[Repeated stellate ganglion blockade for the treatment of ventricular tachycardia storm in patients with nonischemic cardiomyopathy: a new therapeutic option for patients with malignant arrhythmias].

Objectives: This study sought to describe our institutional experience of repeated percutaneous stellate ganglion blockade (R-SGB) as a treatment option for drug-refractory electrical storm in patients with nonischemic cardiomyopathy (NICM). Methods: This prospective observational study included 8 consecutive NICM patients who had drug-refractory electrical storm and underwent R-SGB between June 1, 2021 and January 31, 2022. Lidocaine (5 ml, 1%) was injected in the vicinity of the left stellate ganglion under the guidance of ultrasound, once per day for 7 days. Data including clinical characteristics, immediate and long-term outcomes, and procedure related complications were collected. Results: The mean age was (51.5±13.6) years. All patients were male. 5 patients were diagnosed as dilated cardiomyopathy, 2 patients as arrhythmogenic right ventricular cardiomyopathy and 1 patient as hypertrophic cardiomyopathy. The left ventricular ejection fraction was 37.8%±6.6%. After the treatment of R-SGB, 6 (75%) patients were free of electrical storm. 24 hours Holter monitoring showed significant reduction in ventricular tachycardia (VT) episodes from 43.0 (13.3, 276.3) to 1.0 (0.3, 34.0) on the first day following R-SGB (P<0.05) and 0.5 (0.0, 19.3) after whole R-SGB process (P<0.05). There were no procedure-related major complications. The mean follow-up was (4.8±1.1) months, and the median time of recurrent VT was 2 months. Conclusion: Minimally invasive R-SGB is a safe and effective method to treat electrical storm in patients with NICM.

[Clinical characteristics and long-term follow-up results of radiofrequency ablation for the treatment of ventricular tachycardia in patients with arrhythmogenic left ventricular cardiomyopathy].

Objective: To investigate the acute and long-term outcome of catheter ablation for the treatment of ventricular tachycardia (VT) in patients with arrhythmogenic left ventricular cardiomyopathy (ALVC). Methods: This retrospective, cross-sectional study enrolled ALVC patients undergoing radiofrequency ablation for the treatment of VT at the First Affiliated Hospital of Nanjing Medical University from January 2011 to December 2018 and collected their clinical characteristics and intraoperative electrophysiological examination. Patients were followed up every 6 months after radiofrequency ablation until August 2021. Echocardiographic results and VT recurrence post radiofrequency ablation were analysed. Results: Totally 12 patients were enrolled (mean age: (42±15) years, 11 males(11/12)). The mean of left ventricular end diastolic diameter (LVDd) and left ventricular ejection fraction (LVEF) were (51±5)mm and (65±5)%, respectively. Twelve VTs were induced in 10 patients during the electrophysiological study, and the mean tachycardia cycle length was (293±65) ms. Three-dimensional substrate mapping revealed the diseased area at endocardial site in one patient, at epicardial sites in the other 11 patients (involved endocardial sites in 2 cases) with the basal part near the mitral annulus being the predilection for the substrate (10/11). After the catheter ablation at the endocardial and epicardial sites respectively, the complete procedure endpoint was achieved in all patients (VT cannot be induced post ablation). The median follow-up time was 65 (25, 123) months. One patient was lost to follow-up, and the other 11 patients survived without VT. No significant cardiac function deterioration was detected by the echocardiographic examination ((51±5)mm vs. (52±5)mm, P>0.05 for LVDd, (65±5)% vs. (60±6)%, P>0.05 for LVEF) at the end of follow-up. Conclusion: After radiofrequency ablation, the complete procedure endpoint is achieved in ALVC patients, and the catheter ablation provides long-term ventricular tachycardia control during the long-term follow-up.

Neuroprotection of ulinastatin on transient cerebral ischemia via antioxidative mechanisms.

