Anethum graveolens Linn. (dill) extract enhances the mounting frequency and level of testicular tyrosine protein phosphorylation in rats

Objective:To investigate the effect of Anethum graveolens(AG) extracts on the mounting frequency,histology of testis and epididymis,and sperm physiology.Methods:Male rats induced by cold immobilization before treating with vehicle or AG extracts [50,150,and 450 mg/kg body weight(BW)] via gastric tube for consecutive 1,7,and 14 d were examined for mounting frequency,testicular phosphorylation level by immunoblotting,sperm concentration,sperm acrosome reaction,and histological structures of testis and epididymis,respectively.Results:AG(50 mg/kg BW) significantly increased the mounting frequency on Days 1 and 7 compared to the control group.Additionally,rat testis treated with 50 mg/kg BW AG showed high levels of phosphorylated proteins as compared with the control group.In histological analyses,AG extract did not affect the sperm concentration,acrosome reaction,and histological structures of testis and epididymis.Conclusions:AG extract enhances the aphrodisiac activity and is not harmful to sperm and male reproductive organs.     

Should few retrieved oocytes be as an indication for intracytoplasmic sperm injection?

Objective

To reevaluate whether relatively few oocytes obtained in one cycle are an indication for intracytoplasmic sperm injection (ICSI).

Methods

A total of 406 cycles with three or fewer retrieved oocytes performed in 396 non-male infertile couples were retrospectively reviewed. Cycles were classified into three groups by different fertilization techniques: the in vitro fertilization (IVF) group, insemination with conventional IVF; the ICSI group, insemination with ICSI though semen parameters were normal; and the rescue ICSI group, re-insemination with ICSI after conventional IVF failure.

Results

The ICSI group resulted in higher normal fertilization compared with the conventional IVF group. Correspondingly, the cycle cancellation rate was decreased in the ICSI group, though it was not statistically significant. The clinical pregnancy rate and implantation rate were lower in the ICSI group compared with the conventional IVF group. Rescue ICSI was a method to avert total fertilization failure in conventional IVF, increasing fertilization and ensuring embryo availability for transfer, but the normal fertilization was the lowest due to delayed insemination and the chance of pregnancy was very little.

Conclusions

Obtaining only few oocytes in one cycle is not considered as an indication for ICSI when the sperm sample is apparently normal. Rescue ICSI is either not recommended if conventional insemination fails. Such patients should not be subjected to the unnecessary costs and potential risks of ICSI.     

Methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

Objective:The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase(MTHFR) C677T excision repair cross-complementation group 1(ERCC1) genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer(NSCLC).Methods:A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regimens.The polymorphisms of MTHFR C677T,ERCC1 C8092A,and ERCC1 C118T were genotyped using the TaqMan methods.Results:The overall response rate was 28.9%.Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype(TT or CT)(41.2% versus 19.1%,P=0.01).Median time to progression(TTP) of patients with MTHFR CC genotype was longer than that of patients with variant genotype(7.6 months versus 5.0 months,P=0.003).No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival.Conclusions:Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.     

β-receptor blocker influences return of spontaneous circulation and chemical examination in rats during cardiopulmonary resuscitation

Objective

We investigated the influence of β-receptor blocker metoprolol on return of spontaneous circulation (ROSC) during cardiopulmonary resuscitation (CPR) in rats with induced myocardial infarction (MI).

Methods

Male Sprague-Dawley rats were randomly divided into three groups: the sham-operated group, the MI group without metoprolol, which was fed the vehicle, and the MI+metoprolol group receiving intragastric metoprolol. Each group was further divided randomly into three subgroups, depending on the dosage of epinephrine administered during subsequent CPR applied after the induction of asphyxial cardiac arrest.

Results

The ROSC rate was significantly decreased in the low dose subgroup of MI group, unchanged in the medium dose subgroup of MI group, and significantly decreased in the high dose subgroup of MI group, compared with the same dose subgroup of sham-operated group. MI+metoprolol group had a lower ROSC rate than MI group in the medium dose subgroup, and a higher ROSC rate than MI group in the high dose subgroup. There was no difference in blood K⁺ values of successful rats between MI group and MI+metoprolol group. The rats with successful CPR had lower blood K⁺ values than rats with unsuccessful CPR in each of the three treatment groups.

