pH dependence of the progression in NMR T-2 relaxation times in post-mortem muscle

Continuous NMR T-2 relaxation measurements were carried out on seven rabbit longissimus muscle samples in the period from 25 min to 28 h post-mortem at 200 MHz for H-1. To display differences in post-mortern pH progress and extent of changes in water characteristics during conversion of muscle to meat, three of the seven animals were pre-slaughter injected with adrenaline (0.5 mg/kg live weight 4 h before sacrifice) to differentiate muscle glycogen stores at the time of slaughter. Distributed analysis of T-2 data displayed clear differences in the characteristics of the various transverse relaxation components dependent on progress in pH, as did the water-holding capacity of samples 24 h postmortem. This reveals a pronounced effect of the progressive change in pH on the subsequent development in physical/chemical states of water during the conversion of muscle to meat. Finally, the relaxation characteristics are discussed in relation to supposed post-mortem processes of protein denaturation.

Reproducibility of the cycling time to exhaustion at VO(2)peak in highly trained cyclists

The purpose of the present study was to examine, in highly trained cyclists, the reproducibility of cycling time to exhaustion (T-max) at the power output equal to that attained at peak oxygen uptake ((V) over dot O(2)peak) during a progressive exercise test. Forty-three highly trained male cyclists (M +/- SD; age = 25 +/- 6yrs; weight = 75 +/- 7 kg; (V) over dot(2)peak = 64.8 +/- 5.2 ml.kg(-1) . min(-1)) performed two T-max tests one week apart. While the two measures of T-max were strongly related (r = 0.884; p < 0.001), T-max from the second test (245 +/- 57 s) was significantly higher than that of the first (237 +/- 57 s; p = 0.047; two-tailed). Within-subject variability in the present study was calculated to be 6 +/- 6%, which was lower than that previously reported for Tmax in sub-elite runners (25%). The mean T-max was significantly (p < 0.05) related to both the second ventilatory turnpoint (VT2; r = 0.38) and to (V) over dot O(2)peak (r = 0.34). Despite a relatively low within-subject coefficient of variation, these data demonstrate that the second score in a series of two T-max tests may be significantly greater than the first. Moreover the present data show that T-max in highly trained cyclists is moderately related to VT2 and (V) over dot O(2)peak.

BEYOND SAMUELSON`S CHAPTER ON RAMSEY

Paul Anthony Samuelson proposed and practiced a program for the Whig history of economics. One such example is his account of Frank Ramsey`s contribution to optimal taxation in 1927. For him, and mainly for the public finance economists who rediscovered later Ramsey`s contribution, Ramsey was a genius ahead of his time who used a mathematics too advanced for his contemporaries and was thus rediscovered only in the 1970S, when economists became more mathematically literate. In such rediscovery, a memorandum that Samuelsom wrote in 1951 for the us Treasury became central. I examine Samuelson`s account and challenge it in some respects and explore the historical context of the emergence of the optimal taxation literature in the 1970S. Additional, I analyze the canonization of Ramsey in this field, stressing Samuelson`s role in this process as a professor who liked telling stories about economists, especially about Ramsey, to his graduate students.

Modulation of cytochrome P450 monooxygenase by cadmium chloride in the mouse liver: Involvement of transcription factor Nrf2.

Modulation of the cytochrome P450 (CYP) monooxygenase system and haem oxygenase by cadmium was investigated in male, adult DBA/2J mice treated with a single dose (16 Amol/kg body weight, i.p.) of cadmium chloride (CdCl2), at various time points. Total CYP content of liver microsomes decreased significantly (P < 0.05) at 12, 18, and 24 hours (22%, 47%, and 56%, respectively) after treatment. In contrast, progressive increases of hepatic coumarin 7-hydroxylase (COH) activity (indicative of CYP2A5 activity) were observed at 8 hrs (2-fold), 12 hrs (3-fold), and 7-fold at 18 and 24 hrs. Simultaneously, haem oxygenase activity increased significantly at 4 hours and continued to increase progressively to more than 50-fold compared to control. Liver CYP2A5 mRNA levels increased maximally 12 hours after treatment and decreased to almost half 6 hours later, while western blot analysis showed 2- and 3- fold increase in CYP2A5 apoprotein at 12 and 24 hours. The CYP2A5 mRNA levels in the liver increased after Cd treatment in Nrf2 +/+ but not in Nrf2 / mouse. This study demonstrates that hepatic haem oxygenase and CYP2A5 are upregulated by cadmium. The upregulation of haem oxygenase precedes that of CYP2A5. The strong upregulation of the CYP2A5 both at mRNA and enzyme activity levels, with a simultaneous decrease in the total CYP concentration suggest an unusual mode of regulation of CYP2A5 in response to cadmium exposure, amongst the CYP enzymes. The observed increase in the mRNA but not in protein levels after maximal induction may suggest involvement of post-transcriptional mechanisms in the regulation. Upregulation of CYP2A5 by cadmium in the Nrf2 +/+ mice but not in the Nrf2 / mice indicates a role for this transcription factor in the regulation.