Ulinastatin [also called urinary trypsin inhibitor (UTI)] has beneficial effects on cerebral ischemic injury evoked by cardiac arrest (CA). However, the underlying mechanisms are unknown. The purpose of this report was to determine the involvement of antioxidative signal pathway of the hippocampus in effects of UTI in the process of neurological functions after transient cerebral ischemia. CA was induced by asphyxia followed by cardiopulmonary resuscitation in rats. Western blot analysis and ELISA were used to examine expression of Nrf2-antioxidant response element (ARE) and superoxide dismutases (SOD), and the levels of products of oxidative stress. In addition, the modified neurological severity score (mNSS) and spatial working memory performance were employed to assess neurological deficiencies in CA rats. Our results show that CA impaired Nrf2-ARE and SOD in the hippocampus CA1 region and amplified products of oxidative stress, namely 8-isoprostaglandin F2α (8-iso PGF2α) and 8-hydroxy-2’-deoxyguanosine (8-OHdG). Systemic administration of UTI largely restored Nrf2-ARE and SOD, and this also attenuated amplification of 8-iso PGF2α and 8-OHdG induced by cerebral ischemia and thereby alleviated neurological deficits with increasing survival of CA rats. Our data suggest that UTI improves Nrf2-ARE signals and inhibits products of oxidative stress in the hippocampus, which is linked to improvement of neurological deficiencies in transient cerebral ischemia. UTI plays a beneficial role in modulating cerebral ischemic injury via antioxidative mechanisms.

An anionic defensin from Plutella xylostella with potential activity against Bacillus thuringiensis.

Insect defensins, are cationic peptides that play an important role in immunity against microbial infection. In the present study, an anionic defensin from Plutella xylostella, (designated as PxDef) was first cloned and characterized. Amino acid sequence analysis showed that the mature peptide owned characteristic six-cysteine motifs with predicted isoelectric point of 5.57, indicating an anionic defensin. Quantitative real-time polymerase chain reaction analysis showed that PxDef was significantly induced in epidermis, fat body, midgut and hemocytes after injection of heat-inactivated Bacillus thuringiensis, while such an induction was delayed by the injection of live B. thuringiensis in the 4th instar larvae of P. xylostella. Knocking down the expression of nuclear transcription factor Dorsal in P. xylostella by RNA interference significantly decreased the mRNA level of PxDef, and increased the sensitivity of P. xylostella larvae to the infection by live B. thuringiensis. The purified recombinant mature peptide (PxDef) showed higher activity against Gram-positive bacteria, with the minimum inhibition concentrations of 1.6 and 2.6 µM against B. thuringiensis and Bacillus subtilis, respectively. To our knowledge, this is the first report about an anionic PxDef, which may play an important role in the immune system of P. xylostella against B. thuringiensis.

[Clinical effects of free anterolateral thigh perforator flap pedicled with descending genicular artery in repairing wounds after lower leg limb-sparing surgery].

