9%) and 22 (53.7%) subjects, respectively. The ARB treatment period was ≥12 months (up to 9 years, mean 4.8 years). Combination with other antihypertensive drugs (calcium antagonists) was necessary in 14/41 subjects (34.1%). RESULTS: Significant declines in blood pressure were observed during the treatment period; blood pressure reduction target (blood pressure <130/80 mm Hg) was met in 56.1% for systolic and 68.3% for diastolic pressure. No significant increase in serum creatinine level or eGFR was observed. Urinary protein was reduced to negative or marginal in 63.4% of the subjects, demonstrating a significant decrease. CONCLUSIONS: Candesartan cilexetil was considered to be safe even for long-term treatment in renal transplant patients, and effective to protect renal graft function.

Laparoscopic donor nephrectomy: single-center experience.

OBJECTIVE: Laparoscopic living donor nephrectomy (LLDN) has become the standard procedure for renal transplantation. This technique is considered less invasive for the donor, allowing lower postoperative analgesic requirements and a faster return to daily activities. In Japan, 1123 renal transplantation were performed in 2009. And, almost 83% were living related procedures. The aim of this study was a retrospective assessment of the safety and outcomes of LLDN on renal transplantations. MATERIAL AND METHODS: We retrospectively analyzed the intraoperative data and surgical complications for 21 patients who underwent retroperitoneoscopic living donor nephrectomy between June 2009 and March 2011. RESULTS: LLDN was successfully completed in all patients, without conversion to open surgery. Mean operative time was 243.5 ± 46.0 minutes with an average blood loss of 46.0 ± 46.1 mL. Warm ischemic time was 2.1 ± 0.62 minutes. Hospital stay was 11.1 ± 2.7 days. There were no major donor complications. One patient presented a wound infection responding to conservative treatment. CONCLUSIONS: LLDN is a safe effective procedure. The vascular stapler is useful to manage the renal vessels.

Cytomegalovirus infection after prophylactic valganciclovir therapy post-kidney transplantation: case reports.

This report describes three patients who developed cytomegalovirus infection 4 months after high-risk donor+/recipient-(D+/R-) kidney transplantation, despite treatment with valgancyclovir (VGCV) for 3 months at low dose (450 mg/d).

Re-evaluation of stomach position as a simple prognostic factor in fetal left congenital diaphragmatic hernia: a multicenter survey in Japan.

OBJECTIVES: To document outcome and to explore prognostic factors in fetal left congenital diaphragmatic hernia (CDH). METHODS: This was a multicenter retrospective study of 109 patients with prenatally diagnosed isolated left CDH born between 2002 and 2007. The primary outcome was intact discharge, defined as discharge from hospital without major morbidities, such as a need for respiratory support including oxygen supplementation, tube feeding, parenteral nutrition or vasodilators. All patients were managed at perinatal centers with immediate resuscitation, gentle ventilation (mostly with high-frequency oscillatory ventilation) and surgery after stabilization. Prenatal data collected included liver and stomach position, lung-to-head ratio, gestational age at diagnosis and presence or absence of polyhydramnios. Stomach position was classified into four grades: Grade 0, abdominal; Grade 1, left thoracic; Grade 2, less than half of the stomach herniated into the right chest; and Grade 3, more than half of the stomach herniated into the right chest. RESULTS: Overall intact discharge and 90-day survival rates were 65.1% and 79.8%, respectively. Stomach herniation was classified as Grade 0 in 19.3% of cases, Grade 1 in 45.9%, Grade 2 in 13.8% and Grade 3 in 21.1%. Multivariate analysis revealed that liver position was the strongest prognostic variable for intact discharge, followed by stomach position. Based on our results, we divided patients into three groups according to liver (up vs. down) and stomach (Grade 0-2 vs. Grade 3) position. Intact discharge rates declined significantly from liver-down (Group I), to liver-up with stomach Grade 0-2 (Group II), to liver-up with stomach Grade 3 (Group III) (87.0%, 47.4% and 9.5% of cases, respectively). CONCLUSION: Current status and outcomes of prenatally diagnosed left CDH in Japan were surveyed. Stomach herniation into the right chest was not uncommon and its grade correlated with outcome. The combination of liver and stomach positions was useful to stratify patients into three groups (Group I-III) with different prognoses.

Superhydrophobic surfaces: are they really ice-repellent?

