Decreased hepatic glucose production in obese rats by dipeptidyl peptidase-IV inhibitor sitagliptin

Background  Dipeptidyl peptidase-IV (DPP-4) inhibitors are now used to improve postprandial glycemic control in type 2 diabetes. However, their effects on hepatic glucose production (HGP) in obesity are not clear. This study was designed to test the hypothesis that gluconeogenesis and HGP can be modulated by DPP-4 inhibitors in obesity.

Methods  Sprague Dawley male rats were divided into four groups, each on a different diet: general rat chow, n=10 (G); G+sitagliptin, n=10; high fat chow (obesity), n=10 (55% fat calories, HFO); HFO+sitagliptin, n=10. After 10 weeks, the rats were fasted overnight and glucose metabolism was determined using 3-³H-glucose and ¹⁴C-glycerol as tracers.

Results  Glycerol rate of appearance (P <0.00001), plasma glycerol (P <0.05) and free fatty acid (FFA) (P <0.05) concentrations, and HGP (P <0.05) were decreased in HFO+sitagliptin group compared with HFO group, but there was no significant difference between G and G+sitagliptin groups (P >0.05). Gluconeogenesis in HFO group was five times of that in G rats (P <0.01), but was significantly declined in HFO+sitagliptin group (P <0.0001).

Conclusions  Gluconeogenesis and HGP were inhibited by sitagliptin in high fat-induced obese rats due to decreased glycerol availability, which was a result of reduced glycerol release from adipose tissues. The finding suggests that sitagliptin is potentially useful for controlling fasting glucose in obesity, thereby delaying or preventing the development of diabetes.

     

Expectant management of heterotopic cesarean scar pregnancy

Background  Heterotopic cesarean scar pregnancy (HCSP) is a very rare but life-threatening entity and there is no optimal management strategy. Here we report a successfully managed case of HCSP with expectant treatment in a tertiary referral hospital.

Methods  A woman with HCSP after in vitro fertilization-embryo transfer opted for expectant treatment after five days of mild bleeding and ultrasound demonstrated cardiac activity disappearance of the scar pregnancy at 8⁺⁴ weeks of gestation.

Results  The patient had mild to moderate bleeding during close monitoring. Three days later, speculum examination revealed the gestational mass was partly protruding at the os of the cervix and it was removed with forceps without massive hemorrhage. A healthy male baby was delivered by cesarean section at gestational age of 36⁺⁴ weeks.

Conclusions  The expectant method might be an alternative option for a HCSP with loss of cardiac activity of the scar pregnancy, when applied under supportive management and with available emergency surgery facilities.

     

Clinical evaluation of remineralization potential of casein phosphopeptide amorphous calcium phosphate nanocomplexes for enamel decalcification in orthodontics

are the focus of intense research. The aim of this study was to evaluate the remineralizing effect of casein phosphopeptide amorphous calcium phosphate (CPP-ACP) nanocomplexes on enamel decalcification in orthodontics.

Methods  Twenty orthodontic patients with decalcified enamel lesions during fixed orthodontic therapy were recruited to this study as test group and twenty orthodontic patients with the similar condition as control group. GC Tooth Mousse, the main component of which is CPP-ACP, was used by each patient of test group every night after tooth-brushing for six months. For control group, each patient was asked to brush teeth with toothpaste containing 1100 parts per million (ppm) of fluoride twice a day. Standardized intraoral images were taken for all patients and the extent of enamel decalcification was evaluated before and after treatment over this study period. Measurements were statistically compared by t test.

Results  After using CPP-ACP for six months, the enamel decalcification index (EDI) of all patients had decreased; the mean EDI before using CPP-ACP was 0.191±0.025 and that after using CPP-ACP was 0.183±0.023, the difference was significant (t=5.169, P <0.01). For control group, the mean EDI before treatment was 0.188±0.037 and that after treatment was 0.187±0.046, the difference was not significant (t=1.711, P >0.05).

Conclusion  CPP-ACP can effectively improve the demineralized enamel lesions during orthodontic treatment, so it has some remineralization potential for enamel decalcification in orthodontics.

     

Folfox4 regimen administered through combined hepatic arterial and systemic infusion for treatment of colorectal cancer with unresectable liver metastases

Background  Hepatic arterial infusion chemotherapy for liver metastases is under evaluation because of the high target dose and low general toxicity. To investigate the efficacy and safety of a Folfox4 regimen administered through a combined hepatic arterial and systemic infusion for the first-line treatment of colorectal cancer (CRC) with unresectable liver metastases.