Objective: To explore the clinical effects of free anterolateral thigh perforator flap pedicled with descending genicular artery in repairing wounds after lower leg limb-sparing surgery. Methods: A retrospective observational study was conducted. From January 2019 to June 2021, 12 patients with wounds after lower leg limb-sparing surgery who met the inclusion criteria were admitted to Suzhou Ruihua Orthopedic Hospital, including 6 males and 6 females, aged 17 to 74 years, with original wound area ranging from 17 cm×9 cm to 40 cm×15 cm. Five patients had infection in wounds. The wounds were all repaired by free anterolateral thigh perforator flap from contralateral thigh, with area of 18 cm×10 cm to 37 cm×9 cm. The artery of flap was anastomosed with the descending genicular artery, and the wounds in donor areas were sutured directly. Seven patients were transplanted with split-thickness skin grafts from the contralateral thigh to cover the remaining wounds that can not be covered by flap and the wounds in donor areas were covered with gauze. During the operation, the types of perforating branch carried by flap and the types of arteries and veins in recipient areas were recorded. The survival and occurrence of vascular crisis of flap, the survival of skin graft, the wound healing in donor and recipient areas, and the length of hospital stay after flap transplant surgery were recorded. During follow-up, the color and texture of flap, reinfection in lower leg, and fracture healing were recorded. At the last follow-up, the limb salvage function of patients was evaluated according to the functional evaluation criteria of Chen Zhongwei's amputated limb replantation. Results: The types of perforating branches carried by flaps were as follows: 6 cases of only carrying the descending branch of the lateral circumflex femoral artery, 3 cases of only carrying the oblique branch of the lateral circumflex femoral artery, and 3 cases of carrying the descending branch of the lateral circumflex femoral artery and oblique branch of the lateral circumflex femoral artery after internal pressurization anastomosis. The types of arteries in the recipient area of flap were as follows: one case of main trunk of the descending genicular artery, 8 cases of the saphenous branch of the descending genicular artery, and 3 cases of the articular branch of the descending genicular artery. The types of veins in the recipient area of flap were as follows: 8 cases of one accompanying vein of the descending genicular artery and one branch of the great saphenous vein, and 4 cases of two branches of the great saphenous vein. All the flaps survived without vascular crisis, and all the skin grafts also survived. The wounds in the donor and recipient areas were all healed. The length of hospital stay of patient after flap transplant surgery ranged from 13 to 79 days. During the follow-up of 6 to 23 months, the color and texture of flap were both good, with no infection in lower leg wound. Internal or external fixation were removed after fracture healing in 5 patients, and bone graft internal fixation was performed in 7 patients whose fractures were not healed after surgery and all the incisions healed without infection. At the last follow-up, the limb salvage effect of patients was evaluated as followings: excellent in 7 patients, good in 4 patients, and fair in one patient. Conclusions: Free anterolateral thigh flap pedicled with descending genicular artery can effectively repair the wounds after lower leg limb-sparing surgery and control infection with short length of hospital stay, while not increasing the risk of secondary injury of distal limb vessels. Thus, it can obtain satisfactory limb salvage effect which is worthy of clinical promotion.

Efficacy and safety of pharmacotherapy for smoking cessation among pregnant smokers: a meta-analysis.

BACKGROUND: The efficacy and safety of pharmacotherapy for smoking cessation among pregnant smokers has not yet been established. OBJECTIVE: To investigate the efficacy and safety of pharmacotherapy for smoking cessation among pregnant smokers. SEARCH STRATEGY: A search was made of PubMed, Embase and CENTRAL in June 2011. SELECTION CRITERIA: Randomised controlled trials (RCTs), quasi-RCTs and retrospective or prospective controlled studies were included. DATA COLLECTION AND ANALYSIS: The main analyses were designed to examine the efficacy of pharmacotherapy for smoking cessation among pregnant smokers based on the longest follow-up data available and from data obtained at the latest available time-point in pregnancy in each study. MAIN RESULTS: Of 74 articles identified from the databases, seven studies (five RCTs, one quasi-RCT and one prospective study) involving a total of 1386 pregnant smokers, 732 in the intervention groups and 654 in the control groups, were included in the final analyses. In a fixed-effects meta-analysis of all seven studies based on the longest follow-up data available, pharmacotherapy had a significant effect on smoking cessation (relative risk [RR] 1.80; 95% confidence interval [CI] 1.32-2.44). Subgroup meta-analysis by type of study design also showed similar findings for RCTs (RR 1.48; 95% CI 1.04-2.09) and other types of studies (RR 3.25; 95% CI 1.65-6.39). The abstinence rate at late pregnancy in the intervention ranged from 7 to 22.6% (mean abstinence rate 13.0%; 95% CI 10.9-15.2%). A few minor adverse effects and serious adverse effects were reported in several studies. AUTHOR'S CONCLUSIONS: This study indicates that there may be clinical evidence to support the use of pharmacotherapy for smoking cessation among pregnant smokers. Further RCTs are needed.