Visualization of drip channels in meat using NMR microimaging

The progressive changes in the water distribution within rabbit muscles were studied by nuclear magnetic resonance microscopy during the first 24 h postmortem. T-2 images revealed development of interspersed lines with higher signal intensities in the muscle, reflecting formation of channels containing mobile water. The appearance of the interspersed lines progressed throughout the measuring period and became increasingly evident. After about 3 h postmortem the signal intensity also increased in areas near the surface of the samples, which reflects migration of the mobile water to the sample surface. Proton density images showed the presence of a chemical shift artifact in the interspersed lines, implying that the intrinsic development of water channels progressed in close proximity to the connective tissue. (C) 2004 Elsevier Ltd. All rights reserved.

Dibucaine effects on structural and elastic properties of lipid bilayers

In this work we report the interaction effects of the local anesthetic dibucaine (DBC) with lipid patches in model membranes by Atomic Force Microscopy (AFM). Supported lipid bilayers (egg phosphatidylcholine, EPC and dimyristoylphosphatidylcholine, DMPQ were prepared by fusion of unilamellar vesicles on mica and imaged in aqueous media. The AFM images show irregularly distributed and sized EPC patches on mica. On the other hand DMPC formation presents extensive bilayer regions on top of which multibilayer patches are formed. In the presence of DBC we observed a progressive disruption of these patches, but for DMPC bilayers this process occurred more slowly than for EPC. In both cases, phase images show the formation of small structures on the bilayer surface suggesting an effect on the elastic properties of the bilayers when DBC is present. Dynamic surface tension and dilatational surface elasticity measurements of EPC and DMPC monolayers in the presence of DBC by the pendant drop technique were also performed, in order to elucidate these results. The curve of lipid monolayer elasticity versus DBC concentration, for both EPC and DMPC cases, shows a maximum for the surface elasticity modulus at the same concentration where we observed the disruption of the bilayer by AFM. Our results suggest that changes in the local curvature of the bilayer induced by DBC could explain the anesthetic action in membranes. (C) 2008 Elsevier B.V. All rights reserved.

Preparation, characterization and catalytic studies of V2O5-SiO2 xerogel composite

In this work, we report the synthesis, characterization and catalytic properties of a vanadium oxide-silicon oxide composite xerogel prepared by a soft chemistry approach. In order to obtain such material, we submitted a vanadium pentoxide gel previously synthesized via protonation of metavanadate species to an ""in situ"" progressive polycondensation into silica gel. The material has been characterized by X-ray diffraction, infrared spectroscopy, thermogravimetric analysis and scanning electron microscopy. Further, the catalytic activity of this material was evaluated for the epoxidation of styrene and cyclooctene using iodosylbenzene, hydrogen peroxide and m-chloroperbenzoic acid as the oxidizing agent.

Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for the treatment of schizophrenia and related disorders