This work investigates the anti-ice performance of various superhydrophobic surfaces under different conditions. The adhesion strength of glaze ice (similar to that deposited during "freezing rain") is used as a measure of ice-releasing properties. The results show that the ice-repellent properties of the materials deteriorate during icing/deicing cycles, as surface asperities appear to be gradually damaged. It is also shown that the anti-icing efficiency of superhydrophobic surfaces is significantly lower in a humid atmosphere, as water condensation both on top of and between surface asperities takes place, leading to significantly larger values of ice adhesion strength. This work thus shows that superhydrophobic surfaces are not always ice-repellent and their use as anti-ice materials may therefore be limited.

Postoperative chylothorax in congenital diaphragmatic hernia.

INTRODUCTION: The mechanisms responsible for postoperative chylothorax in Congenital Diaphragmatic Hernia (CDH) patients remain unclear. The aim of the present study was to examine the clinical features of CDH that may contribute to an association with postoperative chylothorax. MATERIAL AND METHODS: 198 neonates with CDH, in whom surgical repair of a diaphragmatic defect was performed between 1981 and 2008, were retrospectively studied. The patients were divided into 2 groups; patients with postoperative chylothorax (group I, n=11) and patients without postoperative chylothorax (group II, n=187). The clinical findings were compared between group I and group II to investigate potential predictive parameters for an association with chylothorax. Moreover, the clinical findings and treatments were evaluated in patients with chylothorax. RESULTS: 11 of the 198 infants (5.5%) developed a chylothorax. Although the incidence of a prenatal diagnosis was slightly higher in group I, no relationship with other clinical features was found which would indicate the severity of CDH or the occurrence of postoperative chylothorax. Treatment for chylothorax was drainage alone in 2 cases, total parenteral nutrition with drainage in 8 infants and additional intrathoracic OK-432 infusion in 1 patient. No patients required surgical intervention for chylothorax. No recurrences were observed in this patient series. CONCLUSIONS: It was concluded that postoperative chylothorax is not rare in infants after CDH repair. However, no statistically significant predictive parameters for chylothorax were identified, except for the presence of a prenatal diagnosis.

Transcriptional induction of MMP-10 by TGF-beta, mediated by activation of MEF2A and downregulation of class IIa HDACs.

Transforming growth factor (TGF)-beta regulates the expression of matrix metalloproteinases (MMPs) and components of the extracellular matrix, thereby profoundly affecting the microenvironment of cells including cancerous ones. We studied MMP-10 induction by TGF-beta in mammary epithelial cells and found that the induction was dependent on the myocyte enhancer factor (MEF)-2 transcription factor. TGF-beta upregulated the gene promoter through the MEF2 site, and knockdown of the MEF2A transcription factor negatively affected MMP-10 induction, whereas its overexpression had a positive effect on the induction. In response to TGF-beta, acetylation and concomitant binding of MEF2A to the promoter region increased, thus suggesting a critical role of MEF2A in transactivation of MMP-10 by TGF-beta. Consistent with the fact that class IIa histone deacetylases (HDACs) interact with MEF2 and suppress transcription, knockdown of HDACs increased and their overexpression inhibited MMP-10 expression. Intriguingly, TGF-beta promoted proteasome-dependent degradation of HDACs. Consistent with this, acetylation of core histones was increased around the MEF2 site of the MMP-10 promoter by TGF-beta and alleviated by overexpression of HDACs. Collectively, it is possible that TGF-beta transcriptionally upregulated MMP-10 through activation of MEF2A, concomitant with acetylation of core histones increasing around the promoter, as a consequence of degradation of the class IIa HDACs.

By-side PCDD/Fs in technical PCB formulations of Kanechlor series.

The Japanese Kanechlor technical PCB formulations such as KC-300, KC-400, KC-500, KC-600 and KC-1000 have been examined for possible contamination with by-side PCDD/Fs. 75 PCDDs and 135 PCDF have been determined using isotope dilution, separation and enrichment on silica gel impregnated with activated carbon, and final HRGC/HRMS measurement. MonoCDDs to OCDD were absent in KC-300, KC-600 and KC-1000. Tetra- and PentaCDDs occurred at > 1 ng/g in KC-400 and KC-500. The Kanechlors were contaminated with nearly all 135 PCDFsw. In parallel with an increasing degree of chlorination of a particular Kanechlor formulation examined increased also the content of more chlorinated PCDFs. In term of total dioxin-like toxicity and TEQ loads the KC-500 contained highly toxic PCDD/Fs at 270 ng TEQ/g and followed by KC-400 with 269 ng TEQ/g, KC-600 with 188 ng TEQ/g, KC-1000 with 164 ng TEQ/g and KC-300 with 79 ng TEQ/g. From 99.5 to 100% of PCDD/Fs toxicity found in the Kanechlors was from PCDFs.

