Aging of Malbec wines from Mendoza and California: Evolution of phenolic and elemental composition.

This work aimed to investigate the evolution of phenolic compounds and elements during the aging of Malbec red wines from different regions of Mendoza (Argentina) and California (United States). The profiles of low molecular weight polyphenols and anthocyanins were analyzed using high-performance liquid chromatography with a diode-array detector (HPLC-DAD), and the elemental composition using microwave plasma-Atomic emission spectrometry (MP-AES). Through uni- and multivariate statistical analyses, the effects of aging time and region on wine were investigated. It was observed that aging time was a significant factor that affected the phenolic compound profile in the studied Malbec wines studied and that after five years of aging, the wines could be differentiated according to region. The results of this study may impact decisions made regarding the storage of Malbec wines in the future.

Developmental and Metabolic Plasticity of White-Skinned Grape Berries in Response to Botrytis cinerea during Noble Rot.

Noble rot results from exceptional infections of ripe grape (Vitis vinifera) berries by Botrytis cinerea. Unlike bunch rot, noble rot promotes favorable changes in grape berries and the accumulation of secondary metabolites that enhance wine grape composition. Noble rot-infected berries of cv Sémillon, a white-skinned variety, were collected over 3 years from a commercial vineyard at the same time that fruit were harvested for botrytized wine production. Using an integrated transcriptomics and metabolomics approach, we demonstrate that noble rot alters the metabolism of cv Sémillon berries by inducing biotic and abiotic stress responses as well as ripening processes. During noble rot, B. cinerea induced the expression of key regulators of ripening-associated pathways, some of which are distinctive to the normal ripening of red-skinned cultivars. Enhancement of phenylpropanoid metabolism, characterized by a restricted flux in white-skinned berries, was a common outcome of noble rot and red-skinned berry ripening. Transcript and metabolite analyses together with enzymatic assays determined that the biosynthesis of anthocyanins is a consistent hallmark of noble rot in cv Sémillon berries. The biosynthesis of terpenes and fatty acid aroma precursors also increased during noble rot. We finally characterized the impact of noble rot in botrytized wines. Altogether, the results of this work demonstrated that noble rot causes a major reprogramming of berry development and metabolism. This desirable interaction between a fruit and a fungus stimulates pathways otherwise inactive in white-skinned berries, leading to a greater accumulation of compounds involved in the unique flavor and aroma of botrytized wines.

Pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders across the lifespan.

This review outlines pharmacologic treatments for the behavioral symptoms associated with autism spectrum disorders (ASDs) in children, adolescents, and adults. Symptom domains include repetitive and stereotyped behaviors, irritability and aggression, hyperactivity and inattention, and social impairment. Medications covered include serotonin reuptake inhibitors (SRIs), mirtazapine, antipsychotics, psychostimulants, atomoxetine, α-2 agonists, D-cycloserine, and memantine. Overall, SRIs are less efficacious and more poorly tolerated in children with ASDs than in adults. Antipsychotics are the most efficacious drugs for the treatment of irritability in ASDs, and may be useful in the treatment of other symptoms. Psychostimulants demonstrate some benefit for the treatment of hyperactivity and inattention in individuals with ASDs, but are less efficacious and associated with more adverse effects compared with individuals with ADHD. D-cycloserine and memantine appear helpful in the treatment of social impairment, although further research is needed.

Pharmacotherapy to control behavioral symptoms in children with autism.

INTRODUCTION: Autistic disorder, Asperger's disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS) are pervasive developmental disorders (PDDs) frequently associated with behavioral symptoms that may require pharmacotherapy to manage. AREAS COVERED: Behavioral symptoms in children with autism include interfering repetitive behaviors, irritability, and hyperactivity and inattention, among others. The psychotropic medications examined in this review include: serotonin reuptake inhibitors, typical and atypical antipsychotics, medications used to treat attention-deficit/hyperactivity disorder, naltrexone, buspirone, divalproex sodium, lamotrigine, levetiracetam, memantine, mirtazapine, riluzole, pioglitazone, and topiramate. EXPERT OPINION: For the treatment of interfering repetitive behaviors, serotonin reuptake inhibitors demonstrate less efficacy and are more poorly tolerated in children with autism compared to adults. Antipsychotics are the most efficacious drugs for the treatment of irritability in children with autism and other PDDs. For the treatment of hyperactivity and inattention, psychostimulants demonstrate some benefit. However, they are overall less efficacious and cause more side effects in children with PDDs compared to typically developing children with attention-deficit/hyperactivity disorder. Results from double-blind, placebo-controlled trials of these agents and others for the treatment of the behavioral symptom domains described above will be discussed in this review.

