Pioglitazone and rosiglitazone have different effects on serum lipoprotein particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia.

Objective: Associated with insulin resistance in type 2 diabetes are increased serum triglycerides, decreased HDL cholesterol, and a predominance of large VLDL, small LDL, and small HDL particles. The comparative effects of thiazolidinedione insulin sensitizers on serum lipoprotein particle concentrations and sizes in type 2 diabetes are not known. We studied the effects of pioglitazone (PIO) and rosiglitazone (ROSI) treatments on serum lipoprotein particle concentrations and sizes in type 2 diabetic patients with dyslipidemia.

Treatment of naming in nonfluent aphasia through manipulation of intention and attention: a phase 1 comparison of two novel treatments.

Twenty-three chronic nonfluent aphasia patients with moderate or severe word-finding impairments and 11 with profound word-finding impairments received two novel picture-naming treatments. The intention treatment initiated picture-naming trials with a complex left-hand movement and was designed to enhance right frontal participation during word retrieval. The attention treatment required patients to view visual stimuli for picture-naming trials in their left hemispace and was designed to enhance right posterior perisylvian participation during word retrieval.

The effects of antidepressants on cyclic AMP-response element-driven gene transcription in a model cell system.

The effects of the antidepressant drugs clomipramine (CLOM), desipramine (DMI), tianeptine (TIAN) and of norfluoxetine (NORF, the active metabolite of fluoxetine), were investigated in CHO cells expressing human beta2 adrenoceptors and a secreted placental alkaline phosphatase (SPAP) reporter gene to determine their actions on cyclic AMP-driven gene transcription. After 18 h of exposure, CLOM, DMI and NORF, but not TIAN, had biphasic effects on 1 microM isoprenaline-stimulated SPAP fsproduction with concentrations between 10 nM and 1 microM enhancing the maximal (E(max)) SPAP response, without changing EC50 values, but higher concentrations produced marked inhibitory effects. At nanomolar concentrations, CLOM and DMI increased expression of phospho-CREB (cyclic AMP response element binding protein).

Why consider impaired social language usage in a case of corticobasal degeneration?

The purpose of this case study was to examine the integrity of cognitive skills, language usage, and language structure components in a patient with corticobasal degeneration (CBD). CBD is a levadopa-nonresponsive, degenerative neurologic movement disorder that is generally accompanied by cognitive (frontal executive dysfunction, dementia) and linguistic (aphasia) disorders. However, no one has reported on social language usage deficits in cases of CBD.

Accelerated formation of multicellular 3-D structures by cell-to-cell cross-linking.

The three-dimensional (3-D) arrangement of cells within tissues is integral to their development and function. Advances in stem cell science and regenerative medicine have stimulated interest in the replication of this architecture in vitro. We have developed a versatile method for controlling short-term cell-cell and cell-matrix interactions via a facile cell surface engineering process that enables the rapid formation of specific 3-D interactions for a range of cell types.

Effects of inhibition of fatty acid amide hydrolase vs. the anandamide membrane transporter on TRPV1-mediated calcium responses in adult DRG neurons; the role of CB receptors.

The aim of the present study was to investigate the relationship between TRPV1 stimulation and endocannabinoid-driven CB(1) receptor-mediated inhibition of activity in adult rat dorsal root ganglion (DRG) neurons, a model of primary afferent nociceptors. Calcium-imaging studies were performed to compare the effects of the fatty acid amide hydrolase (FAAH) inhibitor URB597 (1 microm) vs. the anandamide (AEA) uptake inhibitor UCM707 (1 microm) on capsaicin (100 nm) and N-arachidonoyl dopamine (NADA; 1 microm)-evoked changes in intracellular calcium [Ca(2+)](i) in DRG neurons.

Vanilloid receptor agonists and antagonists are mitochondrial inhibitors: how vanilloids cause non-vanilloid receptor mediated cell death.

Time-lapse photomicroscopy of human H460 lung cancer cells demonstrated of the transient receptor potential V1 (TRPV1) channel agonists, (E)-capsaicin and resiniferatoxin, and the TRPV1 antagonists, capsazepine, and SB366791, were able to bring about morphological changes characteristic of apoptosis and/or necrosis. Immunoblot analysis identified immunoreactivity for the transient receptor potential V1 (TRPV1) channel in rat brain samples, but not in rat heart mitochondria or in H460 cells. In isolated rat heart mitochondria, all four ligands caused concentration-dependent decreases in oxygen consumption and mitochondrial membrane potential.