Vitamin or antioxidant intake (or serum level) and risk of cervical neoplasm: a meta-analysis.

BACKGROUND: Case-control studies have reported the preventive effect of vitamin or antioxidant intake on cervical neoplasms such as cervical intraepithelial neoplasia (CIN) and invasive cervical cancer. However, the findings are inconsistent. OBJECTIVE: To investigate quantitative effects of vitamin or antioxidant intake on cervical neoplasm using meta-analysis. SEARCH STRATEGY: We searched PubMed, EMBASE and the Cochrane Library in November 2008. All articles searched were independently reviewed and selected by two evaluators according to predetermined selection criteria. SELECTION CRITERIA: We included case-control studies reporting an association between vitamin or antioxidant intake (or serum level) and cervical neoplasm risk and reporting the adjusted odds ratios (OR) and 95% confidence intervals (CI), whenever possible. DATA COLLECTION AND ANALYSIS: After retrieval of data from selected articles, we performed a meta-analysis using both fixed-effects and random- effects models. MAIN RESULTS: Of 274 articles meeting our initial criteria, we included 22 case-control studies involving a total of 10,073 participants. In meta-analyses by type of vitamin or antioxidant, a significant preventive effect on cervical neoplasm was found in intakes of vitamin B12 (OR 0.35, 95% CI 0.19-0.63; n=2), vitamin C (OR 0.67, 95% CI 0.55-0.82; n=8), vitamin E (OR 0.56, 95% CI 0.35-0.88; n=10), and beta-carotene (OR 0.68, 95% CI 0.55-0.84; n=9). AUTHORS' CONCLUSIONS: The findings of this meta-analysis indicate that overall, there were preventive effects of vitamin or antioxidant intake on cervical neoplasms in case-control studies.

Pharmacokinetics and bioequivalence of single dose and multiple doses of immediate- and extended-release formulations of dexibuprofen in healthy Chinese subjects.

OBJECTIVE: To compare the pharmacokinetic (PK) profiles and bioequivalence of the extended-release (ER) and immediate-release (IR) formulations of dexibuprofen (DI) in healthy Chinese volunteers after single dose and multiple doses. MATERIALS: Zefen® (IR capsule, containing 150 mg DI, Suzhou No.4 Pharmaceutical Factory, Jiangsu, China) and ER capsule (containing 225 mg DI, Tianjin Zhongtian Pharmaceutical Co. Ltd., Tianjin, China). METHODS: This was an open, randomized, two-period crossover study. Eligible subjects were healthy male Chinese volunteers. 22 subjects were randomly assigned to receive a single 450 mg dose of the test or reference formulation on the first day. During the next 6 days, the test group received a multiple-dose of ER DI capsule (450 mg, b.i.d.) and the reference group took a multiple-dose of IR DI capsule (300 mg, t.i.d.), respectively. Multiple blood samples were collected, and plasma concentrations of DI were analyzed using high performance liquid chromatography (HPLC) system. After a 9-day washout period, the subjects were administered the alternate formulation. Bioequivalence was concluded if the 90% confidence interval (CI) for the ratio between test and reference was within accepted limits. Adverse events (AEs) were monitored and documented throughout the confinement in the clinic and washout phases of each study period. RESULTS: 21 subjects completed the single dose administration and 20 subjects were evaluable for the multiple doses PK parameters. Single-dose Mean AUC0-t and AUC0-inf for ER formulation were 116.14 ± 21.54 mg·h/l and 117.60 ± 22.27 mg·h/l, and for IR formulation, were 107.25 ± 23.48 mg·h/l and 108.18 ± 23.93 mg·h/l, with the 90% CI within the limits accepted for bioequivalence. Mean Cmax for ER and IR formulations were 22.30 ± 5.17 mg/l and 30.26 ± 13.54 mg/l, respectively. And median tmax for ER and IR formulations were 4.5 h and 2.0 h. The retard quotient (delta R) for ER product was 1.9 ± 0.93, which indicated an intermediate extended release effect. Multiple-dose Mean AUC0-24 for ER formulation was 217.93 ± 41.07 mg·h/l and for IR formulation was 199.33 ± 37.32 mg·h/l. Other PK parameters of ER and IR formulations were as follows: median tmax were 4.8 h and 2.0 h, Css-max were 20.21 ± 2.69 mg/l and 19.71 ± 3.46 mg/l, Css-min were 2.47 ± 0.99 mg/l and 2.48 ± 0.99 mg/l, Cav were 9.08 ± 1.71 mg/l and 8.31 ± 1.56 mg/l, respectively. CONCLUSIONS: This study found that in these subjects, the absorption rates of the two DI formulations were not bioequivalent, but at steady state, the daily exposure provided by less frequent DI ER dosing was not significantly different from the same daily dose with DI IR capsules, administered more frequently.