2-Methoxy-3-isobutylpyrazine in grape berries and its dependence on genotype.

2-Methoxy-3-isobutylpyrazine (MIBP) contributes a bell pepper aroma to many grape cultivars and has a reported aroma threshold of ∼2 ng L(-1) in water. The purpose of this study was twofold: (1) develop a procedure using headspace solid phase micro-extraction combined with GC-MS in the selected ion monitoring mode (HS-SPME-GC-MS-SIM) for analysis of MIBP in grape berries, and (2) determine the location of MIBP biosynthesis in grapevines by approach grafting clusters of Vitis vinifera L. cvs Cabernet Sauvignon and Muscat blanc onto each other. The soluble solids and pH of the grape juice/homogenate matrix from different grape berry developmental stages influenced the method precision; therefore, quantification via the method of standard addition was used. Using our developed method, the limit of detection (LOD) and limit of quantitation (LOQ) of MIBP were 0.1 ng L(-1) and 2 ng L(-1), respectively, measured in a model juice and non-MIBP containing Chardonnay juice. Spiked recoveries averaged between 91% and 112% in Cabernet Sauvignon and Pinot noir homogenates and the overall relative standard deviation was less than 10%. The method was used to analyze MIBP in 29 grape cultivars and in fruit from clusters grafted to Cabernet Sauvignon or Muscat vines. Quantifiable levels were found only in Cabernet franc, Cabernet Sauvignon, Merlot, Sauvignon blanc and Semillon, providing information on the genetic connection for the occurrence of MIBP in grapes. No MIBP was detected in the berries of Muscat blanc clusters grafted onto Cabernet Sauvignon vines when sampled at fruit maturity. MIBP was detected in all berries of Cabernet Sauvignon regardless the graft configuration. The data indicate that MIBP or its precursors originate in the berry and its formation depends upon grape genotype.

Distal baclofen pump catheter migration associated with far-lateral paraspinal surgical placement.

Objectives. The increased rigidity and spasms implicit to patients being treated with baclofen provide a potential source of drug delivery system-related complications. Placement of the intrathecal catheter from the far-lateral paraspinal approach has been advocated to avoid catheter fracture as previously reported with a midline approach. A thin fascial layer and increased muscle bulk laterally could increase motion of catheters placed in this position. The authors report on a series of patients found to have spinal catheter migration out from the thecal sac following a far-lateral paraspinal surgical approach. Materials and Methods. The medical records of six consecutive patients who required revision of an intrathecal baclofen infusion system secondary to spinal catheter migration were included in this retrospective review. Each patient failed to respond to oral antispasmodic therapy and showed a positive response to a trial of intrathecal baclofen before initial pump implantation. Clinical notes and operative reports were reviewed. Results. All patients had a baclofen pump inserted with the intrathecal catheter placed through the far-lateral portion of the paraspinal musculature entering above the lumbar vertebral pedicle. In all cases, the spinal catheter migrated and was found coiled outside of the thecal sac. In two patients, this occurred on two separate occasions. Mean time to catheter revision following implantation was 7 ± 2 months. Conclusions. Spinal catheter migration from the subarachnoid space can occur with intrathecal baclofen infusion systems. Alternative methods for spinal catheter placement warrant further study.

'Catching' the concept of spiritual care: implementation of an education programme.

This article will outline the achievements of a project group as they translate the recommendations set out in the UK National Institute for Health and Clinical Excellence (NICE) guidance on spiritual care provision in clinical practice (NICE, 2004). It was evident that there was an opportunity to offer a comprehensive, competency-based course that developed recognition of the spiritual care needs of patients with cancer and their carers. A two-day experiential programme was devised that included role play, the evidence base, theory and fun, resulting in the acquisition of tacit and explicit knowledge. The course was based around the following tenets: Spiritual issues are broader than religious ones and include a quest for meaning in the illness, resolution of old conflicts and integration of past life experiences (Barraclough, 1994). We cannot know others except by knowing ourselves (Carrither, 1992). It is hoped that by providing holistic training that stimulates the growth of an individual's spirituality and allows them to identify their spiritual needs, we can increase understanding, awareness, confidence and knowledge in ways that can have a real application within the workplace, enabling spiritual care provision to become realistically integral to care.

