In vitro and in vivo Evaluation of a Factor VIII Concentrate Heat-Treated to Inactivate HTLV-III/LAV Viruses

We report here the results of our evaluation of the effects of a dry heat treatment (96 h at 68 degrees C) to eliminate LAV/HTLV-III virus on factor VIII (FVIII) and von Willebrand factor (vWf) present in an intermediate-purity concentrate. This thermal inactivation appears to have little effect on FVIII. There is an acceptable loss (12.3 +/- 3.6%; n = 25) in FVIII coagulant activity (FVIII: C) and a good in vivo performance in haemophilia A patients. A precise analysis of vWf indicates that whereas the vWf antigen and its ristocetin cofactor activity decrease during heating, there is an increase in potentially functional forms of vWf. Heat treatment induces an increase in high molecular weight forms of vWf and an enhancement in platelet adhesion to collagen. These changes probably explain the correcting effect on the bleeding time of the heated FVIII concentrate in patients with von Willebrand's disease. Thus, this heat-treated concentrate appears to be equivalent to the untreated product in haemophilia A, with the additional benefit of being efficient for the treatment of von Willebrand's disease.     

The Beagle Dog as an Animal Model for a Bioavailability Study of Controlled-Release Theophylline Under the Influence of Food

Beagle dogs were evaluated as an animal model to study the effect of food on the bioavailability of two commercially available oral controlled-release theophylline products. The products were administered with and without food in single doses, and the bioavailability parameters were compared with those following an i.v. aminophylline dose. The total plasma theophylline clearance in dogs following an i.v. dose was 0.128 liter/hr/kg and the volume of distribution was 0.8 liter/kg using a one-compartment model. The absolute bioavailabilities of these two products under fasting conditions were 31 and 48%, respectively. The food increased the bioavailability of one product and decreased the bioavailability of the other. The overall trends in relative bioavailability of these two products with and without food appeared to be similar to those reported in humans.     

Respiratory evoked potentials and occlusion elicited sympathetic skin response.

INTRODUCTION: Neurophysiological study of respiratory structures usually relies upon diaphragm electromyography and phrenic nerve conduction study, which do not assess the afferent sensory pathways. OBJECTIVE: To assess the feasibility of respiratory evoked potentials (REPs) and sympathetic skin responses (SSRs) elicited by inspiratory occlusion. METHODS: REPs and SSRs were studied in 12 healthy adults. REPs were elicited by inspiratory occlusions triggered by the physician within 1 s after the onset of a respiratory effort. They were recorded from C3, C4 and Cz needle electrodes (referenced to Fz). Each individual trial consisted of two superimposed 30-sweep averaged responses to inspiratory occlusions. SSRs were recorded from surface electrodes placed on the subject's hand and elicited by similar inspiratory occlusions. RESULTS: Reproducible REPs and SSRs were obtained in all subjects. Mean latencies of initial P1 and N1 cortical responses were 41 and 72 ms, respectively. SSRs were similar to those usually elicited by peripheral nerve electrical stimulation. CONCLUSION: Brief occlusion of inspiration induces cortical and sympathetic activation, both are easily recordable. Since REPs are considered to be the neurophysiological substrate of certain types of respiratory sensations and are altered in different chronic respiratory diseases, they, in addition to SSR, represent attractive new techniques that may provide better understanding of respiratory dysfunction.     

Bioinformatics: The philosophical and ethical issues at stake in a new modality of research practices

This article deals with the integration of ethical reflection into the research practices of the project at the Lille Nord-Pas-de-Calais genopole: “Multifactorial genetic pathologies and therapeutic innovations”. The general hypothesis of this text is that changes in research practices in biology (mainly through the use of bioinformatics) imply changes in medical practices, which require critical reflection. This hypothesis could be broken down into three sub-hypotheses: (1) Research in biology is undergoing a complete transformation; (2) Research in biology is a cultural practice, which cannot be reduced to a simple cognitive action; (3) Research in biology is a techno-scientific practice. As for the method, the aim of our research at the Medical Ethics Centre is to elucidate the philosophical and ethical range of biomedical practices. This work entails a double task for reflection. On the one hand, from the revelation of ethical tensions present in these practices, we have to think about what is at stake in these practices, and more broadly in society. On the other hand, we have to analyse the conditions enabling the actors to assume the significance of ethical reflection in their practices. The method set up to undertake this double task could be qualified as “narrative hermeneutics”, as its aim is to attempt to interpret the stakes in practices from proximity with these practices and from what their actors have to say about them. The text then goes on to analyse more specifically the emergence and place of bioinformatics in present-day biomedical research.     