Conclusions

Metoprolol administered to MI rats over a long period significantly improved ROSC rates under an appropriate dose of epinephrine during CPR. An increasing high blood K⁺ value would attenuate the rate of a successful CPR.     

Tissue-engineered composite scaffold of poly(lactide-<Emphasis Type="Italic">co</Emphasis>-glycolide) and hydroxyapatite nanoparticles seeded with autologous mesenchymal stem cells for bone regeneration

Objective

A new therapeutic strategy using nanocomposite scaffolds of grafted hydroxyapatite (g-HA)/poly(lactide-co-glycolide) (PLGA) carried with autologous mesenchymal stem cells (MSCs) and bone morphogenetic protein-2 (BMP-2) was assessed for the therapy of critical bone defects. At the same time, tissue response and in vivo mineralization of tissue-engineered implants were investigated.

Methods

A composite scaffold of PLGA and g-HA was fabricated by the solvent casting and particulate-leaching method. The tissue-engineered implants were prepared by seeding the scaffolds with autologous bone marrow MSCs in vitro. Then, mineralization and osteogenesis were observed by intramuscular implantation, as well as the repair of the critical radius defects in rabbits.

Results

After eight weeks post-surgery, scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) revealed that g-HA/PLGA had a better interface of tissue response and higher mineralization than PLGA. Apatite particles were formed and varied both in macropores and micropores of g-HA/PLGA. Computer radiographs and histological analysis revealed that there were more and more quickly formed new bone formations and better fusion in the bone defect areas of g-HA/PLGA at 2–8 weeks post-surgery. Typical bone synostosis between the implant and bone tissue was found in g-HA/PLGA, while only fibrous tissues formed in PLGA.

Conclusions

The incorporation of g-HA mainly improved mineralization and bone formation compared with PLGA. The application of MSCs can enhance bone formation and mineralization in PLGA scaffolds compared with cell-free scaffolds. Furthermore, it can accelerate the absorption of scaffolds compared with composite scaffolds.

     

A preliminary evaluation of VEGF-A,VEGFR1 and VEGFR2 in patients with well-controlled type 2 diabetes mellitus

Objective

Decompensated chronic hyperglycemia often leads to late microvascular complications such as retinopathy, diabetic foot syndrome, and diabetic kidney disease. The aim of this study was to determine the concentration of vascular endothelial growth factor A (VEGF-A) and its receptors in patients with well-controlled diabetes.

Methods

The study was conducted on 31 patients with well-controlled type 2 diabetes without micro-or macroangiopathy. Thirty healthy volunteers were enrolled in a control group. Serum concentrations of VEGF-A, VEGF receptors 1 and 2 (VEGFR1 and VEGFR2), fasting glucose, and lipid profiles were measured, and the plasma concentration of glycated hemoglobin (HbA1c) was determined.

Results

No significant differences were observed between the concentration of VEGF-A, VEGFR1 or VEGFR2 in the subject group and that in the control group. Positive correlations were noted between the levels of VEGF-A, VEGFR2, and triglyceride, and there was a negative correlation between the levels of VEGFR2 and high-density lipoprotein (HDL)-cholesterol in the study group.

Conclusions

The concentrations of VEGF-A and its receptors 1 and 2 in patients with well-controlled diabetes are comparable to those of healthy individuals, which may indicate that appropriate control of glucose levels delays the occurrence of vascular complications. A negative correlation between VEGFR2 and HDL-cholesterol levels, and positive correlations between VEGF-A, VEGFR2, and triglyceride levels, suggest that lipid abnormalities occurring in diabetes may be involved in the modulation of angiogenesis.     