Methods  Twenty-seven CRC patients with unresectable hepatic metastases and no prior chemotherapy were enrolled into the study. They received a Folfox4 regimen; 1st day: HAI of oxaliplatin 85 mg/m² and L-folinic acid 200 mg/m², followed by a bolus hepatic arterial injection of 5-fluorouracil 400 mg/m², then continuous HAI of 5-FU 600 mg/m²; 2nd day: infusion of L-folinic acid 200 mg/m² i.v. followed by an intravenous bolus injection of 5-Fluorouracil 400 mg/m², then continuous infusion of 5-fluorouracil 600 mg/m² i.v. The patients received HAI during the odd cycles, and the intravenous administration of the same Folfox4 regimen during the even cycles.

Results  A total of 236 treatment cycles were given with a median of 10 cycles. The therapy generated the following results after six treatment cycles: complete response (CR) 1/27 (3.7%), partial response (PR) 17/27 (63.0%), stable disease (SD) 6/27 (22.2%), and progress disease (PD) 3/27 (11.1%). Five patients had hepatectomy. The serum levels of both carcinoembryonic antigen (CEA) and CA19-9 were significantly reduced (P<0.05). A median time to progression of 11 months and a median overall survival of 24 months were documented. The major adverse events included grade 1/2 nausea/vomiting, upper abdominal pain, peripheral neuropathy, and neutropenia/ thrombocytopenia.

Conclusions  The Folfox4 regimen administered through combined hepatic arterial and systemic infusions is efficacious and safe for the treatment of CRC with unresectable liver metastases, and it facilitates the control of local lesions.

     

Effect of combining different calcium concentration dialysate on calcium balance in peritoneal dialysis patients

Background  Calcium and phosphorus metabolic disturbance are common in dialysis patients and associated with increased morbidity and mortality. Therefore, maintaining the balance of calcium and phosphate metabolism and suitable intact parathyroid hormone (iPTH) level has become the focus of attention. We investigated the effects of different peritoneal dialysate calcium concentrations on calcium phosphate metabolism and iPTH in continuous ambulatory peritoneal dialysis (CAPD) patients.

Methods  Forty stable CAPD patients with normal serum calcium were followed for six months of treatment with 1.25 mmol/L calcium dialysate (DCa1.25, PD4, 22 patients) or a combination of 1.75 mmol/L calcium dialysate (DCa1.75, PD2) and PD4 (18 patients) twice a day respectively. Total serum calcium (after albumin correction), serum phosphorus, iPTH, alkaline phosphatase (ALP) and blood pressure were recorded before and 1, 3 and 6 months after treatment commenced.

Results  No significant difference was found in baseline serum calcium, phosphorus between the two patient groups, but the levels of iPTH were significantly different. No significant changes were found in the dosage of calcium carbonate and active vitamin D during 6 months. In the PD4 group, serum calcium level at the 1st, 3rd, 6th months were significantly lower than the baseline (P <0.05). There was no significant difference in serum phosphorus after 6 months treatment. iPTH was significantly higher (P <0.001) at the 1st, 3rd, and 6th months compared with the baseline. No differences were seen in ALP and blood pressure. In the PD4+PD2 group, no significant changes in serum calcium, phosphorus, iPTH, ALP and BP during the 6-month follow-up period.

Conclusions  Treatment with 1.25 mmol/L calcium dialysate for six months can decrease serum calcium, increase iPTH, without change in serum phosphorus, ALP, and BP. The combining of PD4 and PD2 can stabilize the serum calcium and avoid fluctuations in iPTH levels.

     

Characteristic gene expression profiles in the progression from normal gastric epithelial cells to moderate gastric epithelial dysplasia and to gastric cancer

Background  Gastric cancer ranks high among the most common causes of cancer-related death worldwide. This study was designed to explore key genes involved in the progression of normal gastric epithelial cells to moderate gastric epithelial dysplasia (mGED) and to gastric cancer.

Methods  Twelve pairs of mGED tissues, gastric cancer tissues, and normal gastric tissues were collected by gastroscopy. Total RNA was then extracted and purified. After the addition of fluorescent tags, hybridization was carried out on a Gene chip microarray slide. Significance analysis of microarrays was performed to determine significant differences in gene expression between the different tissue types.