Effects of antioxidant supplements on cancer prevention: meta-analysis of randomized controlled trials.

BACKGROUND: This meta-analysis aimed to investigate the effect of antioxidant supplements on the primary and secondary prevention of cancer as reported by randomized controlled trials. METHODS: We searched Medline (PubMed), Excerpta Medica database, and the Cochrane Review in October 2007. RESULTS: Among 3327 articles searched, 31 articles on 22 randomized controlled trials, which included 161 045 total subjects, 88 610 in antioxidant supplement groups and 72 435 in placebo or no-intervention groups, were included in the final analyses. In a fixed-effects meta-analysis of all 22 trials, antioxidant supplements were found to have no preventive effect on cancer [relative risk (RR) 0.99; 95% confidence interval (CI) 0.96-1.03). Similar findings were observed in 12 studies on primary prevention trials (RR 1.00; 95% CI 0.97-1.04) and in nine studies on secondary prevention trials (RR 0.97; 95% CI 0.83-1.13). Further, subgroup analyses revealed no preventive effect on cancer according to type of antioxidant, type of cancer, or the methodological quality of the studies. On the other hand, the use of antioxidant supplements significantly increased the risk of bladder cancer (RR 1.52; 95% CI 1.06-2.17) in a subgroup meta-analysis of four trials. CONCLUSIONS: The meta-analysis of randomized controlled trials indicated that there is no clinical evidence to support an overall primary and secondary preventive effect of antioxidant supplements on cancer. The effects of antioxidant supplements on human health, particularly in relation to cancer, should not be overemphasized because the use of those might be harmful for some cancer.

The immunoglobulin G response to Malassezia pachydermatis extracts in atopic and non-atopic dogs.

IgG immunoreactivity to Malassezia pachydermatis was compared in atopic and non-atopic dogs. Malassezia pachydermatis proteins with a molecular weight of 98 kDa were recognized at a significantly higher frequency in the sera of atopic dogs. Most of the atopic dogs with Malassezia dermatitis had a greater IgG response than did normal dogs.

Genetic analysis of first-trimester miscarriages with a combination of cytogenetic karyotyping, microsatellite genotyping and arrayCGH.

Miscarriage is the spontaneous loss of an embryo or fetus before the 20th week of pregnancy. Most miscarriages occur before the end of the first trimester (<13 weeks). Although many risk factors relate to this occurrence, genetic factors play the most important role. Chromosomal abnormalities, including both numerical and structural anomalies, underlie the majority of miscarriages. In this study, we employed a comprehensive approach using cytogenetic karyotyping, polymerase chain reaction (PCR)-based genotyping, and microarray-based comparative genomic hybridization (arrayCGH) in combination to analyze chromosomal profiles of 115 first-trimester miscarriages of Chinese women. Seventy cases (61%) were found to have chromosomal anomalies, of which 90% were numerical and 10% were structural. Cytogenetic karyotyping identified 78.6% (55/70), PCR assays 2.9% (2 triploids), and arrayCGH 18.6% (13/70) of the anomalies. In this study, a microdeletion of 108 kb and four microduplications sizing from 300 to 1460 kb were observed. An advantage of using this combination approach is that microsatellite genotyping and arrayCGH can be accomplished in spite of culture failure and maternal cell contamination. In addition, arrayCGH can detect submicroscopic chromosomal anomalies and gene dosage alterations.