Delivering MC3T3-E1 cells into injectable calcium phosphate cement through alginate-chitosan microcapsules for bone tissue engineering

研究目的：本研究应用海藻酸钠-壳聚糖微囊保护成骨细胞,接种到β-磷酸三钙/磷酸钙骨水泥（β-TCP/CPC）浆料中,使β-TCP/CPC骨修复材料具有一定的细胞活性,同时提高固化后材料的孔隙率和孔径,以最终实现提高β-TCP/CPC骨水泥的降解速度,加快成骨和骨修复。创新要点：本研究首次应用海藻酸钠-壳聚糖微胶囊包封成骨细胞与CPC浆料复合,复合后实现自动细胞释放,释放出的细胞具有良好的生物学活性。研究方法：（1）高压静电成囊法制备载小鼠成骨前体细胞（MC3T3-E1）的海藻酸钙和海藻酸钠-壳聚糖微胶囊;（2）微囊化MC3T3-E1细胞,进行体外培养,使用细胞计数试剂盒（CCK-8）检测细胞活性,并用钙黄绿素-AM（Calcein-AM）和碘化丙啶（PI）进行活死细胞双重染色;（3）微囊化MC3T3-E1细胞与β-TCP/CPC浆料复合培养后,激光共聚焦扫描显微镜和环境扫描电子显微镜观测细胞在材料上的释放、粘附,CCK-8法检测材料上细胞的活力,碱性磷酸酶（ALP）检测观察细胞的分化状况,茜素红染色观察释放细胞的矿化能力。重要结论：海藻酸钠-壳聚糖微胶囊可作为可注射磷酸钙骨水泥内部接种成骨细胞并实现细胞释放的良好载体,释放出的成骨细胞具有良好的生物学活性。     

Effects of Huangqi and bear bile on recurrent parotitis in children: a new clinical approach

Objective:To evaluate the pharmacological effects of traditional Chinese medicine,bear bile capsule and Huangqi granule,on recurrent parotitis in children.Methods:In this prospective,controlled,and randomized study,a total of 151 young children were divided into three groups:Group A included massaging the children’s parotid region and melting vitamin C in their mouth daily;Group B included swallowing bear bile capsule and Huangqi granule daily;and Group C included massages and vitamin C as prescribed in Group A,and traditional Chinese medicine as prescribed in Group B.Children were treated individually for one month and then a follow-up study was conducted for 1 to 3.5 years.Analysis of variance(ANOVA) and Ridit analysis were employed for statistical analysis.Results:The recurrence rate decreased in every group,but was significantly more in Groups B and C when compared to Group A.The recurrences significantly decreased(P<0.01) in Group B and their recovery rate was as high as 63%,significantly better than those of the other groups(P<0.01).Conclusions:Huangqi and bear bile could be a novel clinical approach for treating recurrent parotitis in children.     

伴发ATTR型淀粉样沉积的骨关节炎患者的临床和生物学特征分析(英文)简

Objective： Our aim was to investigate clinical and laboratory characteristics of osteoarthritic patients who had amyloid deposition in their knee joints. Methods： Synovial membranes were obtained from 36 patients with knee osteoarthritis （OA） who underwent joint replacement surgery. From this sample, the diagnosis of amyloid was deter- mined by Congo red staining, which demonstrated apple-green birefringence under a polarized microscope. All syn- ovial membranes were immunohistochemically characterized for the expressions of amyloid immunoglobulin light chain （AL-K and AL-,k）, serum amyloid-A （SAA）, amyloidogenic transthyretin （ATTR）, and amyloidogenic 152- microglobulin （A152M）. Matrix-assisted laser desorption-ionizaton/time of flight mass spectrometry （MALDI-TOF MS） was used to analyze transthyretin （TTR） isoforms in the serum of each patient. Results： Nine cases （25%） were found to be amyloid-positive. Immunohistochemicaliy, eight cases （88.9%） had ATTR deposition, and one sample （11.1%） was shown to be AL-K-positive. MALDI-TOF MS identified that the TTR in the serum of the patients was unmodified wild-type TTR, TTR-Cys-S-S-Cys, and TTR-Cys-S-S-CysGly. The age at surgery and the disease duration were sig- nificantly higher in the ATTR-positive group than in the ATTR-negative group. Knee score and function score were significantly lower in the ATTR-positive group than in the ATTR-negative group. Conclusions： Amyloid deposition in synovial membranes of OA patients was found to be ATTR and AL-K. TTR in the serum of the patients was unmodified wild-type TTR together with two isoforms. The high age at surgery, long disease duration, and a deteriorated knee function were associated with ATTR amyloid deposition in the osteoarthritic knee joints.     