Analgesic effects of fatty acid amide hydrolase inhibition in a rat model of neuropathic pain.

Cannabinoid-based medicines have therapeutic potential for the treatment of pain. Augmentation of levels of endocannabinoids with inhibitors of fatty acid amide hydrolase (FAAH) is analgesic in models of acute and inflammatory pain states. The aim of this study was to determine whether local inhibition of FAAH alters nociceptive responses of spinal neurons in the spinal nerve ligation model of neuropathic pain.

Chloroplast SecA and Escherichia coli SecA have distinct lipid and signal peptide preferences.

Like prokaryotic Sec-dependent protein transport, chloroplasts utilize SecA. However, we observe distinctive requirements for the stimulation of chloroplast SecA ATPase activity; it is optimally stimulated in the presence of galactolipid and only a small fraction of anionic lipid and by Sec-dependent thylakoid signal peptides but not Escherichia coli signal peptides.

Quantitative profiling of endocannabinoids and related compounds in rat brain using liquid chromatography-tandem electrospray ionization mass spectrometry.

A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is described for the simultaneous identification and quantification of eight endocannabinoid (EC) or related "entourage" compounds in rat brain tissue. Analytes were extracted and purified from rat brain tissue using an ethyl acetate/hexane solvent extraction, followed by a solid phase extraction (SPE) protocol. Chromatographic separation was achieved using a gradient elution, with a mobile phase of acetonitrile, formic acid, and ammonium acetate, at pH 3.

Understanding team adaptation: a conceptual analysis and model.

This endeavor provides a multidisciplinary, multilevel, and multiphasic conceptualization of team adaptation with theoretical roots in the cognitive, human factors, and industrial-organizational psychology literature. Team adaptation and the emergent nature of adaptive team performance are defined from a multilevel, theoretical standpoint. An input-throughput-output model is advanced to illustrate a series of phases unfolding over time that constitute the core processes and emergent states underlying adaptive team performance and contributing to team adaptation.

Selective photoaffinity labeling identifies the signal peptide binding domain on SecA.

SecA, an ATPase crucial to the Sec-dependent translocation machinery in Escherichia coli, recognizes and directly binds the N-terminal signal peptide of an exported preprotein. This interaction plays a central role in the targeting and transport of preproteins via the SecYEG channel. Here we identify the signal peptide binding groove (SPBG) on SecA addressing a key issue regarding the SecA-preprotein interaction.

Is the metabolic syndrome a real clinical entity and should it receive drug treatment?

Metabolic syndrome represents a cluster of risk factors commonly associated with obesity and diabetes that in turn are associated with an increased risk of cardiovascular disease. The worldwide prevalence of metabolic syndrome, obesity, and diabetes is on the rise, leading to serious public health concerns surrounding the downstream consequences in the form of premature cardiovascular disease. In this review, we examine the debate surrounding the characterization and diagnosis of metabolic syndrome and discuss potential treatment options.

Cannabinoids and PPARalpha signalling.

Cannabinoids have been shown to possess anti-inflammatory and neuroprotective properties, which were proposed to occur mainly via activation of the G-protein-coupled receptor CB(1) (cannabinoid receptor 1). Recently, certain cannabinoids have been reported to be ligands for members of the nuclear receptor transcription factor superfamily known as PPARs (peroxisome-proliferator-activated receptors). This review summarizes the evidence for cannabinoid activation of PPARs and identifies a new intracellular target for cannabinoids as therapeutic agents for neuroprotective treatment.

A pilot study of use-dependent learning in the context of Constraint Induced Language Therapy.

This investigation reports the results of a pilot study concerning the application of principles of use-dependent learning developed in the motor rehabilitation literature as Constraint Induced Therapy to language rehabilitation in a group of individuals with chronic aphasia. We compared treatment that required forced use of the language modality, Constraint Induced Language Therapy, (CILT) to treatment allowing all modes of communication. Both treatments were administrated intensively in a massed practice paradigm, using the same therapeutic stimuli and tasks.

Influence of intensive phonomotor rehabilitation on apraxia of speech.

In this phase I rehabilitation study, we investigated the effects of an intensive phonomotor rehabilitation program on verbal production in a 73-year-old male, 11 years postonset a left-hemisphere stroke, who exhibited apraxia of speech and aphasia. In the context of a single-subject design, we studied whether treatment would improve phoneme production and generalize to repetition of multisyllabic words, words of increasing length, discourse, and measures of self-report. We predicted that a predominant motor impairment would respond to intensive phonomotor rehabilitation.

Treatability of different components of aphasia - insights from a case study.

