Therapeutic azulenyl nitrone antioxidants

The reactions of nitrones with free radicals have been widely studied both in vitro and in vivo. In comparison to classical chain-breaking phenolic antioxidants (such as Vitamin E and butylated hydroxytoluene [BHT]), conventional phenyl-substituted nitrones have much higher oxidation potentials. Azulenyl-substituted nitrones have lower oxidation potentials than conventional nitrones and react efficiently with free radicals in vitro and in vivo. The design and synthesis of novel azulenyl nitrones with yet lower oxidation potentials, prepared from commercially available guaiazulene, has produced several 1,2-trans -bis-azulenyl ethene compounds with enhanced antioxidant activity. A convenient 1H NMR-based assay for assessing the potency of chain-breaking antioxidants has shown these novel nitrones to be more than 300 times more potent in inhibiting the free radical-mediated aerobic peroxidation of cumene than α-phenyl-N-tert-butyl nitrone (PBN) and the experimental stroke drug NXY-059. The low oxidation potential of these novel nitrones and the stability of the corresponding radical cation have been implicated in the explanation of the increased antioxidant potency of these second generation azulenyl nitrones. Based on the results of these in vitro studies, the first of these novel compounds, stilbazulenyl nitrone (STAZN), was investigated in animal models of disease known to involve free radical-mediated pathology. In view of STAZN's marked lipophilicity and anticipated blood brain barrier permeability, neurodegenerative conditions were investigated. All animal experiments were performed at the University of Miami by members of the Ginsberg research group. STAZN was neuroprotective in traumatic brain injury in rats. It also provided exceptional neuroprotection in an animal model of stroke. The concentration of STAZN required for neuroprotection was 300–600 times less than doses of PBN or NXY-059 required for similar effect. Thus, the benefits of greater antioxidant potency sought by lowering the oxidation potential of nitrones appear to have been reaped both in vitro and in vivo. In spite of the challenges and difficulties in understanding free radical-mediated pathology, this work establishes that considerations such as redox potential and lipophilicity can provide a very fruitful rationale for the design of therapeutic azulenyl nitrone antioxidants. ^

The Impact of Workshops on the Quality and Quantity of Parent-Child Booksharing Skills

A pilot study posits that conducting a number of literacy workshops with teenage mothers translated into a greater number of appropriate booksharing skills implemented while reading to the child. The results of one- and two-way ANOVAs and of a contingency table with crosstabs are included.

Changing Parental Perceptions of Math and Science Curriculum Through Hands-on Workshops

Many parents hold negative perceptions of math and science because they have never been taught these domains from a hands-on, constructivist approach. Only 20 - 30% of adults have actually experienced activity-based science inquiry. Instead, these individuals were exposed to didactic science programs that emphasize drill, skill and memorization (Shymanksy, 2000). This has had a negative impact upon their content knowledge in these areas and their perceptions of math and science. Consequently, parents are hesitant to incorporate math and science into their home life. There is a dire need to determine if parental perceptions of math, science, and their content knowledge will be positively effected as a result of participation in hands-on science workshops.

The therapeutic effects of Millon Clinical Multiaxial Inventory -III assessment feedback

A study was conducted to test the therapeutic effects of assessment feedback on rapport-building and self-enhancement variables (self-verification, self-discovery, self-esteem), as well as symptomatology. Assessment feedback was provided in the form of interpretive information based on the results of the Millon Clinical Multiaxial Inventory-III (MCMI-III). Participants (N = 89) were randomly assigned to three groups: a Feedback group, a Reflective-Counseling group, and a No-Feedback group. The Feedback group was provided with assessment feedback, the Reflective-Counseling group was asked to comment on the meaning of the taking the MCMI-III, the No-Feedback group received general information about the MCMI-III. Results revealed that assessment feedback, when provided in the form of interpretive interpretation positively affects rapport-building and self-enhancement variables (self-verification and self-discovery). No significant results were found in terms of self-esteem or symptom decrease as a function of feedback. However, a significant decrease in symptoms across groups was found. Results indicate that assessment feedback in the form of interpretive information can be used as a starting point in therapy. Implications of the findings are discussed with respect to theory and clinical practice. ^

The therapeutic effects of Millon Clinical Multiaxial Inventory-III assessment feedback