Antioxidant activity and protective effect of Clitoria ternatea flower extract on testicular damage induced by ketoconazole in rats

Background

Ketoconazole (KET), an antifungal drug, has adverse effects on the male reproductive system. Pre-treatments with antioxidant plant against testicular damage induced by KET are required. The flowers of Clitoria ternatea (CT) are proven to have hepatoprotective potential. However, the protective effect on KET-induced testicular damage has not been reported.

Objective

To investigate the protective effect of CT flower extracts with antioxidant activity on male reproductive parameters including sperm concentration, serum testosterone level, histopathology of the testis, and testicular tyrosine phosphorylation levels in rats induced with KET.

Methods

The antioxidant activity of CT flower extracts was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Male rats were treated with CT flower extracts (10, 50, or 100 mg/kg BW) or distilled water via a gastric tube for 28 d (preventive period: Days 1–21) and induced by KET (100 mg/kg BW) via intraperitoneal injection for 7 d (induction period: Days 22–28). After the experiment, all animals were examined for the weights of the testis, epididymis plus vas deferens and seminal vesicle, serum testosterone levels, sperm concentration, histological structures and diameter of testis, and testicular tyrosine phosphorylation levels by immunoblotting.

Results

The CT flower extracts had capabilities for DPPH scavenging and high reducing power. At 100 mg/kg BW, the extract had no toxic effects on the male reproductive system. Significantly, in CT+KET groups, CT flower extracts (50 and 100 mg/kg BW) alleviated the reduction of reproductive organ weight parameters, testosterone levels, and sperm concentration. In addition, CT flower extracts gave protection from testicular damage in KET-induced rats. Moreover, in the CT100+KET group, CT flower extracts significantly enhanced the expression of a testicular 50-kDa tyrosine phosphorylated protein compared with that of other groups.

Conclusions

C. ternatea flower extracts possessing antioxidant activity are not harmful to the male reproductive system and can protect against testicular damage in KET-induced rats.     

肝功能对意识消失时咪达唑仑血浆浓度和脑电双频谱指数的影响(英文)

研究目的:探索不同肝功能指数对镇静药咪达唑仑的敏感性以及脑电双频谱指数(BIS)的预测意识消失的影响。创新要点:明确不同肝功能状态的患者对中枢抑制药的敏感性以及BIS预测意识消失概率发生的敏感性。指导临床医生根据患者的肝功能状态合理使用中枢抑制药以及正确利用BIS预测镇定深度。研究方法:选择意识消失作为研究终点,以50%患者意识消失时的咪唑安定的浓度以及BIS值作为观察指标。重要结论:终末期肝病患者对中枢镇静药咪唑安定更敏感,该类患者在BIS预测意识消失概率发生的敏感性存在差异。     

Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation

Objective

Mesenchymal stem cell (MSC) transplantation is a promising therapy for ischemic heart diseases. However, poor cell survival after transplantation greatly limits the therapeutic efficacy of MSCs. The purpose of this study was to investigate the protective effect of angiopoietin-1 (Ang1) preconditioning on MSC survival and subsequent heart function improvement after transplantation.

Methods

MSCs were cultured with or without 50 ng/ml Ang1 in complete medium for 24 h prior to experiments on cell survival and transplantation. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Hoechst staining were applied to evaluate MSC survival after serum deprivation in vitro, while cell survival in vivo was detected by terminal deoxynucleotidyl transferase biotin-dUPT nick end labeling (TUNEL) assay 24 and 72 h after transplantation. Heart function and infarct size were measured four weeks later by small animal echocardiography and Masson??s trichrome staining, respectively.

Results

Ang1 preconditioning induced Akt phosphorylation and increased expression of Bcl-2 and the ratio of Bcl-2/Bax. In comparison with non-preconditioned MSCs, Ang1-preconditioned cell survival was significantly increased while the apoptotic rate decreased in vitro. However, the PI3K/Akt pathway inhibitor, LY294002, abrogated the protective effect of Ang1 preconditioning. After transplantation, the Ang1-preconditioned-MSC group showed a lower death rate, smaller infarct size, and better heart functional recovery compared to the non-preconditioned-MSC group.

Conclusions

Ang1 preconditioning enhances MSC survival, contributing to further improvement of heart function.     

