Ischemic preconditioning: triggering role of nitric oxide-derived oxidants in isolated hearts

There is evidence that oxidants generated during ischemic preconditioning (IPC) trigger or mediate cardioprotection. We examined whether a causal relationship exists between oxidant formation during ischemic preconditioning and cardioprotection. We monitored formation of dityrosine in crystalloid-perfused guinea pig isolated hearts after a preconditioning protocol and after prolonged ischemia. Superoxide dismutase, catalase, and glutathione (SCG), or the L-arginine analogue NGnitro L-arginine methyl ester (L-NAME) were given during preconditioning. Dityrosine was observed in the coronary effluent immediately after both stimuli, but not after bracketing with SCG or L-NAME. After prolonged ischemia, dityrosine was significantly lower in the IPC group than in other groups. IPC was evidenced by improved mechanical and metabolic function on reperfusion, and by reduced infarction. These effects were abrogated by either SCG or L-NAME. These data support the hypothesis that the formation of nitric oxide-derived oxidants during ischemic preconditioning is causally related to myocardial adaptation to reperfusion injury.     

Anesthetic preconditioning: effects on latency to ischemic injury in isolated hearts

BACKGROUND: Anesthetic preconditioning (APC) is protective for several aspects of cardiac function and structure, including left ventricular pressure, coronary flow, and infarction. APC may be protective, however, only if the duration of ischemia is within a certain, as yet undefined range. Brief ischemia causes minimal injury, and APC would be expected to provide little benefit. Conversely, very prolonged ischemia would ultimately cause serious injury with or without APC. Previous investigations used a constant ischemic time as the independent variable to assess ischemia-induced changes in dependent functional and structural variables. The purpose of the study was to define the critical limits of efficacy of APC by varying ischemic time. METHODS: Guinea pig hearts (Langendorff preparation; n = 96) underwent pretreatment with sevoflurane (APC) or no treatment (control), before global ischemia and 120 min reperfusion. Ischemia durations were 20, 25, 30, 35, 40, and 45 min. RESULTS: At 120 min reperfusion, developed (systolic-diastolic) left ventricular pressure was increased by APC compared with control for ischemia durations of 25-40 min. Infarction was decreased by APC for ischemia durations of 25-40 min, but not 20 or 45 min. APC improved coronary flow and vasodilator responses for all ischemia durations longer than 25 min, and decreased ventricular fibrillation on reperfusion for ischemia durations longer than 30 min. CONCLUSIONS: Although APC protects against vascular dysfunction and dysrhythmias after prolonged ischemia, protection against contractile dysfunction and infarction in this model is restricted to a range of ischemia durations of 25-40 min. These results suggest that APC may be effective in a subset of patients who have cardiac ischemia of intermediate duration.     

The global campaign against epilepsy in Africa

One of the leading brain disorders in developing countries is represented by epilepsy. It is estimated that 80% of people suffering from epilepsy around the world, reside in developing world such as Africa. Many perinatal and postnatal causes are brain-stressers in people suffering from malnutrition and low economical conditions. This context is characterised by long delay before modern treatment, reduced number and financial inaccessibility to anti-epileptic drugs (AEDs) and limited human and technical resources for epilepsy. Cultural interpretation also contributes to exclude epileptic patients from the educational and productive fields, aggravating the burden they face and favouring a treatment gap estimated to 80%. To fight against this dramatic reality, a partnership has been built between the International League against Epilepsy, the International Bureau for Epilepsy and the World Health Organisation, named the "Global Campaign Against Epilepsy" "Epilepsy Out of the Shadows" to reduce treatment gap and social and physical burden, educate health personnel, dispel stigma, support prevention.     

Evaluating and developing contraceptive services: the results of an audit of the North Lambeth Primary Care Commissioning Group

Primary care groups are expected to meet the primary health care needs of their local population. In the inner-city London borough of Lambeth there are high levels of sexual health needs. The North Lambeth Primary Care Commissioning Group identified the evaluation and further development of contraceptive services, particularly to those under the age of 25, as a priority. An evaluation of current contraceptive service provision from general practice was carried out. The evaluation covered contraceptive service factors identified from the literature as linked to effective, acceptable, accessible and equitable service delivery. Factors linked to the effectiveness of services included service use, information provision, training of staff, provision of the full range of methods and services. Factors linked to the acceptability of services included confidentiality and the choice of the gender of the provider. The strengths and limitations of the data and indicators used are outlined. Areas requiring further evaluation are highlighted. The evaluation indicated scope for service development in all the key areas evaluated, and illustrated examples of good practice. For example, whilst information in practice leaflets and surgery waiting areas about the contraceptive services available was generally limited, one practice provided excellent information. Recommendations for service development were made covering information provision, staff training, and confidential access to services. These are being taken forward by an ongoing project.     

The natural history of chronic actinic dermatitis

OBJECTIVE: To determine the prognosis for resolution of abnormal cutaneous photosensitivity in patients with chronic actinic dermatitis (also known as the photosensitivity dermatitis and actinic reticuloid syndrome). DESIGN: Historical cohort study involving follow-up of patients for up to 24 years from diagnosis. SETTING: A Scottish tertiary referral center for investigation of photodermatosis. PATIENTS: One hundred seventy-eight patients with chronic actinic dermatitis, 62% of a cohort of 285 living patients identified in the Photobiology Unit database. INTERVENTIONS: Recall for repeated clinical assessment and monochromator phototesting. All patients underwent patch testing when initially assessed; this was repeated at follow-up in a subgroup of patients. MAIN OUTCOME MEASURES: Resolution of abnormal photosensitivity, defined as clinical resolution and return of phototest responses to within normal population limits. In addition, possible prognostic factors for resolution of photosensitivity were examined. RESULTS: The probability of abnormal photosensitivity resolving by 10 years from diagnosis is 1 in 5. Particularly severe abnormal UV-B photosensitivity (minimal erythema dose at 305+/-5 nm half-maximum bandwidth, < or =5.6 mJ x cm(-2)) and the identification of separate contact allergens in 2 or more patch test batteries are predictors of a poorer prognosis for resolution. Loss of contact allergies was not associated with a different prognosis for photosensitivity resolution. Our findings probably underestimate the probability of resolution, as those referred to a tertiary referral center and willing to attend for follow-up may include a disproportionate number of severely affected patients. CONCLUSIONS: Newly diagnosed patients can be told that most of them will improve with appropriate UV/visible light and allergen avoidance and that there is hope that their photosensitivity will completely resolve.     