Pulmonary surfactant proteins A and D directly suppress CD3+/CD4+ cell function: evidence for two shared mechanisms.

Pulmonary surfactant is a lipoprotein complex that lowers surface tension at the air-liquid interface of the lung and participates in pulmonary host defense. Surfactant proteins (SP), SP-A and SP-D, modulate a variety of immune cell functions, including the production of cytokines and free radicals. Previous studies showed that SP-A and SP-D inhibit lymphocyte proliferation in the presence of accessory cells. The goal of this study was to determine whether SP-A and SP-D directly suppress Th cell function. Both proteins inhibited CD3(+)/CD4(+) lymphocyte proliferation induced by PMA and ionomycin in an IL-2-independent manner. Both proteins decreased the number of cells entering the S and mitotic phases of the cell cycle. Neither SP-A nor SP-D altered cell viability, apoptosis, or secretion of IL-2, IL-4, or IFN-gamma when Th cells were treated with PMA and ionomycin. However, both proteins attenuated ionomycin-induced cytosolic free calcium ([Ca(2+) ](i)), but not thapsigargin-induced changes in [Ca(2+)](i). In summary, inhibition of T cell proliferation by SP-A and SP-D occurs via two mechanisms, an IL-2-dependent mechanism observed with accessory cell-dependent T cell mitogens and specific Ag, as well as an IL-2-independent mechanism of suppression that potentially involves attenuation of [Ca(2+)](i).

CD83 expression influences CD4+ T cell development in the thymus.

T lymphocyte selection and lineage commitment in the thymus requires multiple signals. Herein, CD4+ T cell generation required engagement of CD83, a surface molecule expressed by thymic epithelial and dendritic cells. CD83-deficient (CD83-/-) mice had a specific block in CD4+ single-positive thymocyte development without increased CD4+CD8+ double- or CD8+ single-positive thymocytes. This resulted in a selective 75%-90% reduction in peripheral CD4+ T cells, predominantly within the naive subset. Wild-type thymocytes and bone marrow stem cells failed to differentiate into mature CD4+ T cells when transferred into CD83-/- mice, while CD83-/- thymocytes and stem cells developed normally in wild-type mice. Thereby, CD83 expression represents an additional regulatory component for CD4+ T cell development in the thymus.

Influence of CD4 T cells and the source of major histocompatibility complex class II-restricted peptides on cytotoxic T-cell priming by dendritic cells.

We have previously reported that bone marrow derived dendritic cells (DC) pulsed with major histocompatibility complex (MHC) class I-restricted peptide efficiently prime a cytotoxic T lymphocyte (CTL) response in vivo. Here we assess the involvement of CD4(+) T cells in the induction of CD8(+) CTL by DC by testing the ability of class II-deficient (C2D) DC, class II mutant (Alpha beta mut) DC and autologous serum generated DC (AS DC) to present class I-restricted antigens in vitro and in vivo. DC generated from the bone marrow of class II knockout mice and transgenic mice expressing a mutant class II that can not bind CD4 were phenotypically similar to wild type (wt) DC, except with regard to MHC class II expression. The C2D and Alpha beta mut DC, though fully capable of presenting the class I-restricted ovalbumin (OVA) peptide to a T-cell hybridoma in vitro, failed to prime a CTL response in vivo. Restoration of class II expression on C2D DC allowed priming of a CTL response; thus, the defect in CTL priming was indeed caused by the absence of class II expression. Likewise, DC generated in autologous serum were unable to prime a CTL response as these DC only express 'self' class II epitopes and therefore would not activate syngeneic CD4(+) T cells. Addition of exogenous class II epitopes rescued the ability of AS DC to prime a CTL response. These observations provide convincing evidence that efficient CTL induction by DC in vivo requires concomitant presentation of class II epitopes for CD4(+) T-cell induction.