Levosimendan versus dobutamine in critically ill patients: a meta-analysis of randomized controlled trials

Objective

To evaluate the clinical efficacy of levosimendan versus dobutamine in critically ill patients requiring inotropic support.

Methods

Clinical trials were searched in PubMed, EMBASE, and the Cochrane Central Registry of Clinical Trials, as well as Web of Science. Studies were included if they compared levosimendan with dobutamine in critically ill patients requiring inotropic support, and provided at least one outcome of interest. Outcomes of interest included mortality, incidence of hypotension, supraventricular arrhythmias, and ventricular arrhythmias.

Results

Data from a total of 3 052 patients from 22 randomized controlled trials (RCTs) were included in the analysis. Overall analysis showed that the use of levosimendan was associated with a significant reduction in mortality (269 of 1 373 [19.6%] in the levosimendan group, versus 328 of 1 278 [25.7%] in the dobutamine group, risk ratio (RR)=0.81, 95% confidence interval (CI) 0.70-0.92, P for effect=0.002). Subgroup analysis indicated that the benefit from levosimendan could be found in the subpopulations of cardiac surgery, ischemic heart failure, and concomitant β-blocker therapy in comparison with dobutamine. There was no significant difference in the incidence of hypotension, supraventricular arrhythmias, or ventricular arrhythmias between the two drugs.

Conclusions

In contrast with dobutamine, levosimendan is associated with a significant improvement in mortality in critically ill patients requiring inotropic support. Patients having cardiac surgery, with ischemic heart failure, and receiving concomitant β-blocker therapy may benefit from levosimendan. More RCTs are required to address the questions about no positive outcomes in the subpopulation in a cardiology setting, and to confirm the advantages in long-term prognosis.     

Complex coronary lesions and rotational atherectomy: one hospital’s experience

Objective

To evaluate the safety and effectiveness of rotational atherectomy followed by drug eluting stent (DES) implantation in patients with complex coronary lesions.

Methods

From August 2006 to August 2012, 253 consecutive patients with 289 lesions and who underwent rotational atherectomy in our center were enrolled in this study.

Results

The overall procedure success rate was 98% with the cost of two (0.8%) coronary perforations, three (1.2%) dissections, five (2.0%) slow flows or no flows, three (1.2%) peri-procedure myocardial infarctions, and two (0.8%) in hospital deaths. During follow-up (mean three years), one (0.4%) patient died, two (0.8%) patients had acute myocardial infarction, 14 (5.5%) had restenosis, and target lesion revascularization occurred in eight patients (3.2%).

Conclusions

Rotational atherectomy followed by DES implantation is a safe and effective technique for patients with complex coronary lesions, especially calcified and non-dilatable lesions.     

Endostatin inhibits hypertrophic scarring in a rabbit ear model

Objective:The present study was designed to use an in vivo rabbit ear scar model to investigate the efficacy of systemic administration of endostatin in inhibiting scar formation.Methods:Eight male New Zealand white rabbits were randomly assigned to two groups.Scar model was established by making six full skin defect wounds in each ear.For the intervention group,intraperitoneal injection of endostatin was performed each day after the wound healed(about 15 d post wounding).For the control group,equal volume of saline was injected.Thickness of scars in each group was measured by sliding caliper and the scar microcirculatory perfusion was assessed by laser Doppler flowmetry on Days 15,21,28,and 35 post wounding.Rabbits were euthanatized and their scars were harvested for histological and proteomic analyses on Day 35 post wounding.Results:Macroscopically,scars of the control group were thicker than those of the intervention group.Significant differences between the two groups were observed on Days 21 and 35(p<0.05).Scar thickness,measured by scar elevation index(SEI) at Day 35 post wounding,was significantly reduced in the intervention group(1.09±0.19) compared with the controls(1.36±0.28).Microvessel density(MVD) observed in the intervention group(1.73±0.94) was significantly lower than that of the control group(5.63±1.78) on Day 35.The distribution of collagen fibers in scars treated with endostatin was relatively regular,while collagen fibers in untreated controls were thicker and showed disordered alignment.Western blot analysis showed that the expressions of type I collagen and Bcl-2 were depressed by injection of endostatin.Conclusions:Our results from the rabbit ear hypertrophic scar model indicate that systemic application of endostatin could inhibit local hypertrophic scar formation,possibly through reducing scar vascularization and angiogenesis.Our results indicated that endostatin may promote the apoptosis of endothelial cells and block their release of platelet-derived growth factor(PDGF) and fibroblast growth factor(FGF),thereby controlling collagen production by fibroblasts.Blood vessel-targeted treatment may be a promising strategy for scar therapy.     