A study was conducted to test the therapeutic effects of assessment feedback on rapport-building and self-enhancement variables (self-verification, self-discovery, self-esteem), as well as symptomatology. Assessment feedback was provided in the form of interpretive information based on the results of the Millon Clinical Multiaxial Inventory- III (MCMI-III). Participants (N = 89) were randomly assigned to three groups: a Feedback group, a Reflective-Counseling group, and a No-Feedback group. The Feedback group was provided with assessment feedback, the Reflective-Counseling group was asked to comment on the meaning of the taking the MCMI-III, the No- Feedback group received general information about the MCMI-III. Results revealed that assessment feedback, when provided in the form of interpretive interpretation positively affects rapport-building and self-enhancement variables (self-verification and self-discovery). No significant results were found in terms of self-esteem or symptom decrease as a function of feedback. However, a significant decrease in symptoms across groups was found. Results indicate that assessment feedback in the form of interpretive information can be used as a starting point in therapy. Implications of the findings are discussed with respect to theory and clinical practice.

The effects of therapeutic ultrasound on open wounds

The purpose of this study was to evaluate the evidence for the effectiveness of therapeutic ultrasound (US) therapy in the treatment of open wounds as an adjunct to the usual and customary treatment provided by physical therapists. An exhaustive search of all published studies on the effects of therapeutic ultrasound on open wounds was performed. Every article, which met certain criteria, was reviewed in detail. Criteria included the use of human subjects, animal subjects, or human cells in vitro, publication in referred journals indexed by MEDLINE, CINAHL and availability of full text in the English language. Fourteen studies met the selection criteria. A total of 31 possible outcomes were available from these studies. Outcomes were categorized as positive, negative or non-significant. The results indicated a total of seventeen positives, eight negatives and six non-significant outcomes. The results of the analysis indicate that there is evidence in the literature to suggest that therapeutic US is beneficial in the treatment of open wounds.

Serviços-escola de psicologia do Rio Grande do Norte: formação profissional e política pública de saúde em debate

The Psychology University Services is stablished normatively as an indispensable equipment to the recognition of the graduation courses of psychologists by the Brazilian Education Ministery. The Public Healthcare Policies (Universal Health System/SUS) constitutes itself as a input field of the professional category, but shows huge challenges in the formation of these professionals. The objective of this work is to analyse the functioning of the Psychology University Services (SEP) and the Superior Educational Institutions from Natal, understood as important formation devices to attend the actual demands of the psychologist's work on SUS. For this, it sought a) characterize the psychological practices developed in the SEP; b) relate the National Curricular Lines of Direction of the psychology courses to the skills and competences developed in the SEP to the performance on the public healthcare policies; c) mapping ways of including the SEP in the network designed by the healthcare policy. Interviews were performed with 13 academic supervisors, 8 field supervisors and technicians of superior level (TNC), along with 9 managers, being for of the Psychology University Services and 5 of the graduation programs. Questionnaires were also applied to 57 interns and 24 graduates. Besides that, two conversation circles were performed with the faculty and technician members from two of the Educational Institutions that were participating of the research, as well as a workshop with students and psychologists, promoted by the CRP 17. We observed that most part of the faculty members and managers know the DCN and comprehend that the formation is in process of change in what concerns to the extension of the formation to the performance of the psychologists in various contexts. However, most part of the TNC don't know about them. Moreover, the results point to the predominance of the assisting model based on the traditional clinic psychology, although the articulation with the public healthcare and social assistance networks can already be timidly visualized. Different modalities of practices in theses Psychology University Services were also detected, such as conversation groups, thematic workshops, organizational consultancies, team meetings with the interns and TNS in a daily basis, matriciament in mental health, therapeutic monitoring, among others. Yet, the SEP in Rio Grande do Norte are still isolated from the other courses that perform in the healthcare area and also from the services that compose the public healthcare and public policies.

Jean Powell of P.O.N.Y. (Prostitutes of NY) speaks to women at "prostitution rights" workshops women's fair

General note: Title and date provided by Bettye Lane.

Rho-kinase as a therapeutic target in vascular diseases:striking nitric oxide signaling

Rho GTPases are a globular, monomeric group of small signaling G-protein molecules. Rho-associated protein kinase/Rho-kinase (ROCK) is a downstream effector protein of the Rho GTPase. Rho-kinases are the potential therapeutic targets in the treatment of cardiovascular diseases. Here, we have primarily discussed the intriguing roles of ROCK in cardiovascular health in relation to nitric oxide signaling. Further, we highlighted the biphasic effects of Y-27632, a ROCK inhibitor under shear stress, which acts as an agonist of nitric oxide production in endothelial cells. The biphasic effects of this inhibitor raised the question of safety of the drug usage in treating cardiovascular diseases.