Efficacy of carvedilol for ischemia/reperfusion-induced oxidative renal injury in rats.

In renal transplantation, ischemia/reperfusion (I/R) injury is related to production of reactive oxygen species. In addition to its antihypertensive action due to nonselective beta-adrenergic blocking activity, carvedilol has potent antioxidant activity. This study was designed to investigate the effects of carvedilol on I/R injury in rats. On postoperative days 2 and 4, serum creatinine levels were higher among the control and the metoprolol treatment groups compared with the carvedilol treatment group (P < .005). However, there were no significant differences on postoperative day 7. In conclusion, increased antioxidant modulation by carvedilol attenuated renal I/R injury.

Arterial stiffness after successful renal transplantation.

Cardiovascular disease is a major barrier to the long-term survival of transplant recipients. The aim of this study was to determine whether successful renal transplantation improves the arterial stiffness resulting from chronic renal failure. This study involved a group of 9 recipients (23-56 years) who underwent successful renal transplantation at our clinic. The brachial-ankle pulse wave velocity and--intima-media thickness of the bilateral common carotid arteries were measured in each patient before and 1 year after successful renal transplantation. One year after renal transplantation, the 9 patients showed a mean serum creatinine level of 1.41 mg/dL. Assessment of arterial stiffness in this group revealed that the mean brachial-ankle pulse wave velocity was reduced after renal transplantation, but there was no reduction in the mean intima-media thickness of the bilateral common carotid arteries. There was a significant correlation between the variance ratios of pulse wave velocity and median blood pressure. The more effective blood pressure control provided by renal transplantation may functionally improve arterial stiffness. However, organic arterial stiffness remained unchanged 1 year after transplantation.

Extensive skin necrosis of the arm in a patient with complex regional pain syndrome.

We report a 36-year-old woman with complex regional pain syndrome (CRPS) type 1 presenting with extensive skin necrosis of the left arm. The patient cooled her arm with ice packs to ease severe pain due to CRPS, in spite of repeated cautions against frostbite injury. The regions of skin necrosis corresponded with the sites where she had applied ice packs. We considered that the severe skin necrosis in our case was due to a self-induced frostbite injury.

Characterization of Jumping translocation breakpoint (JTB) gene product isolated as a TGF-beta1-inducible clone involved in regulation of mitochondrial function, cell growth and cell death.

Jumping translocation breakpoint (JTB) is a gene located on human chromosome 1 at q21 that suffers an unbalanced translocation in various types of cancers, and potentially encodes a transmembrane protein of unknown function. The results of cancer profiling indicated that its expression was suppressed in many cancers from different organs, implying a role in the neoplastic transformation of cells. Recently, we isolated JTB as a TGF-beta1-inducible clone by differential screening. In this study, we characterized its product and biological functions. We found that it was processed at the N-terminus and located mostly in mitochondria. When expressed in cells, JTB-induced clustering of mitochondria around the nuclear periphery and swelling of each mitochondrion. In those mitochondria, membrane potential, as monitored with a JC-1 probe, was significantly reduced. Coinciding with these changes in mitochondria, JTB retarded the growth of the cells and conferred resistance to TGF-beta1-induced apoptosis. These activities were dependent on the N-terminal processing and induced by wild-type JTB but not by a mutant resistant to cleavage. These findings raised the possibility that aberration of JTB in structure or expression induced neoplastic changes in cells through dysfunction of mitochondria leading to deregulated cell growth and/or death.

HRGC/HRMS analysis of chloronaphthalenes in several batches of Halowax 1000, 1001, 1013, 1014 and 1099.