Propolis modulates vitronectin, laminin, and heparan sulfate/heparin expression during experimental burn healing

Objective

This study was aimed at assessing the dynamics of vitronectin (VN), laminin (LN), and heparan sulfate/heparin (HS/HP) content changes during experimental burn healing.

Methods

VN, LN, and HS/HP were isolated and purified from normal and injured skin of domestic pigs, on the 3rd, 5th, 10th, 15th, and 21st days following thermal damage. The wounds were treated with apitherapeutic agent (propolis), silver sulfadiazine (SSD), physiological salt solution, and propolis vehicle. VN and LN were quantified using an immunoenzymatic assay and HS/HP was estimated by densitometric analysis.

Results

Propolis treatment stimulated significant increases in VN, LN, and HS/HP contents during the initial phase of study, followed by a reduction in the estimated extracellular matrix molecules. Similar patterns, although less extreme, were observed after treatment with SSD.

Conclusions

The beneficial effects of propolis on experimental wounds make it a potential apitherapeutic agent in topical burn management.     

Comparison of laparoscopic hepatectomy,percutaneous radiofrequency ablation and open hepatectomy in the treatment of small hepatocellular carcinoma

Objective

Three mainstream techniques—laparoscopic hepatectomy (LH), percutaneous radiofrequency ablation (pRFA), and open hepatectomy (OH)—were compared in this study, in terms of their efficacies in the treatment of small hepatocellular carcinoma (HCC).

Methods

A comparative study was performed within a total of 94 patients diagnosed with small HCC in our hospital from 2005 to 2010, who underwent LH (28), RFA (33), or OH (33). They had either a single tumor lesion of less than 5 cm or up to three nodules with diameters of less than 3 cm each. Outcomes were carefully evaluated throughout a 3-year follow-up interval and statistically interpreted.

Results

The pRFA group had a significantly lower disease-free survival rate compared with the two surgical groups (P=0.001) and significantly shorter overall survival (P=0.005), while the LH group and the OH group had no difference in survival results. For patients younger than 60 years old, surgical approaches offered a better long-term overall survival prognosis (P=0.008). There were no statistically significant differences among the three groups in overall survival for elderly patients (P=0.104).

Conclusions

Among patients with small HCC, LH may provide better curative effects than pRFA without increasing complication rates. pRFA leads to faster recurrence than surgical resections. LH has similar therapeutic effects to OH and causes less trauma. For patients younger than 60 years old, LH may be the best curative treatment. Elderly patients may choose either surgery or pRFA.

     

Influence of injection of Chinese botulinum toxin type A on the histomorphology and myosin heavy chain composition of rat gastrocnemius muscles

Background and objective

Botulinum toxin type A (BoNT/A) is a metalloprotease that blocks synaptic transmission via the cleavage of a synaptosomal-associated protein of 25 kDa (SNAP-25). It has gained widespread use as a treatment for cerebral palsy and skeletal muscle hypertrophy. In China, Chinese botulinum toxin type A (CBTX-A), a type of BoNT/A, is in widespread clinical use. However, the changes in the morphological and biochemical properties of treated muscles and in remote muscles from the CBTX-A injection site are relatively unknown. Therefore, we investigated the changes in histomorphology and myosin heavy chain (MyHC) isoform composition and distribution in rat gastrocnemius muscles after intramuscular injection of CBTX-A.

Methods

The weakness of the injected muscles was assessed periodically to identify their functional deficiency. Muscle slices were stained with hematoxylin-eosin (HE) and adenosine triphosphatase (ATPase). MyHC isoform composition was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) to uncover changes in morphological and biochemical properties.

Results

Our findings demonstrate that following injection of CBTX-A 5 U into rat gastrocnemius muscles, shifts in MyHC isoform composition emerged on the third day after injection and peaked in the fourth week. The composition remained distinctly different from that of the control group after the twelfth week. More specifically, there was a decrease in the proportion of the type IIb isoform and an increase in the proportions of type IIx, type IIa, and type I isoforms.