Differentiated rabbit prostatic stromal cells in primary culture display functional alpha1A-adrenoceptors

AIMS: BPH is characterized by uncontrolled proliferation and increased contractility of prostatic smooth muscle cells. The activation of alpha1-adrenoceptors (alpha1-AR) seems involved in the latter event, but the lack of in vitro models expressing these receptors has hampered a more specific characterization of their role. In order to do so, we attempted to develop a new model of rabbit cultured prostatic stromal cells (PSC) in a non-proliferative and differentiated state. METHODS: The expression of cytoskeletal and stromal markers was confirmed by immunohistochemistry on primary cultured PSC. Alpha1-AR subtype expression was assessed by RT-PCR, while receptor coupling to the ERK1/ERK2 and calcium pathways was studied by Western Blot and Fura-2 calcium imaging, respectively. RESULTS: Cells grown under non-proliferative conditions displayed a differentiated phenotype, with expression of contractile cytoskeletal and stromal proteins. Furthermore, the alpha1A-AR was shown to activate ERK1/ERK2 as well as calcium signaling. CONCLUSION: These results emphasize the interest of this model for the characterization of PSC adrenergic regulation, in particular through the little-known alpha1A-AR.     

Antimicrobial activities of the methanol extract and compounds from the twigs of Dorstenia mannii (Moraceae)

Background

Ribosome-inactivating proteins (RIP) have been studied in the search for toxins that could be used as immunotoxins for cancer treatment. Pulchellin, a type 2 RIP, is suggested to induce immune responses that have a role in controlling cancer.

Methods

The percentage of dendritic cells and CD4⁺ and CD8⁺ T cells in the spleen (flow cytometry), cytokines?? release by PECs and splenocytes (ELISA) and nitric oxide production by PECs (Griess assay) were determined from tumor-bearing mice injected intratumorally with 0.1?ml of pulchellin at 0.75???g/kg of body weight. Statistical analysis was performed by one-way ANOVA with Tukey??s post hoc test.

Results

Pulchellin-treated mice showed significant immune system activation, characterized by increased release of IFN-?? and Th2 cytokines (IL-4 and IL-10), while IL-6 and TGF-?? levels were decreased. There was also an increase in macrophage??s activation, as denoted by the higher percentage of macrophages expressing adhesion and costimulatory molecules (CD54 and CD80, respectively).

Conclusions

Our results suggest that pulchellin is promising as an adjuvant in breast cancer treatment.     

Uso de fármacos inmunomoduladores en una consulta de uveítis

ObjectiveThe treatment of noninfectious uveitis includes steroids and immunomodulatory drugs, the use of which has increased in the last few years, and the options have been enriched with the development of new treatments. However, clear therapeutic guidelines and protocols have not been developed. The purpose is to analyze the response to the drugs used and the characteristics of the patients treated at a multidisciplinary uveitis clinic.Material and methodsObservational and retrospective study of the patients attended to from January 2012 to December 2015. Infectious, posttraumatic and postoperative uveitis, as well as masquerade syndrome, were excluded.ResultsTwo hundred six patients were included. Overall, 58.80% had uveitis without association of systemic disease, mostly idiopathic uveitis, and 35.65% had uveitis with systemic involvement, mainly related to spondyloarthritis. Uveitis without systemic association and anterior uveitis achieved disease control with local treatment more frequently than others (p = .002 and p < .001, respectively). In all, 49.76% of the patients required systemic treatment. Among those treated with immunomodulators, 53.26% needed a second drug and 31.52% needed a third drug. Women required immunomodulators more often than men (P = .042). Methotrexate was the most widely used immunomodulator. Posterior uveitis responded less favorably to the second immunomodulator than anterior uveitis (p = .006).ConclusionsAlmost half of the patients needed an immunomodulatory drug and some of them required successive drug changes. Intermediate uveitis was the most treatment-refractory uveitis.