Results  Microarray data analysis revealed totally 34 genes that were expressed differently: 18 highly expressed (fold change >2; P <0.01) and 16 down-regulated (fold change >2; P <0.01). Of the 34 genes, 24 belonged to several different functional categories such as structural molecule activity, extracellular regions, structural formation, cell death, biological adhesion, developmental processes, locomotion, and biological regulation that were associated with cancer. The remaining 10 genes were not involved in cancer research. Of these genes, the expression levels of Matrix metalloproteinase-12 (MMP12), Caspase-associated recruitment domain 14 (CARD14), and Chitinase 3-like 1 (CHI3L1) were confirmed by semi-quantitative RT-PCR. A two-way clustering algorithm divided the 36 samples into three categories and the overall correct classification efficiency was 80.6% (29/36). Almost all of these genes (31/34) showed constant changes in the process of normal gastric epithelial cells to mGED to gastric cancer.

Conclusions  The results of this study provided global gene expression profiles during the development and progression from normal gastric epithelial cells to mGED to gastric cancer. These data may provide new insights into the molecular pathology of gastric cancer which may be useful for the detection, diagnosis, and treatment.

     

Reconstruction of segmental bone defects in the rabbit ulna using periosteum encapsulated mesenchymal stem cells-loaded poly(lactic-co-glycolic acid) scaffolds

Background  Repair of large bone defects remains a challenge for clinicians. The present study investigated the ability of mesenchymal stem cells (MSCs) and/or periosteum-loaded poly(lactic-co-glycolic acid) (PLGA) to promote new bone formation within rabbit ulnar segmental bone defects.

Methods  Rabbit bone marrow-derived MSCs (passage 3) were seeded onto porous PLGA scaffolds. Forty segmental bone defects, each 15 mm in length, were created in the rabbit ulna, from which periosteum was obtained. Bone defects were treated with either PLGA alone (group A), PLGA + MSCs (group B), periosteum-wrapped PLGA (group C) or periosteum-wrapped PLGA/MSCs (group D). At 6 and 12 weeks post-surgery, samples were detected by gross observation, radiological examination (X-ray and micro-CT) and histological analyses.

Results  Group D, comprising both periosteum and MSCs, showed better bone quality, higher X-ray scores and a greater amount of bone volume compared with the other three groups at each time point (P <0.05). No significant differences in radiological scores and amount of bone volume were found between groups B and C (P >0.05), both of which were significantly higher than group A (P <0.05). 

Conclusions  Implanted MSCs combined with periosteum have a synergistic effect on segmental bone regeneration and that periosteum plays a critical role in the process. Fabrication of angiogenic and osteogenic cellular constructs or tissue-engineered periosteum will have broad applications in bone tissue engineering.

     

Tissue-engineered calcium phosphate cement in rabbit femoral condylar bone defects

Background  Calcium phosphate cement (CPC) is a favorable bone-graft substitute, with excellent biocompatibility and osteoconductivity. However, its reduced osteoinductive ability may limit the utility of CPC. To increase its osteoinductive potential, this study aimed to prepare tissue-engineered CPC and evaluate its use in the repair of bone defects. The fate of transplanted seed cells in vivo was observed at the same time.

Methods  Tissue-engineered CPC was prepared by seeding CPC with encapsulated bone mesenchymal stem cells (BMSCs) expressing recombinant human bone morphogenetic protein-2 (rhBMP-2) and green fluorescent protein (GFP). Tissue-engineered CPC and pure CPC were implanted into rabbit femoral condyle bone defects respectively. Twelve weeks later, radiographs, morphological observations, histomorphometrical evaluations, and in vivo tracing were performed.

Results  The radiographs revealed better absorption and faster new bone formation for tissue-engineered CPC than pure CPC. Morphological and histomorphometrical evaluations indicated that tissue-engineered CPC separated into numerous small blocks, with active absorption and reconstruction noted, whereas the residual CPC area was larger in the group treated with pure CPC. In the tissue-engineered CPC group, in vivo tracing revealed numerous cells expressing both GFP and rhBMP-2 that were distributed in the medullar cavity and on the surface of bony trabeculae.

Conclusion  Tissue-engineered CPC can effectively repair bone defects, with allogenic seeded cells able to grow and differentiate in vivo after transplantation.