Background: The Royal Australian and New Zealand College of Psychiatrists is co-ordinating the development of clinical practice guidelines (CPGs) in psychiatry, funded under the National Mental Health Strategy (Australia) and the New Zealand Health Funding Authority. This paper presents CPGs for schizophrenia and related disorders. Over the past decade schizophrenia has become more treatable than ever before. A new generation of drug therapies, a renaissance of psychological and psychosocial interventions and a first generation of reform within the specialist mental health system have combined to create an evidence-based climate of realistic optimism. Progressive neuroscientific advances hold out the strong possibility of more definitive biological treatments in the near future. However, this improved potential for better outcomes and quality of life for people with schizophrenia has not been translated into reality in Australia. The efficacy-effectiveness gap is wider for schizophrenia than any other serious medical disorder. Therapeutic nihilism, under-resourcing of services and a stalling of the service reform process, poor morale within specialist mental health services, a lack of broad-based recovery and life support programs, and a climate of tenacious stigma and consequent lack of concern for people with schizophrenia are the contributory causes for this failure to effectively treat. These guidelines therefore tackle only one element in the endeavour to reduce the impact of schizophrenia. They distil the current evidence-base and make recommendations based on the best available knowledge. Method: A comprehensive literature review (1990-2003) was conducted, including all Cochrane schizophrenia reviews and all relevant meta-analyses, and a number of recent international clinical practice guidelines were consulted. A series of drafts were refined by the expert committee and enhanced through a bi-national consultation process. Treatment recommendations: This guideline provides evidence-based recommendations for the management of schizophrenia by treatment type and by phase of illness. The essential features of the guidelines are: (i) Early detection and comprehensive treatment of first episode cases is a priority since the psychosocial and possibly the biological impact of illness can be minimized and outcome improved. An optimistic attitude on the part of health professionals is an essential ingredient from the outset and across all phases of illness. (ii) Comprehensive and sustained intervention should be assured during the initial 3-5 years following diagnosis since course of illness is strongly influenced by what occurs in this 'critical period'. Patients should not have to 'prove chronicity' before they gain consistent access and tenure to specialist mental health services. (iii) Antipsychotic medication is the cornerstone of treatment. These medicines have improved in quality and tolerability, yet should be used cautiously and in a more targeted manner than in the past. The treatment of choice for most patients is now the novel antipsychotic medications because of their superior tolerability and, in particular, the reduced risk of tardive dyskinesia. This is particularly so for the first episode patient where, due to superior tolerability, novel agents are the first, second and third line choice. These novel agents are nevertheless associated with potentially serious medium to long-term side-effects of their own for which patients must be carefully monitored. Conventional antipsychotic medications in low dosage may still have a role in a small proportion of patients, where there has been full remission and good tolerability; however, the indications are shrinking progressively. These principles are now accepted in most developed countries. (vi) Clozapine should be used early in the course, as soon as treatment resistance to at least two antipsychotics has been demonstrated. This usually means incomplete remission of positive symptomatology, but clozapine may also be considered where there are pervasive negative symptoms or significant or persistent suicidal risk is present. (v) Comprehensive psychosocial interventions should be routinely available to all patients and their families, and provided by appropriately trained mental health professionals with time to devote to the task. This includes family interventions, cognitive-behaviour therapy, vocational rehabilitation and other forms of therapy, especially for comorbid conditions, such as substance abuse, depression and anxiety. (vi) The social and cultural environment of people with schizophrenia is an essential arena for intervention. Adequate shelter, financial security, access to meaningful social roles and availability of social support are essential components of recovery and quality of life. (vii) Interventions should be carefully tailored to phase and stage of illness, and to gender and cultural background. (viii) Genuine involvement of consumers and relatives in service development and provision should be standard. (ix) Maintenance of good physical health and prevention and early treatment of serious medical illness has been seriously neglected in the management of schizophrenia, and results in premature death and widespread morbidity. Quality of medical care for people with schizophrenia should be equivalent to the general community standard. (x) General practitioners (GPs)s should always be closely involved in the care of people with schizophrenia. However, this should be truly shared care, and sole care by a GP with minimal or no special Optimal treatment of schizophrenia requires a multidisciplinary team approach with a consultant psychiatrist centrally involved.

What is an effective health consumer? A convergent interviewing approach

This study is part of a larger project on the measurement of effective health consumers in the context of musculoskeletal illness. This complex issue involves the progressive nature of the disease, invisibility of the illness and attendant impairments, complexity of decision-making and negotiation, and urgent need to translate emergent evidence about treatment and management to patients and health professionals. We conducted indepth interviews with patients, family members, general practitioners, specialist clinicians, and health consumer advocates (N = 84) about effective consumers in this context, using a process of convergent interviewing, with convergence conducted within and across groups and countries. The initial set of themes included information seeking and adaptation, decision-making, roles of patients, GPs, and specialists and communication between them, importance of pain and impact of depression, impact of the social environment (including the invisibility of the disease and the need for a normal life), and coping strategies.