Binding of uptake blockers to the neuronal dopamine transporter: further investigation about cationic and anionic requirements

Effects of ions on the binding of uptake blockers to the rat dopamine transporter (rDAT) labelled with [3H]WIN 35,428 [2beta-carbomethoxy-3beta-(4-fluorophenyl)-[3H] tropane] and [3H]mazindol were studied at 20 degrees C. [3H]WIN 35,428 binding increased with Na+ concentrations of up to 10-60 mM and decreased at higher concentrations. At pH 7.4, incubation media containing NaCl and/or Na2HPO4/NaH2PO4 were less stimulant than an NaHCO3/NaH2PO4 medium and they shifted maximal binding values to higher ionic concentrations. In an NaHCO3/NaH2PO4-buffered medium, Na+ concentrations >10 mM decreased the binding of 0.2 nM [3H]WIN 35,428, but an increase of the radioligand concentration shifted this decrease to the right. [3H]Mazindol binding was stimulated by Na+ concentrations < or =10 mM and was rather unaffected at higher concentrations. The inhibition of [3H]WIN 35,428 binding produced by 130 mM Na+ was independent of the nature of the anion; in contrast, isothionate and H2PO4-/HCO3 produced a more pronounced inhibition of the [3H]mazindol binding than Cl- and Br-, whereas I- tended to be a stimulant. Ca2+ and Mg2+ more potently inhibited the [3H]WIN 35,428 binding than K+. All these cations recognize a site which is not mutually exclusive with that of the radioligand since they induced the dissociation of the [3H]WIN 35,428-rDAT complex, an effect which was reduced (K+) or modified (Ca2+) when the Na+ concentration was increased. This site is likely to be the Na+ site by which low Na+ concentrations allosterically stimulate the uptake blocker binding. However, the intensity of the cation-induced dissociations was moderate and the main component of the binding inhibition that these cations produced results from the occupancy of a cation site, mutually exclusive with that of the radioligand. Thus, the WIN 35,428 binding inhibition produced by Ca2+, K+ and Na+ was competitive, and Na+ reduced the inhibitory potency of Ca2+ and K+. This reduction was more intense for Ca2+ and Mg2+ than for K+, suggesting that occupancy of the cation site by a divalent cation activated a strong negative allosteric interaction between this site and the Na+ site. Decrease in the Na+ concentration from 10 mM to 5 mM, or replacement of 5 mM HCO3-/H2PO4- by an equimolar concentration of isethionate or Cl- did not modify [3H]WIN 35,428 binding dissociation. Level(s) at which anions stimulate and inhibit the binding of uptake blockers remain uncertain and could be specific for each radioligand.     

An examination of the utility of the AUDIT in people with schizophrenia

OBJECTIVE: To examine the reliability and validity of the Alcohol Use Disorders Identification Test (AUDIT) compared to a structured diagnostic interview, the Composite International Diagnostic Interview (CIDI; 12-month version) in psychiatric patients with a diagnosis of schizophrenia. METHOD: Patients (N = 71, 53 men) were interviewed using the CIDI (Alcohol Misuse Section; 12-month version) and then completed the AUDIT. RESULTS: The CIDI identified 32.4% of the sample as having an alcohol use disorder. Of these, 5 (7.0%) met diagnostic criteria for harmful use of alcohol, 1 (1.4%) met diagnostic criteria for alcohol abuse and 17 (23.9%) met diagnostic criteria for alcohol dependence. The AUDIT was found to have good internal reliability (coefficient = 0.85). An AUDIT cutoff of > or = 8 had a sensitivity of 87% and specificity of 90% in detecting CIDI-diagnosed alcohol disorders. All items except Item 9 contributed significantly to discriminant validity. CONCLUSIONS: The findings replicate and extend previous findings of high rates of alcohol use disorders in people with severe mental illness. The AUDIT was found to be reliable and valid in this sample and can be used with confidence as a screening instrument for alcohol use disorders in people with schizophrenia.     

SAKM: self-adaptive kernel machine. A kernel-based algorithm for online clustering

This paper presents a new online clustering algorithm called SAKM (Self-Adaptive Kernel Machine) which is developed to learn continuously evolving clusters from non-stationary data. Based on SVM and kernel methods, the SAKM algorithm uses a fast adaptive learning procedure to take into account variations over time. Dedicated to online clustering in a multi-class environment, the algorithm designs an unsupervised neural architecture with self-adaptive abilities. Based on a specific kernel-induced similarity measure, the SAKM learning procedures consist of four main stages: Creation, Adaptation, Fusion and Elimination. In addition to these properties, the SAKM algorithm is attractive to be computationally efficient in online learning of real-drifting targets. After a theoretical study of the error convergence bound of the SAKM local learning, a comparison with NORMA and ALMA algorithms is made. In the end, some experiments conducted on simulation data, UCI benchmarks and real data are given to illustrate the capacities of the SAKM algorithm for online clustering in non-stationary and multi-class environment.