     

Efficacy of local aspiration in the conservative treatment of live interstitial pregnancy coexisting with live intrauterine pregnancy after in vitro fertilization and embryo transfer

Background  Heterotopic pregnancy (HP) is defined as a pregnancy in which one or more embryos is viably implanted in the uterus while the other is implanted elsewhere as an ectopic pregnancy. The occurrence of HP rises dramatically with the increased use of assisted reproductive technology. HP of interstitial pregnancy is one special situation which needs more concern. Here we evaluate the efficacy of local aspiration and instillation of hyperosmolar glucose in the treatment of live interstitial pregnancy complicated with live intrauterine pregnancy after in vitro fertilization and embryo transfer.

Methods  Five female patients were diagnosed with live interstitial pregnancies complicated with intrauterine pregnancies. They were treated with transvaginal ultrasound-guided aspiration of interstitial pregnancy and instillation of hyperosmolar glucose at the Center for Reproductive Medicine of Peking University Third Hospital from January 1st, 2008 to May 30th, 2011.

Results  Gemmule embryos in all 5 cases were aspirated successfully and there was no abdominal hemorrhage, threatened abortion or infection in any of the cases. The sac of interstitial pregnancy continued to progress after aspiration and stopped growing between 11 to 20 weeks. By the 30th week of pregnancy, 80% of the interstitial masses had disappeared. Four cases have delivered and one is still in on-going pregnancy. All of the four cases underwent cesarean section and there were nothing special detected in the corner of the uterus.

Conclusion  Local aspiration and instillation of hyperosmolar glucose may be an effective way to treat live interstitial pregnancy when coexisting with a live intrauterine pregnancy.

     

Gliosis after traumatic brain injury in conditional ephrinB2-knockout mice

Background  In response to the injury of the central nervous system (CNS), the astrocytes upregulate the expression of glial fibrillary acidic protein (GFAP), which largely contributes to the reactive gliosis after brain injury. The regulatory mechanism of this process is still not clear. In this study, we aimed to compare the ephrin-B2 deficient mice with the wild type ones with regard to gliosis after traumatic brain injury.

Methods  We generated ephrin-B2 knockout mice specifically in CNS astrocytes. Twelve mice from this gene-knockout strain were randomly selected along with twelve mice from the wild type littermates. In both groups, a modified controlled cortical impact injury model was applied to create a closed traumatic brain injury. Twenty-eight days after the injury, Nissl staining and GFAP immunofluorescence staining were used to compare the brain atrophy and GFAP immunoreactivity between the two groups. All the data were analyzed by t-test for between-group comparison.

Results  We successfully set up the conditional ephrin-B2 knockout mice strain, which was confirmed by genotyping and ephrin-B2/GFAP double staining. These mice developed normally without apparent abnormality in general appearance. Twenty-eight days following brain injury, histopathology revealed by immunohistochemistry showed different degrees of cerebral injuries in both groups. Compared with wild-type group, the ephrin-B2 knockout group exhibited less brain atrophy ratio for the injured hemispheres (P=0.005) and hippocampus (P=0.027). Also the wild-type group demonstrated greater GFAP immunoreactivity increment within hippocampal regions (P=0.008).

Conclusions  The establishment of conditional ephrin-B2 knockout mice provides us with a new way to explore the role of ephrin-B2 in astrocytes. Our findings revealed less atrophy and GFAP immunoreactivity in the knockout mice strain after traumatic brain injury, which implied ephrin-B2 could be one of the promoters to upregulate gliosis following brain injury.

     

Effects of laser irradiation on Trichophyton rubrum growth and ultrastructure

Background  Trichophyton rubrum (T. rubrum) is the most common causative agent of dermatophytosis worldwide. In this study, we examined the effect of laser irradiation on the growth and morphology of T. rubrum.

Methods  Colonies of T. rubrum were isolated (one colony per plate), and randomly assigned to 5 treatment groups: Q-switched  694 nm ruby laser treatment, long-pulsed Nd:YAG 1064 nm laser treatment, intense pulsed light (IPL) treatment, 308 nm excimer laser treatment and the blank control group without treatment. Standardized photographs were obtained from grown-up fungal plates prior to treatment. Colonies were then exposed to various wavelengths and fluences of laser light. To compare the growth of colonies, they were re-photographed under identical conditions three and six days post-treatment. To investigate the morphology of T. rubrum, scanning electron microscope (SEM) and transmission electron microscope (TEM) images were obtained from specimens exposed to 24 hours of laser treatment.