A new clinical and molecular form of Unverricht-Lundborg disease localized by homozygosity mapping

Progressive myoclonus epilepsy (PME) has a number of causes, of which Unverricht-Lundborg disease (ULD) is the most common. ULD has previously been mapped to a locus on chromosome 21 (EPM1). Subsequently, mutations in the cystatin B gene have been found in most cases. In the present work we identified an inbred Arab family with a clinical pattern compatible with ULD, but mutations in the cystatin B gene were absent. We sought to characterize the clinical and molecular features of the disorder. The family was studied by multiple field trips to their town to clarify details of the complex consanguineous relationships and to personally examine the family. DNA was collected for subsequent molecular analyses from 21 individuals. A genome-wide screen was performed using 811 microsatellite markers. Homozygosity mapping was used to identify loci of interest. There were eight affected individuals. Clinical onset was at 7.3 +/- 1.5 years with myoclonic or tonic-clonic seizures. All had myoclonus that progressed in severity over time and seven had tonic-clonic seizures. Ataxia, in addition to myoclonus, occurred in all. Detailed cognitive assessment was not possible, but there was no significant progressive dementia. There was intrafamily variation in severity; three required wheelchairs in adult life; the others could walk unaided. MRI, muscle and skin biopsies on one individual were unremarkable. We mapped the family to a 15-megabase region at the pericentromeric region of chromosome 12 with a maximum lod score of 6.32. Although the phenotype of individual subjects was typical of ULD, the mean age of onset (7.3 years versus 11 years for ULD) was younger. The locus on chromosome 12 does not contain genes for any other form of PME, nor does it have genes known to be related to cystatin B. This represents a new form of PME and we have designated the locus as EPM1B.

Destiny and will, religion and politics: Jesus Society and Enlightenment in the posthumous Malabar Rites controversy

The first presentation of Antoine-Marin Le Mierre`s tragedy Malabar Widow, or the Empire of Customs, took place in 1770. It was based on the famous controversy over the Malabar (south west India) Rites. The object of the controversy was the Jesuit project in India, which started in the beginning of XVII century and was stopped by the Pope Benedict XIV, with the Apostolic Constitution Omnium Sollicitudinum. The papal condemnation of the rites closed a long process which shows the progressive loss of power of the Jesuit Company in the Age of Enlightenment, which will be definitive in 1773, with the suppression of the Company. In Le Mierre`s tragedy, we find the judgment of Malabar rites according to the rationalist ideas of the Enlightenment, with some typical topoi of the philosophes`s cultural perspective. At the same time, the enlightened disputation reproduces the Jesuit internal debate about India itself. Starting from a religious universal perspective of the different strategies of Christianization in India, or in the entire East, the missionary controversy had been about the religious or political interpretation of local signs. Briefly, this polemic would turn into the controversy on the rites. The criticism to the Jesuitical strategy of mission, in XVII and XVIII centuries, would start from here. The enormous number of documents on this issue became a powerful instrument in the battle against the Jesuits, in the XVIII century. On the base of the missionary disputation, the Enlightenment constructs the proposal of a new political and humanistic universal perspective. According to this, eventuality, the religion becomes just a privileged instrument to realize this operation.

Prognostic Significance of Myocardial Fibrosis Quantification by Histopathology and Magnetic Resonance Imaging in Patients With Severe Aortic Valve Disease

Objectives We sought to determine whether the quantitative assessment of myocardial fibrosis (MF), either by histopathology or by contrast-enhanced magnetic resonance imaging (ce-MRI), could help predict long-term survival after aortic valve replacement. Background Severe aortic valve disease is characterized by progressive accumulation of interstitial MF. Methods Fifty-four patients scheduled to undergo aortic valve replacement were examined by ce-MRI. Delayed-enhanced images were used for the quantitative assessment of MF. In addition, interstitial MF was quantified by histological analysis of myocardial samples obtained during open-heart surgery and stained with picrosirius red. The ce-MRI study was repeated 27 +/- 22 months after surgery to assess left ventricular functional improvement, and all patients were followed for 52 +/- 17 months to evaluate long-term survival. Results There was a good correlation between the amount of MF measured by histopathology and by ce-MRI (r = 0.69, p < 0.001). In addition, the amount of MF demonstrated a significant inverse correlation with the degree of left ventricular functional improvement after surgery (r = -0.42, p = 0.04 for histopathology; r = -0.47, p = 0.02 for ce-MRI). Kaplan-Meier analyses revealed that higher degrees of MF accumulation were associated with worse long-term survival (chi-square = 6.32, p = 0.01 for histopathology; chi-square = 5.85, p = 0.02 for ce-MRI). On multivariate Cox regression analyses, patient age and the amount of MF were found to be independent predictors of all-cause mortality. Conclusions The amount of MF, either by histopathology or by ce-MRI, is associated with the degree of left ventricular functional improvement and all-cause mortality late after aortic valve replacement in patients with severe aortic valve disease. (J Am Coll Cardiol 2010; 56: 278-87) (c) 2010 by the American College of Cardiology Foundation

Tyrosine hydroxylase deficiency: a treatable disorder of brain catecholamine biosynthesis