Soy intake and risk of endocrine-related gynaecological cancer: a meta-analysis.

BACKGROUND: Epidemiology studies have reported associations between soy intake and the risk of endocrine-related gynaecological cancers. However, to date there have been no quantitative meta-analyses reported regarding this topic. OBJECTIVES: We investigated the quantitative associations between soy food intake and the risk of endometrial cancer and ovarian cancer by a meta-analysis of case-control studies and cohort studies. SEARCH STRATEGY: We searched MEDLINE (PubMed), EMBASE and the Cochrane Library during October 2008 using common keywords related to soy intake and endometrial or ovarian cancer. Two evaluators independently reviewed and selected articles, based on predetermined selection criteria. SELECTION CRITERIA: Included studies met all of the following criteria: (1) a case-control study or cohort study (to date, no randomized controlled trials have been reported); (2) investigated the associations between 'soy or soy product intake' and 'endometrial cancer' or 'ovarian cancer'; (3) reported outcome measures with adjusted odds ratios (OR) or relative risks (RR) and 95% confidence intervals (CI). DATA COLLECTION AND ANALYSIS: We investigated the associations between the overall soy intake (highest versus lowest intake) and the risk of endocrine-related gynaecological cancers (endometrial or ovarian cancer) as the main analysis. We also performed subgroup analyses by type of cancer (endometrial or ovarian), type of study design (case-control or cohort) and type of soy intake (soy foods or soy constituents). MAIN RESULTS: Out of 477 articles that met our initial criteria, a total of seven epidemiology studies consisting of five case-control studies and two cohort studies were included in the final analyses. Compared with the lowest soy intake, the OR for the highest soy intake was 0.61 (95% CI, 0.53-0.72) of all endocrine-related cancers among seven studies; 0.70 for endometrial cancer (95% CI, 0.57-0.86) and 0.52 for ovarian cancer (95% CI, 0.42-0.66) in the fixed-effects meta-analyses. The subgroup analyses by study design showed similar findings among the case-control studies (OR, 0.62; 95% CI, 0.53-0.73) and the cohort studies (OR, 0.57; 95% CI, 0.36-0.90). AUTHOR'S CONCLUSIONS: The results of the current study showed protective effects of soy intake on the risk for endocrine-related gynaecological cancers. Additional larger prospective studies are now needed.

MiR-21 relieves rheumatoid arthritis in rats via targeting Wnt signaling pathway.

OBJECTIVE: To investigate the influence of micro ribonucleic acid (miR)-21 on rats with rheumatoid arthritis (RA) through the Wnt signaling pathway. MATERIALS AND METHODS: A total of 30 rats were divided into three groups: control group (healthy rats, n=10), model group (rat model of RA, n=10), and MiR group (rat model of RA injected with miR-21 lentivirus, n=10). The paw volume, arthritis indexes, and protein expression level in each group were analyzed by means of paw volume and arthritis index measurement, reverse transcription-polymerase chain reaction (RT-PCR) assay, and fluorescent Western blotting. RESULTS: The expression levels of inflammatory factors declined in MiR group compared with those in model group, while they were higher in model group than those in control group and MiR group (p<0.05). At 15 d after transfection with lentivirus, the paw volume in MiR group was smaller than that in model group, which was decreased markedly with the extended time of transfection (p<0.05). On the 30th d, MiR group had a remarkably smaller paw volume than model group. In comparison with that in control group, the paw volume in model group was increased notably from the 7th d and displayed a significant difference in the 30th d (p<0.05). The arthritis indexes in MiR group were lower than those in model group; however, there were no apparent inflammations at the joints at 15 d after drug administration. Moreover, the longer the time of drug administration was, the less apparent the inflammations at the joints will be. The inflammations at the joints were ameliorated evidently on the 30th d in MiR group (p<0.05). Compared with those in control group, the inflammations in model group were increased significantly from the 7th d, with significant differences in the 30th d (p<0.05). The messenger RNA (mRNA) expression levels of interleukin-6 (IL-6), IL-8, and Wnt in MiR group were higher than those in control group, but lower than those in model group (p<0.05), while they were higher in model group than those in control group (p<0.05). The expression level of Wnt protein was decreased in MiR group compared with that in model group (p<0.05), and model group had a prominently elevated expression level of Wnt protein in comparison with control group (p<0.05). CONCLUSIONS: MiR-21 overexpression can repress the expressions of IL-6 and IL-8 and relieve the symptoms of RA by down-regulating the Wnt signal.

Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons.

Long-term potentiation (LTP) of excitatory transmission in the hippocampus likely contributes to learning and memory. The mechanisms underlying LTP at these synapses are not well understood, although phosphorylation and redistribution of AMPA receptors may be responsible for this form of synaptic plasticity. We show here that miniature excitatory postsynaptic currents (mEPSCs) in cultured hippocampal neurons reliably demonstrate LTP when postsynaptic NMDA receptors are briefly stimulated with glycine. LTP of these synapses is accompanied by a rapid insertion of native AMPA receptors and by increased clustering of AMPA receptors at the surface of dendritic membranes. Both LTP and glycine-facilitated AMPA receptor insertion are blocked by intracellular tetanus toxin (TeTx), providing evidence that AMPA receptors are inserted into excitatory synapses via a SNARE-dependent exocytosis during LTP.

Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization.

Redistribution of postsynaptic AMPA- (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-) subtype glutamate receptors may regulate synaptic strength at glutamatergic synapses, but the mediation of the redistribution is poorly understood. We show that AMPA receptors underwent clathrin-dependent endocytosis, which was accelerated by insulin in a GluR2 subunit-dependent manner. Insulin-stimulated endocytosis rapidly decreased AMPA receptor numbers in the plasma membrane, resulting in long-term depression (LTD) of AMPA receptor-mediated synaptic transmission in hippocampal CA1 neurons. Moreover, insulin-induced LTD and low-frequency stimulation-(LFS-) induced homosynaptic CA1 LTD were found to be mutually occlusive and were both blocked by inhibiting postsynaptic clathrin-mediated endocytosis. Thus, controlling postsynaptic receptor numbers through endocytosis may be an important mechanism underlying synaptic plasticity in the mammalian CNS.

Discordant MRI/FDG-PET imaging for the diagnosis of borderline ovarian tumors.

The objective of this study was to assess the role of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) for the characterization of ovarian masses that were diagnosed as ovarian malignancies by magnetic resonance imaging (MRI). We performed a retrospective review of eight patients with pathologically confirmed borderline ovarian tumors (BOT) who underwent MRI and FDG-PET before surgical staging from August 2005 to March 2007. We assessed the PET imaging of the BOT, measured the FDG uptake and quantified the findings as a standardized uptake value (SUV). The FDG-PET scans, of all eight patients, showed uptake of FDG with a mean SUV of less than 2.0 in the solid portion of the masses evaluated. We conclude that the MRI-PET differences may help differentiate borderline from malignant ovarian tumors.

Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization.

Internalization of postsynaptic AMPA receptors depresses excitatory transmission, but the underlying dynamics and mechanisms of this process are unclear. Using immunofluorescence and surface biotinylation, we characterized and quantified basal and regulated AMPA receptor endocytosis in cultured hippocampal neurons, in response to synaptic activity, AMPA and insulin. AMPA-induced AMPA receptor internalization is mediated in part by secondary activation of voltage-dependent calcium channels, and in part by ligand binding independent of receptor activation. Although both require dynamin, insulin- and AMPA-induced AMPA receptor internalization are differentially dependent on protein phosphatases and sequence determinants within the cytoplasmic tails of GluR1 and GluR2 subunits. AMPA receptors internalized in response to AMPA stimulation enter a recycling endosome system, whereas those internalized in response to insulin diverge into a distinct compartment. Thus, the molecular mechanisms and intracellular sorting of AMPA receptors are diverse, and depend on the internalizing stimulus.