Results  Growth of T. rubrum colonies was significantly inhibited following irradiation by 694 nm Q-switched and 1064 nm long-pulsed Nd:YAG lasers. Other treatments exerted little or no effect. Q-switched laser irradiation exerted a stronger growth inhibitory effect than long-pulsed Nd:YAG laser irradiation. Following treatment by the Q-switched ruby laser system, T. rubrum hyphae became shrunken and deflated, and SEM images revealed rough, fractured hyphal surfaces, punctured with small destructive holes. TEM images showed that the hyphae were degenerating, as evidenced by the irregular shape of hyphae, rough and loose cell wall, and obscure cytoplasmic texture. Initially high electron density structure was visible in the cell; later, low-density structure appeared as a result of cytoplasmic dissolution. In contrast, the blank control group showed no obvious changes in morphology.

Conclusion  The Q-switched 694 nm ruby laser treatment significantly inhibits the growth and changes the morphology of T. rubrum.

     

Autologous bone marrow stem cell transplantation in critical limb ischemia: a meta-analysis of randomized controlled trials

Background  Amputation-free survival (AFS) has been recommended as the gold standard for evaluating No-Option Critical Limb Ischemia (NO-CLI) therapy. Early-phase clinical trials suggest that autologous bone-marrow derived cells (BMCs) transplantation may have a positive effect on patients with NO-CLI, especially decreasing the incidence of amputation. However, the BMCs therapeutic efficacy remains controversial and whether BMCs therapy is suitable for all CLI patients is unclear.

Methods  We conducted a meta-analysis using data from randomized controlled trials (RCTs) by comparing autologous BMCs therapy with controls in patients with critical limb ischemia, and the primary endpoint is the incidence of amputation. Pubmed, EBSCO and the Cochrane Central Register of Controlled Trials (to approximately July 25, 2012) were searched.

Results  Seven RCTs with 373 patients were enrolled in the meta-analysis. Because serious disease was the main reason leading to amputation in one trial, six studies with 333 patients were finally included in the meta-analysis. Pooling the data of the final six studies, we found that BMCs therapy significantly decreased the incidence of amputation in patients with CLI (odds ratio (OR), 0.37; 95% confidence interval (CI), 0.22 to 0.62; P=0.0002), and the efficacy had not significantly declined within 6 months after BMCs were transplanted; OR, 0.33; 95% CI, 0.16 to 0.70; P=0.004 within 6 months and OR, 0.30; 95% CI, 0.11 to 0.79; P=0.01 within 3 months. The rate of AFS after BMCs therapy was significantly increased in patients with Rutherford class 5 CLI (OR 3.28; 95% CI, 1.12 to 9.65; P=0.03), while there was no significant improvement in patients with Rutherford class 4 (OR 0.35; 95% CI, 0.05 to 2.33; P=0.28) compared with controls. The BMCs therapy also improved ulcer healing (OR, 5.83; 95% CI, 2.37 to 14.29; P=0.0001).

Conclusions  Our analysis suggests that autologous BMCs therapy has a beneficial effect in decreasing the incidence of amputation and the efficacy does not decrease significantly within 6 months after BMCs transplantation. Patients with Rutherford class 5 are suitable for BMCs therapy, while the efficiency in patients with Rutherford 4 needs further evaluation.

     

Total endoscopic nephroureterectomy for native kidney ipsilateral to transplanted kidney

Background  From limited exposure with management of the native distal ureter ipsilateral to the transplanted kidney, we usually choose open nephroureterectomy (NU) or laparoscopic NU combined with an open approach in renal transplant (RTx) recipients. We herein describe our preliminary experience with total endoscopic NU with bladder cuff (BC) excision and evaluate its feasibility for RTx recipients.

Methods  From August 2008 to June 2011, eight RTx recipients underwent total endoscopic NU with BC excision for clinically presumed native upper urinary tract urothelial carcinoma (UUT-UC) ipsilateral to the transplanted kidney. Cystoscopic circumferential excision of the ipsilateral ureteral orifice with BC was followed by retroperitoneal laparoscopic NU using early ureteral ligation without primary BC closure. The intact specimen was removed through a 3-cm flank incision (an enlarged trocar site). Perioperative and pathological data and oncological outcomes were collected and analyzed.

Results  All endoscopic procedures were completed successfully without major complications and with open conversion. The mean estimated blood loss was 100 ml with no blood transfusion. The mean operating room time was 234.8 minutes, mean time to ambulation was 2.6 days, and mean hospital stay was 9.0 days. Pathological findings confirmed UUT-UC in seven recipients, two with bladder UC. During the mean 25.2-month follow-up, none of the recipients developed recurrence, while two developed contralateral UUT-UC after the first NU.

Conclusion  Total endoscopic NU with BC excision is technically feasible and safe for RTx recipients.

     

Long-pulse Nd:YAG 1064-nm laser treatment for onychomycosis

Background  Recent research shows that lasers can inhibit fungal growth and that Nd:YAG 1064-nm lasers can penetrate as deep as the lower nail plate. The aim of this study was to observe the effect of a long-pulse Nd:YAG 1064-nm laser on 154 nails of 33 patients with clinically and mycologically proven onychomycosis.

Methods  Thirty-three patients with 154 nails affected by onychomycosis were randomly assigned to two groups, with the 154 nails divided into three sub-groups (II degree, III degree, and IV degree) according to the Scoring Clinical Index of Onychomycosis. The 15 patients (78 nails) in group 1 were given eight sessions with a one-week interval, and the 18 patients (76 nails) in group 2 were given four sessions with a one-week interval.

Results  In group 1, the effective rates at 8 weeks, 16 weeks, and 24 weeks were 63%, 62%, and 51%, respectively, and the effective rates in group 2 were 68%, 67%, and 53% respectively. The treatment effect was not significantly different between any sub-group pair (P >0.05).

Conclusions  Long pulse Nd:YAG 1064-nm laser was effective for onychomycosis. It is a simple and effective method without significant complications or side effects and is expected to become an alternative or replacement therapy for onychomycosis.

     

Ibutilide decreases defibrillation threshold by the reduction of activation pattern complexity during ventricular fibrillation in canine hearts

Background  Ibutilide has been commonly used for pharmacologic cardioversion of atrial fibrillation and flutter in clinical settings. The objective of this study was to investigate the effects of ibutilide on the defibrillation threshold (DFT), restitution properties, dispersion of refractoriness and activation patterns during ventricular fibrillation (VF).

Methods  Ibutilide was administrated intravenously in six open-chest beagles. Before and after the drug administration, 20-second episodes of VF were electrically induced and recorded with a 10×10 unipolar electrode plaque sutured on the lateral epicardium of the left ventricle. DFT and VF activation patterns, including type of epicardial activation maps, VF cycle length (VF-CL), conduction velocity, wavelength (WL) and reentry incidence, were measured. Restitution properties and dispersion of refractoriness were estimated from activation recovery intervals (ARI) during pacing.

Results  Compared to baseline, ibutilide markedly decreased the DFT by 31% ((491±14) V vs. (337±59) V, P <0.01). The drug significantly reduced the maximal slope of the restitution curve (1.34±0.08 vs. 0.76±0.06, P <0.01) and its epicardial dispersion (0.36±0.09 vs. 0.21±0.06, coefficient of variation, P=0.03). The dispersion of refractoriness was enhanced at the pacing cycle length of 300 ms to 160 ms by ibutilide. The drug significantly increased the VF-CL ((96±19) ms vs. (112±20) ms, P <0.01) and the WL ((41±9) mm vs. (52±14) mm, P=0.02) during VF, and reduced the reentry incidence by 25% (0.08±0.02 vs. 0.06±0.02, P <0.01). In the epicardial activation maps, ibutilide significantly reduced the percentage of more complex activation maps during VF.

Conclusions  Intravenous ibutilide significantly decreased the DFT. It might be due to reduction of activation pattern complexity during VF.

     

Ibutilide decreases defibrillation threshold by the reduction of activation pattern complexity during ventricular fibrillation in canine hearts

Background  Ibutilide has been commonly used for pharmacologic cardioversion of atrial fibrillation and flutter in clinical settings The objective of this study was to investigate the effects of ibutilide on the defibrillation threshold (DFT), restitution properties, dispersion of refractoriness and activation patterns during ventricular fibrillation (VF).