Conclusions

Data revealed that CBTX-A led to a shift in MyHC composition towards slower isoforms and that the MyHC composition remained far from normal six months after a single injection. However, no noticeable remote muscle weakness was induced.     

Non-pulmonary vein foci induced before and after pulmonary vein isolation in patients undergoing ablation therapy for paroxysmal atrial fibrillation: incidence and clinical outcome

Objective

To evaluate the incidence and clinical outcome of adenosine triphosphate (ATP) plus isoproterenol (ISP)-induced non-pulmonary vein (PV) foci before and after circumferential PV isolation (CPVI) during index ablation in patients with paroxysmal atrial fibrillation (PAF).

Methods

In 80 consecutive patients undergoing catheter ablation for drug-refractory, symptomatic PAF at our hospital from April 2010 to January 2011, atrial fibrillation (AF) was provoked with ATP (20 mg) and ISP (20 μg/min) administration before and after CPVI. The spontaneous initiation of AF was mapped and recorded.

Results

Before ablation, AF mostly originating from PVs (PV vs. non-PV, 36/70 vs. 3/70; P<0.01) was induced in 39 patients with sinus rhythm. CPVI significantly suppressed AF inducibility; however, more non-PV foci were provoked (post-CPVI vs. pre-CPVI, 13/76 vs. 3/70; P=0.016). Patients with pre- and post-CPVI induced AF (n=49) were divided according to non-PV foci being induced (group N, n=17) or not (group P, n=32). After mean (19.2±8.2) months follow-up, 88.2% (15/17) and 65.6% (21/32) of patients in groups N and P, respectively, were free from AF recurrence (P=0.088).

Conclusions

ATP+ISP administration effectively provokes non-PV foci, especially after CPVI in PAF patients. Although in this study difference did not achieve statistical significance, supplementary ablation targeting non-PV foci might benefit clinical outcome.     

Reducing the oxidative stress mediates the cardioprotection of bicyclol against ischemia-reperfusion injury in rats

Objective

To investigate the beneficial effect of bicyclol on rat hearts subjected to ischemia-reperfusion (IR) injuries and its possible mechanism.

Methods

Male Sprague-Dawley rats were intragastrically administered with bicyclol (25, 50 or 100 mg/(kg·d)) for 3 d. Myocardial IR was produced by occlusion of the coronary artery for 1 h and reperfusion for 3 h. Left ventricular hemodynamics was continuously monitored. At the end of reperfusion, myocardial infarct was measured by 2,3,5-triphenyltetrazolium chloride (TTC) staining, and serum lactate dehydrogenase (LDH) level and myocardial superoxide dismutase (SOD) activity were determined by spectrophotometry. Isolated ventricular myocytes from adult rats were exposed to 60 min anoxia and 30 min reoxygenation to simulate IR injuries. After reperfusion, cell viability was determined with trypan blue; reactive oxygen species (ROS) and mitochondrial membrane potential of the cardiomyocytes were measured with the fluorescent probe. The mitochondrial permeability transition pore (mPTP) opening induced by Ca²⁺ (200 μmol/L) was measured with the absorbance at 520 nm in the isolated myocardial mitochondria.

Results

Low dose of bicyclol (25 mg/(kg·d)) had no significant improving effect on all cardiac parameters, whereas pretreatment with high bicyclol markedly reduced the myocardial infarct and improved the left ventricular contractility in the myocardium exposed to IR (P<0.05). Medium dose of bicyclol (50 mg/(kg·d)) markedly improved the myocardial contractility, left ventricular myocyte viability, and SOD activity, as well decreased infarct size, serum LDH level, ROS production, and mitochondrial membrane potential in rat myocardium exposed to IR. The reduction of ventricular myocyte viability in IR group was inhibited by pretreatment with 50 and 100 mg/(kg·d) bicyclol (P<0.05 vs. IR), but not by 25 mg/(kg·d) bicyclol. The opening of mPTP evoked by Ca²⁺ was significantly inhibited by medium bicyclol.

Conclusions

Bicyclol exerts cardioprotection against IR injury, at least, via reducing oxidative stress and its subsequent mPTP opening.