GABAA receptor-associated phosphoinositide 3-kinase is required for insulin-induced recruitment of postsynaptic GABAA receptors.

Type A gamma-aminobutyric acid (GABAA) receptors mediate most of the fast inhibitory synaptic transmission within the vertebrate brain. The regulation of this inhibition is vital in modulating neural activity. One regulator of GABAA receptor function is insulin, which can serve to enhance GABAA receptor-mediated miniature inhibitory postsynaptic currents, via an increase in the number of receptors at the plasma membrane. We set out to investigate the molecular mechanisms involved in the insulin-induced potentiation of GABAA receptor-mediated responses, by examining the role of phosphoinositide 3-kinase (PI3-K), a key mediator of the insulin response within the brain. We found that PI3-K associates with the GABAA receptor, and this interaction is increased following insulin treatment. Additionally, the beta2 subunit of the GABAA receptor appears to mediate the insulin-stimulated association with the N-terminal SH2 domain of the p85 subunit of PI3-K. Our results imply a mechanism whereby insulin can regulate changes in synaptic transmission through its downstream actions on the GABAA receptor.

Non-steroidal anti-inflammatory drugs increase insulin release from beta cells by inhibiting ATP-sensitive potassium channels.

BACKGROUND AND PURPOSE: Some non-steroidal anti-inflammatory drugs (NSAIDs) incidentally induce hypoglycemia, which is often seen in diabetic patients receiving sulphonylureas. NSAIDs influence various ion channel activities, thus they may cause hypoglycemia by affecting ion channel functions in insulin secreting beta cells. This study investigated the effects of the NSAID meclofenamic acid (MFA) on the electrical excitability and the secretion of insulin from pancreatic beta cells. EXPERIMENTAL APPROACH: Using patch clamp techniques and insulin secretion assays, the effects of MFA on the membrane potential and transmembrane current of INS-1 cells, and insulin secretion were studied. KEY RESULTS: Under perforated patch recordings, MFA induced a rapid depolarization in INS-1 cells bathed in low (2.8 mM), but not high (28 mM) glucose solutions. MFA, as well as acetylsalicylic acid (ASA) and flufenamic acid (FFA), excited the cells by inhibiting ATP-sensitive potassium channels (K(ATP)). In whole cell recordings, K(ATP) conductance consistently appeared when intracellular ATP was diluted. Intracellular glibenclamide prevented the development of K(ATP) activity, whereas intracellular MFA had no effect. At low glibenclamide concentrations, MFA induced additional inhibition of the K(ATP) current. Live cell Ca(2+) imaging displayed that MFA elevated intracellular Ca(2+) at low glucose concentrations. Furthermore, MFA dose-dependently increased insulin release under low, but not high, glucose conditions. CONCLUSIONS AND IMPLICATIONS: MFA blocked K(ATP) through an extracellular mechanism and thus increased insulin secretion. As some NSAIDs synergistically inhibit K(ATP) activity together with sulphonylureas, the risk of NSAID-induced hypoglycemia should be considered when glucose-lowering compounds are administered.

Placenta increta after first-trimester dilatation and curettage manifesting as an unusual uterine mass: magnetic resonance findings.

Placenta increta during the first trimester of pregnancy is extremely rare. Only a few cases of placenta accreta during the latter half of pregnancy manifesting as a uterine mass have been published. This report describes a case of placenta increta that caused prolonged bleeding after a first-trimester abortion, and was identified by magnetic resonance imaging (MRI) as a heterogeneous mass in the myometrium. This is the first report of a placenta increta detected as a uterine mass after first-trimester dilatation and curettage, and its MRI findings.