Methods  Ibutilide was administrated intravenously in six open-chest beagles. Before and after the drug administration, 20-second episodes of VF were electrically induced and recorded with a 10×10 unipolar electrode plaque sutured on the lateral epicardium of the left ventricle. DFT and VF activation patterns, including type of epicardial activation maps, VF cycle length (VF-CL), conduction velocity, wavelength (WL) and reentry incidence, were measured. Restitution properties and dispersion of refractoriness were estimated from activation recovery intervals (ARI) during pacing.

Results  Compared to baseline, ibutilide markedly decreased the DFT by 31% ((491±14) V vs. (337±59) V, P<0.01). The drug significantly reduced the maximal slope of the restitution curve (1.34±0.08 vs. 0.76±0.06, P<0.01) and its epicardial dispersion (0.36±0.09 vs. 0.21±0.06, coefficient of variation, P=0.03). The dispersion of refractoriness was enhanced at the pacing cycle length of 300 ms to 160 ms by ibutilide. The drug significantly increased the VF-CL ((96±19) ms vs. (112±20) ms, P<0.01) and the WL ((41±9) mm vs. (52±14) mm, P=0.02) during VF, and reduced the reentry incidence by 25% (0.08±0.02 vs. 0.06±0.02, P<0.01). In the epicardial activation maps, ibutilide significantly reduced the percentage of more complex activation maps during VF.

Conclusions  Intravenous ibutilide significantly decreased the DFT. It might be due to reduction of activation pattern complexity during VF.

     

Chronic intermittent hypoxia aggravates cardiomyocyte apoptosis in rat ovariectomized model

Background  The prevalence of obstructive sleep apnea (OSA) increases after menopause in women, but remains under diagnosed because of social or lifestyle factors. It is important to evaluate the hazards of OSA on cardiovascular disease in menopausal women. We tested the hypothesis that chronic intermittent hypoxia (CIH) may aggravate cardiomyocyte apoptosis in ovariectomized (OVX) Sprague Dawley (SD) rats; the changes of anti-oxidation ability in cardiac muscles may be one of the reasons for cardiomyocyte apoptosis.

Methods  Forty-eight 60-day old female SD rats were randomly divided into a CIH group, OVX group, OVX+CIH (OC) group, and handled control (HC) group, and the rats were exposed either to CIH (nadir O₂ 6%) or handled normoxic controls. The changes of body weight and whole heart weight were measured. Super oxide dismutase (SOD) and malonaldehyde (MDA) were used to evaluate the level of oxidative stress. TdT-mediated dUTP nick end labeling (TUNEL) was used to measure apoptosis in each rat. Western blotting was used to measure apoptosis associated proteins in cardiac muscle samples from each rat.

Results  When compared with the HC and CIH groups, the levels of oxidative stress in the OC and OVX groups were significantly higher. The levels of SOD in the HC, CIH, OC, and OVX groups were (47.99±4.89), (53.60±4.47), (20.99±2.72), and (30.64±3.79) mmol/mg protein; significantly increased in the CIH group (P <0.05) and significantly decreased in the OC (P <0.01) and OVX (P <0.05) groups. The levels of MDA in the HC, CIH, OVX, and OC groups were (1.63±0.20), (1.93±0.77), (3.30±0.39), and (1.95±0.20) mmol/mg protein; it significantly increased in the CIH (P <0.05), OC (P <0.01), and OVX (P <0.05) groups compared with the HC group. Bax protein expression was significantly increased and bcl-2 protein expression was significantly reduced after CIH compared with HC rats (P <0.05). The protein expression of bax and bcl-2 in the OC group was not significantly different from the CIH group, but the ratio of bax/bcl-2 was significantly increased in the OC group (P <0.05); this was associated with severe cardiomycyte apoptosis in the OC group. TUNEL confirmed this observation.

Conclusions  This study found that CIH may induce oxidative stress in OVX rats but not in CIH rats, and cause more severe cardiomyocyte apoptosis in OVX rats compared with CIH rats. This means that OVX rats exposed to CIH suffered more severe cardiac injury compared with CIH rats due to reduced antioxidation. These findings may partly explain the reason why OSA has a worse cardiovascular impact on menopausal women, and emphasize the importance of detection and early treatment of OSA in menopausal patients.

     

Effect of combination therapy with alginate dressing and mouse epidermal growth factor on epidermal stem cells in patients with refractory wounds

Background  The aim of this research was to determine the efficacy of combination therapy using an alginate dressing and mouse epidermal growth factor (mEGF) on proliferation and differentiation of epidermal stem cells (ESCs) in patients with refractory wounds.