Chloronaphthalene (CN) congeners and homologue groups have been quantified in up to three batches of several types of technical CN formulations of the Halowax series (Halowax 1031, 1000, 1001, 1013, 1014 and 1099), to elucidate possible batch-to-batch compositional variations. Using isotope dilution and HRGC/HRMS a relatively large variation in CN congeners and homologues composition among the batches of particular types of the Halowax formulations could be noted, and also when compared to the composition declared by the manufacturer. Depending on the type of the Halowax formulation and its batch in total up to 54 peaks from chloronaphthalenes (Agilent Ultra 2 liquid phase), which represented 70 of 75 CN congeners theoretically possible, could be found in these mixtures. These congeners represented all CN homologue groups from mono- to octaCN but some co-eluted. A co-eluting congeners were such as: 1,4-/1,6- (nos. 5/7), 1,5-/2,7- (nos. 6/12), 2,6-1,7- (nos. 11/8) of diCNs; 1,3,6-/1,3,5- (nos. 20/19), 1,3,7-/1,4,6- (nos. 23/24), 1,6,7-/2,3,6- (nos. 25/26) of triCNs; 1,2,5,7-/1,2,4,6-/1,2,4,7- (nos. 37/33/34), 1,3,6,8-/1,2,5,6- (nos. 45/36), 1,2,3,5-/1,3,5,8- (nos. 28/43), 1,2,3,4-/1,2,3,7- (nos. 27/30), 1,2,5,8-/1,2,6,8- (nos. 38/40) of tetraCNs; 1,2,3,5,7-/1,2,4,6,7- (nos. 52/60), 1,2,3,5,8-/1,2,3,6,8- (nos. 53/55) of pentaCNs; 1,2,3,4,6,7-/1,2,3,5,6,7- (nos. 66/67), 1,2,3,4,5,7-/1,2,3,5,6,8- (64/68) and 1,2,4,5,6,8-/1,2,4,5,7,8- (nos. 71/72) of hexaCNs. Absent in the Halowaxes were CN congeners such as 1,3,8-triCN (no. 22) (<0.0002 mg/g), 1,3,6,7-tetraCN (no. 44), 1,2,3,6-TetraCN (no. 29), 1,2,3,6,7-pentaCN (no. 54) and 1,2,3,6,7,8-hexaCN (no. 70) (<0.0005 mg/g).

Chloronaphthalenes composition of several batches of Halowax 1051.

Halowax 1051 is the highest chlorinated technical chloronaphthalene mixture among seven known formulations of the Halowax series. Octa- and heptaCN homologue groups are the main CN constituents of Halowax 1051 with declared 90% and 10% contents, respectively. In this study, using an isotope dilution technique and HRGC/HRMS, octaCN and heptaCNs contents of six batches of Halowax 1051 were between 82-93% and 6.2-17%, respectively. Also mono- to hexaCNs were found in Halowax 1051, and their content more or less varied according to the batch; also, the abundance of a particular CN congeners varied. Tetra-, penta- and hexaCNs have been found in all six batches of Halowax 1051 examined, and their contents varied between 0.0024-0.77%, 0.031-0.22%, and 0.21-0.82%, respectively. TriCNs have been found in three of six batches, and mono- and diCNs in two of six batches with 0.0020-0.40, 0.0017-0.25 and 0.0012-0.34% for positive findings, respectively. 2,3-DiCN (no. 10), 1,8-diCN (no. 9) at < 0.0002 mg/g, 1,6,7-/2,3,6-triCNs (nos. 25/26), 1,3,8-triCN (no. 22) at < 0.0002 mg/g, 1,3,6,7-tetra (no. 44), 1,2,3,6-tetra- (no. 29), 1,2,7,8-tetraCN (no. 41) and 1,2,3,6,7,9-hexaCN (no. 70) at < 0.0005 mg/g have not been found in Halowax 1051.

By-side chlorodibenzo-P-dioxins and chlorodibenzofurans in technical chlorobiphenyl formulations of aroclor 1268, chlorofen, and clophen T 64.

Aroclor 1268, Chlorofen, and Clophen T 64 technical chlorobiphenyl formulations were examined for 75 congeners of chlorodibenzo-p-dioxin (CDD) and 135 congeners of chlorodibenzofuran (CDF) using isotope dilution technique, separation, and enrichment on silica gel impregnated with activated carbon and final high resolution gas chromatography (HRGC)/high resolution mass spectrometry (HRMS) quantification. Three the most highly chlorinated congeners of CDD were found in Aroclor 1268, Chlorofen, and Clophen T 64. In the case of CDF, the number of congeners identified was 108 with 44 coeluting in pairs and 3 in triplicate in Aroclor 1268, 16 with 4 coeluting in pairs in Chlorofen, and 88 with 46 coeluting in pairs and 3 in triplicate in Clophen T 64. The total CDD and CDF concentrations of Aroclor 1268, Chlorofen, and Clophen T 64 were 24, 160, and 8.5 ng/g and 1600,270,000, and 4000 ng/g, respectively. No mono- to hexa-CDDs could be quantified in Aroclor 1268 (<0.03 to <1 ng/g), Chlorofen (<0.07 to <0.3 ng/g), or Clophen T 64 (<0.007 to <2 ng/g), whereas two hepta-CDDs and octa-CDD were found in all three formulations, and Chlorofen was richer in those compounds, followed by Aroclor 1268 and Clophen T 64.