Tyrosine hydroxylase deficiency is an autosomal recessive disorder resulting from cerebral catecholamine deficiency. Tyrosine hydroxylase deficiency has been reported in fewer than 40 patients worldwide. To recapitulate all available evidence on clinical phenotypes and rational diagnostic and therapeutic approaches for this devastating, but treatable, neurometabolic disorder, we studied 36 patients with tyrosine hydroxylase deficiency and reviewed the literature. Based on the presenting neurological features, tyrosine hydroxylase deficiency can be divided in two phenotypes: an infantile onset, progressive, hypokinetic-rigid syndrome with dystonia (type A), and a complex encephalopathy with neonatal onset (type B). Decreased cerebrospinal fluid concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylethylene glycol, with normal 5-hydroxyindoleacetic acid cerebrospinal fluid concentrations, are the biochemical hallmark of tyrosine hydroxylase deficiency. The homovanillic acid concentrations and homovanillic acid/5-hydroxyindoleacetic acid ratio in cerebrospinal fluid correlate with the severity of the phenotype. Tyrosine hydroxylase deficiency is almost exclusively caused by missense mutations in the TH gene and its promoter region, suggesting that mutations with more deleterious effects on the protein are incompatible with life. Genotype-phenotype correlations do not exist for the common c.698G > A and c.707T > C mutations. Carriership of at least one promotor mutation, however, apparently predicts type A tyrosine hydroxylase deficiency. Most patients with tyrosine hydroxylase deficiency can be successfully treated with l-dopa.

Charcot`s arthropathy secondary to herpetic encephalitis sequelae: an unusual presentation

Neuropathic arthropathy (Charcot`s arthropathy) is a progressive articular disease associated with a reduced sensorial and protector proprioceptive reflex. Its etiology includes many different conditions such as syringomyelia, traumatic lesion causing medullary deformity, spina bifida, diabetic neuropathy, leprosy neuropathy, neurofibromatosis, amyloid neuropathy, alcohol, and repetitive injection of hydrocortisone into joints, among others. However, the relationship between Charcot`s arthropathy and herpetic encephalitis has not yet been described. Herpes encephalitis causes acute and chronic diseases of the peripheral or central nervous system. It can manifest as subacute encephalitis, recurrent meningitis, or myelitis. It can also resemble psychiatric syndromes, diplopia, sensory changes in the face and limbs, personality changes, frontal dysexecutive syndrome, stiff neck, subclinical alterations of the vestibular function, intracranial hypertension, convulsion, hemiparesis, and generally includes motor components, among others. On the other hand, pure peripheral sensory disturbance has not been described. In this article, we report the clinical case of a patient with Charcot`s arthropathy secondary to pure peripheral sensory polyneuropathy as a consequence of progressive herpetic encephalitis sequelae. In this article, the authors report the first case of Charcot`s arthropathy secondary to herpetic encephalitis.

Chronic Recurrent Multifocal Osteomyelitis Primarily Affecting the Spine Treated With Anti-TNF Therapy

Study Design. A case report describing chronic recurrent multifocal osteomyelitis (CRMO) with initial presentation limited to spine, successfully treated by anti-TNF-alpha therapy after failure of conventional treatment methods. Objective. To describe an unusual manifestation and treatment of a rare disease. Summary of Background Data. CRMO is a rare inflammatory bone disease that should be differentiated from bacterial osteomyelitis. Rarely, it can affect the spine and in this case the most important differential diagnosis is infectious spondylodiscitis. The disease has an unpredictable course with exacerbations and spontaneous remissions. Although the majority of cases remit spontaneously (or after the use of nonsteroidal anti-inflammatory drugs [NSAIDs]), some progressive and resistant cases have been reported. Methods. We describe a case of CRMO with an unusual clinical presentation emphasizing the importance of this finding as a differential diagnosis of spondylodiscitis and comment on the available treatment alternatives. Results. A 17-year-old man presented with debilitating dorsal spine pain. Magnetic resonance imaging of the spine revealed bone lesions at multiple vertebral levels. After failure of antibiotic treatment, the diagnosis of CRMO was suggested. An initial good response to NSAIDs was followed by a recurrent course and involvement of peripheral joints besides the use of corticosteroids and other drugs. The introduction of infliximab was followed by complete remission of the disease. Conclusion. Our observation highlights the need of awareness for the differential diagnosis in suspected cases of osteomyelitis not responding to antibiotics. Anti-TNF-alpha agents should be considered in CRMO refractory cases.