Service users experiences of a therapeutic group programme in an acute psychiatric inpatient unit.

Psychiatric nurses have been facilitating therapeutic groups in acute psychiatric inpatient units for many years; however, there is a lack of nursing research related to this important aspect of care. This paper reports the findings of a study which aimed to gain an understanding of service users' experiences in relation to therapeutic group activities in an acute inpatient unit. A qualitative descriptive study was undertaken with eight service users in one acute psychiatric inpatient unit in Ireland. Data were collected using in-depth semi-structured interviews and analysed using Burnard's method of thematic content analysis. Several themes emerged from the findings which are presented in this paper.

A Therapeutic Antibody for Cancer, Derived from Single Human B Cells.

Some patients with cancer never develop metastasis, and their host response might provide cues for innovative treatment strategies. We previously reported an association between autoantibodies against complement factor H (CFH) and early-stage lung cancer. CFH prevents complement-mediated cytotoxicity (CDC) by inhibiting formation of cell-lytic membrane attack complexes on self-surfaces. In an effort to translate these findings into a biologic therapy for cancer, we isolated and expressed DNA sequences encoding high-affinity human CFH antibodies directly from single, sorted B cells obtained from patients with the antibody. The co-crystal structure of a CFH antibody-target complex shows a conformational change in the target relative to the native structure. This recombinant CFH antibody causes complement activation and release of anaphylatoxins, promotes CDC of tumor cell lines, and inhibits tumor growth in vivo. The isolation of anti-tumor antibodies derived from single human B cells represents an alternative paradigm in antibody drug discovery.

Targeting protein tyrosine phosphatase SHP2 for therapeutic intervention

Protein tyrosine phosphatases have been the focus of considerable research efforts aimed at developing novel therapeutics; however, these targets are often characterized as being ‘undruggable’ due to the challenge of achieving selectivity, potency and cell permeability. More recently, there has been renewed interest in developing inhibitors of the tyrosine phosphatase SHP2 (PTPN11) in the light of its broad role in cancer, specifically juvenile myelomonocytic leukemia, and recent studies that implicate SHP2 as a key factor in breast cancer progression. Recent significant advances in the field of SHP2 inhibitor development raise the question: are we on the verge of a new era of protein tyrosine phosphatase-directed therapeutics? This article critically appraises recent developments, assesses ongoing challenges and presents a perspective on possible future directions.

Swellable polymer films containing Au nanoparticles for point-of-care therapeutic drug monitoring using surface-enhanced Raman spectroscopy

Large (10 × 10 cm) sheets of surface-enhanced Raman spectroscopy (SERS) active polymer have been prepared by stabilising metal nanoparticle aggregates within dry hydroxyethylcellulose (HEC) films. In these films the aggregates are protected by the polymer matrix during storage but in use they are released when aqueous analyte droplets cause the films to swell to their gel form. The fact that these "Poly-SERS" films can be prepared in bulk but then cut to size and stored in air before use means that they provide a cost effective and convenient method for routine SERS analysis. Here we have tested both Ag and Au Poly-SERS films for use in point-of-care monitoring of therapeutic drugs, using phenytoin as the test compound. Phenytoin in water could readily be detected using Ag Poly-SERS films but dissolving the compound in phosphate buffered saline (PBS) to mimic body fluid samples caused loss of the drug signal due to competition for metal surface sites from Cl^- ions in the buffer solution. However, with Au Poly-SERS films there was no detectable interference from Cl^- and these materials allowed phenytoin to be detected at 1.8 mg L^-1, even in PBS. The target range of detection of phenytoin in therapeutic drug monitoring is 10-20 mg L^-1. With the Au Poly-SERS films, the absolute signal generated by a given concentration of phenytoin was lower for the films than for the parent colloid but the SERS signals were still high enough to be used for therapeutic monitoring, so the cost in sensitivity for moving from simple aqueous colloids to films is not so large that it outweighs the advantages which the films bring for practical applications, in particular their ease of use and long shelf life.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes

Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood-retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA2 inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA2 inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA2 may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents.