Metabolic and ovarian effects of rosiglitazone treatment for 12 weeks in insulin-resistant women with polycystic ovary syndrome

BACKGROUND: Insulin sensitizers have favourable metabolic and ovarian effects in polycystic ovary syndrome (PCOS). This study examined rosiglitazone, a thiazolidinedione, in PCOS. METHODS: In a prospective, open-label study, the effects of rosiglitazone on metabolism and ovarian function were examined in 42 non-diabetic women with PCOS classified according to the National Institute of Child Health and Human Development criteria and insulin resistance (IR) by steady-state plasma glucose (SSPG) > or =10 mmol/l on octreotide-modified insulin suppression testing. Participants were randomized to rosiglitazone 2, 4 or 8 mg daily for 12 weeks. Endpoints included ovulation and menstrual pattern; serum testosterone, sex hormone-binding globulin (SHBG), and LH; and changes in IR and glucose-insulin responses on 8 h mixed-meal profile. RESULTS: After rosiglitazone 8 mg daily for 12 weeks, SSPG declined and insulinaemia fell by 46%; lower doses gave lesser effects. Serum LH, total and free testosterone were unchanged; SHBG increased. With rosiglitazone, ovulation occurred in 23/42 women (55%), without significant dose dependence. Both before and during treatment, ovulators on rosiglitazone had lower circulating insulin and free testosterone and higher SHBG than non-ovulators. Testosterone declined only in a subgroup of ovulators with early vaginal bleeding after starting rosiglitazone. CONCLUSIONS: Rosiglitazone in insulin-resistant PCOS promoted ovulation and dose-dependently decreased IR and insulinaemia; ovulators had lower circulating insulin and testosterone.     

Iatrogenic Foreign Materials Associated with Retrieved Clot Tissue via Mechanical Thrombectomy

BACKGROUND AND PURPOSE:Hydrophilic polymers and polytetrafluoroethylene liners, commonly used in the construction of endovascular devices, occasionally separate from devices with subsequent embolization. We determined the frequency of such materials in thrombus specimens retrieved by mechanical thrombectomy in patients with stroke.MATERIALS AND METHODS:We retrospectively reviewed H&E–stained thrombus sections for presence and types of foreign materials. We identified 4 types of foreign materials—Type I: material was light green with refraction and had a homogeneous texture; type II: material was light gray and/or dark gray, thin, and loose or attenuated in texture; type III: material was light green with refraction, solitary in texture, irregular in shape, and was often associated with round or oval bubblelike particles and/or diffuse black particles; and type IV: material had homogeneous texture and was light pink or red. In addition, polymer materials from different layers of used mechanical thrombectomy catheters were compared with the foreign materials found in thrombus specimens.RESULTS:A total of 101 thrombi were evaluated. Foreign materials were found in 53 (52.5%) thrombus samples. The most common type was type I (92%), followed by type II (30%). The histopathologic features of the polymer materials from mechanical thrombectomy catheters were similar to the foreign materials found in thrombus specimens. The inner polytetrafluoroethylene liner and coating layer of catheters resembled type I and type II of the foreign materials, respectively.CONCLUSIONS:Foreign polymer materials are present in approximately half of retrieved thrombi, most commonly polytetrafluoroethylene from catheter liners and less from hydrophilic coatings.

Neuroendovascular catheters are constructed with various polymers aimed at improving lubricity, including polytetrafluoroethylene (PTFE) liners and hydrophilic coatings. The benefits of these materials include low coefficients of friction, improved trackability during the endovascular procedure, easy lesion passage, and vasospasm prevention.¹ However, introduction of such foreign material to the body is associated with some risks. Many reports have suggested that foreign materials could dissociate from catheters with subsequent distal embolization and microinfarctions.^2,3In the current study, we performed histologic examination of 101 thrombus specimens to evaluate how often polymer materials are liberated from catheters. All of the thrombus samples were retrieved by mechanical thrombectomy (MT) from patients with large-vessel occlusion stroke. To confirm the source of the foreign materials observed in thrombi, we examined the histologic appearance of each polymer layer of the aspiration catheters commonly used in thrombectomy, and compared the histology with that of the foreign materials observed in thrombus specimens.     

PAMAM Dendrimer-Baculovirus Nanocomplex for Microencapsulated Adipose Stem Cell-Gene Therapy: In Vitro and in Vivo Functional Assessment

The present study aims to develop a new stem cell based gene delivery system consisting of human adipose tissue derived stem cells (hASCs) genetically modified with self-assembled nanocomplex of recombinant baculovirus and PAMAM dendrimer (Bac-PAMAM) to overexpress the vascular endothelial growth factor (VEGF). Cells were enveloped into branched PEG surface functionalized polymeric microcapsules for efficient transplantation. In vitro analysis confirmed efficient transduction of hASCs expressing 7.65 ± 0.86 ng functionally active VEGF per 10(6) microencapsulated hASCs (ASC-VEGF). To determine the potential of the developed system, chronically infarcted rat hearts were treated with either empty microcapsules (MC), microencapsulated hASCs expressing MGFP reporter protein (MC+ASC-MGFP), or MC+ASC-VEGF, and analyzed for 10 weeks. Post-transplantation data confirmed higher myocardial VEGF expressions with significantly enhanced neovasculature in the MC+ASC-VEGF group. In addition, the cardiac performance, as measured by percentage ejection fraction, also improved significantly in the MC+ASC-VEGF group (48.6 ± 6.1%) compared to that in MC+ASC-MGFP (38.8 ± 5.3%) and MC groups (31.5 ± 3.3%). Collectively, these data demonstrate the feasibility of this system for improved stem cell therapy applications.     

Changes of cytosolic calcium and contractility of young rat vas deferens by acute treatment with amphetamine, fluoxetine or sibutramine

Procyanidins, which are condensed catechins, have been elucidated as absorbable polyphenols, but their health-benefits remain unclear. The aim of this study was, thus, to clarify the efficacy and mechanism of each procyanidin oligomer in NO activation in rat aortic endothelial cells (RAECs). Treatment of RAECs with 50μM procyanidin C1 (4β→8 trimer) resulted in a time- and dose-dependent hyperpolarization using the membrane potential-sensitive probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, while no effect was observed for (-)-epicatechin (a monomer) and procyanidin B2 (4β→8 dimer). The C1-induced hyperpolarization was inhibited by iberiotoxin, a specific inhibitor of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel, as well as 2-aminoethyl diphenylborinate (2-APB), a store-operated Ca(2+) entry inhibitor. Procyanidin C1 caused a significant increase in NO production from RAECs via phosphorylation of both eNOS and Akt, and the effect was completely inhibited by N(G)-monomethyl-l-arginine or combined treatment with iberiotoxin and the phosphatidylinositol 3-kinase (PI3K) specific inhibitor, wortmannin, as well as combined treatment with 2-APB and wortmannin. Taken together, these findings provide critical evidence that procyanidin C1, but not B2, has potential to induce NO production in RAECs via both Ca(2+)-dependent BK(Ca) channel-mediated hyperpolarization and Ca(2+)-independent PI3K/Akt pathways.     

Agmatine protects against scopolamine-induced water maze performance impairment and hippocampal ERK and Akt inactivation

Cholinergic brain activity plays a significant role in memory. Scopolamine a muscarinic cholinergic antagonist is known to induce impairment in Morris water maze performance, the task which is mainly dependent on the hippocampus. It is suggested that hippocampal ERK and Akt activation play roles in synaptic plasticity and some types of learning and memory. Agmatine, a polyamine derived from l-arginine decarboxylation, is recently shown to exert some neuroprotective effects. This study was aimed to investigate if agmatine could reverse scopolamine-induced memory impairment and possible hippocampal ERK and Akt activity alteration. Adult male Sprague-Dawley rats weighing 200-250 g were randomly assigned into 5 groups. The animals were trained for 3 days in Morris water maze and in day 4 their memory retention was assessed in probe trial which was consisted of a 60 s trial with no platform. Scopolamine (1 mg/kg/ip) or saline were injected 30 min and agmatine (20 or 40 mg/kg/ip) was administered 60 min before each session. The hippocampi were isolated after behavioral studies and western blotting studies on hippocampal lysates were done to determine the levels of activated ERK and Akt. Scopolamine treatment not only impaired water maze learning and memory, but also decreased the amount of phosphorylated (activated) ERK and Akt. Agmatine pre-treatment prevented both the learning impairment and hippocampal ERK and Akt inactivation induced by scopolamine. It seems that agmatine may act as a candidate substance against amnesia.