Methods  Eighteen patients (12 males and 6 females, aged from 18 to 61 years (mean 36.4 years)) with various skin wounds, were treated by dressing changing for one month. The wounds were located in the foot (11), calf (3), thigh (2) and forearm (2). The patients were randomly divided into 3 groups: alginate dressing and mEGF (group A; n=6), mEGF (group B; n=6) and control (group C; n=6). Wound closure indexes were measured at 7, 14, 21 and 28 days. Samples were harvested for pathologic examination, at 7 and 14 days following treatment. Cytokeratin 10 (CK10) and cytokeratin 15 (CK15) positive cells were evaluated using the super-sensitivity (SP) immunohistochemical staining technique.

Results  Wound healing was promoted in groups A and B. In group A, the wound closure index was increased significantly (P <0.05), and in one case the maximum cure area reached 102 cm². Pathological examination identified a thicker epidermis, active angiogenesis and enhanced granulation in group A compared with groups B and C. Using the SP immunohistochemical staining technique, we showed that ESCs in group A were bigger in size and larger in number than in groups B and C. Overall, there was a significant difference in ESCs proliferation and differentiation between group A and group B (or C).

Conclusions  Combination therapy using an alginate dressing and mEGF shows increased proliferation and differentiation of ESCs in patients with refractory wounds compared with those treated with mEGF alone.

     

Endovascular recanalization of superior vena cava, brachiocephalic, and subclavian venous occlusions caused by nonmalignant lesions

Background  Endovascular recanalization (EVR) is becoming the primary therapy for patients with central venous (brachiocephalic, subclavian, and superior vena cava) occlusion (CVO) caused by benign etiology. In this study, we retrospectively analyzed our experience in using EVR to treat benign CVO in 10 patients between April 2005 and September 2010.

Methods  The mean age of the patients was 65.3 years, 2/10 cases were female, and the origin of cause of CVO in 7/10 cases was the hemodialysis access in the upper extremity. The patients were treated with primary stent placement and evaluated with immediate technical success rate and post-interventional patency rate after the procedure.

Results  Eight patients were treated successfully with stent placement and experienced symptomatic relief immediately. No technical complications were observed during EVR treatment. Patients were followed up by ultrasonography and venography. Median follow-up was 13 months. Three patients required secondary procedures to maintain patency.

Conclusions  EVR is an effective and safe treatment in patients with benign CVO. It provides immediate symptom relief and maintains a continuous access for hemodialysis.

     

Is the European System for Cardiac Operative Risk Evaluation useful in Chinese patients undergoing heart valve surgery?

Background  The European System for Cardiac Operative Risk Evaluation (EuroSCORE) is one of the most widely used risk models for the predicting mortality after cardiac surgery. The aim of this study was to validate the EuroSCORE model for predicting operative mortality in heart valve surgery on a Chinese multicenter database and comparing the performance of EuroSCORE with our new risk stratification system, the Sino System for Coronary Operative Risk Evaluation (SinoSCORE).

Methods  Data from patients undergoing heart valve surgery between January 2007 and December 2008 were retrospectively collected, from 43 hospitals in China. The EuroSCORE and the SinoSCORE were calculated for each patient. Mortality was defined as any in-hospital death. Area under the receiver operating characteristics curve (AUC) was used to study the discriminatory abilities of the models. The Hosmer-Lemeshow (H-L) goodness-of-fit test was used to study the calibration of the predictive models.

Results  A total of 15 367 patients were analyzed. For the entire cohort, the observed mortality was 2.34%, the predicted mortality was 3.71% (additive), 3.19% (logistic) and 3.66% (SinoSCORE). AUC was 0.747 for SinoSCORE, 0.699 additive and 0.696 for logistic EuroSCORE. Calibration of SinoSCORE and additive EuroSCORE was good (H-L: P=0.250 and P=0.051, respectively), but the logistic EuroSCORE model had a poor calibration (H-L: P<0.05). The discriminatory ability and calibration of the SinoSCORE were good in low- and high-risk patients. However, the discriminatory ability of the EuroSCORE model was poor in all risk deciles.

Conclusions  The EuroSCORE does not accurately predict mortality in Chinese patients with heart valve surgery, and the SinoSCORE is superior to the EuroSCORE at predicting in-hospital mortality in Chinese heart valve surgery patients.