In this phase I clinical rehabilitation study, we investigated the effects of phonological rehabilitation for alexia and aphasia in an individual 54 years after a left-hemisphere ischemic infarction. In the context of a single-subject design, we studied whether treatment would improve phonological processing, reading, and generalization to untreated behaviors. While results showed a lack of generalization to real-word reading aloud, improvement was present in phonological processing, language function (Western Aphasia Battery Aphasia Quotient, Boston Naming Test, Reading Comprehension Battery for Aphasia), and auditory processing (Revised Token Test).

Effect of a viscous fiber bar on postprandial glycemia in subjects with type 2 diabetes.

Objective: To compare the effect of an experimental viscous fiber (VF) crispy bar on the postprandial glucose, insulin, and C-peptide response in adult subjects with type 2 diabetes to two commercially available control crispy bars.

Design: The study was a randomized, double-blinded, three period, crossover study.

Setting: The study was conducted at two sites: Park Nicollet Institute, International Diabetes Center, Minneapolis, MN, and Radiant Research, Inc.

Management of Type 2 diabetes: the role of incretin mimetics.

Type 2 diabetes is characterised by insulin resistance and progressive beta-cell dysfunction (which leads to hyperglycaemia), the risk of progressive worsening of glycaemic control and an increased risk of both macrovascular and microvascular complications. Existing treatment strategies target deficient insulin secretion and insulin resistance, but do not generally address the underlying progressive beta-cell dysfunction that is common to Type 2 diabetes. Traditionally, Type 2 diabetes is first treated with medical nutrition therapy (reduced food intake and increased physical activity), followed by stepwise addition of oral antidiabetes therapies and, ultimately, exogenous insulin, as required.

Oligomeric states of the SecA and SecYEG core components of the bacterial Sec translocon.

Many proteins synthesized in the cytoplasm ultimately function in non-cytoplasmic locations. In Escherichia coli, the general secretory (Sec) pathway transports the vast majority of these proteins. Two fundamental components of the Sec transport pathway are the SecYEG heterotrimeric complex that forms the channel through the cytoplasmic membrane, and SecA, the ATPase that drives the preprotein to and across the membrane.

Progressive oculo-orofacial-speech apraxia (POOSA).

A loss of speech can be related to disorders of the motor units (paresis), language deficits (aphasia), or speech programming deficits (apraxia of speech). Although apraxia of speech has been reported to be associated with degenerative diseases, we observed a patient with a unique constellation of signs that included apraxia of speech, oculo-orofacial apraxia and a supranuclear ophthalmoplegia in the absence of extrapyramidal (Parkinsonian) signs. Post-mortem examination revealed a loss of neurons in the frontal and temporal regions, but there was also a marked loss of neurons and astrogliosis in the caudate, claustrum, globus pallidus, substantia nigra, and loss of axons in the anterior cerebral peduncles.

A cannabinoid receptor 1 mutation proximal to the DRY motif results in constitutive activity and reveals intramolecular interactions involved in receptor activation.

Activation of a G-protein-coupled receptor involves changes in specific microdomain interactions within the transmembrane region of the receptor. Here, we have focused on the role of L207, proximal to the DRY motif of the human cannabinoid receptor 1 in the interconversion of the receptor resting and active states. Ligand binding analysis of the mutant receptor L207A revealed an enhanced affinity for agonists (three- to six-fold) and a diminished affinity for inverse agonists (19- to 35-fold) compared to the wild-type receptor, properties characteristic of constitutive activity.

Integrated tobacco cessation counseling in a diabetes self-management training program: a randomized trial of diabetes and reduction of tobacco.

Purpose: The purpose of this study was to evaluate the impact of a tobacco cessation intervention using motivational interviewing on smoking cessation rates during diabetes self-management training (DSMT).

Methods: A randomized controlled trial was conducted with subjects recruited from an ongoing type 2 diabetes adult education program at a large diabetes center. A total of 114 subjects were randomized to intervention (n = 57; face-to-face motivational interviewing plus telephone counseling and offering of medication) or standard care (n = 57).

Incretin mimetics and dipeptidyl peptidase-IV inhibitors: a review of emerging therapies for type 2 diabetes.

Type 2 diabetes is thought to develop as a result of progressive beta-cell dysfunction in the setting of insulin resistance, leading to increased risks of microvascular and macrovascular complications. Type 2 diabetes is currently treated with diet and exercise, followed by oral drug therapy, and finally exogenous insulin. While this approach is known to improve glycemic control, none of the currently available therapies significantly improve beta-cell function.