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Long Lasting (long + lasting)
Selected AbstractsLong-term follow-up of achalasic patients treated with botulinum toxinDISEASES OF THE ESOPHAGUS, Issue 2 2000D'Onofrio Botulinum toxin A (BoTx), a potent inhibitor of acetylcholine release from nerve endings both within the myenteric plexus and at the nerve,muscle junction, has been shown to decrease the lower esophageal sphincter (LES) pressure in patients with achalasia. Because of this property, the esophageal injection of BoTx has been suggested as an alternative treatment in achalasia. The objective of this study was to determine the long-term efficacy and safety of intrasphincteric injection of BoTx in a group of achalasic patients. Nineteen patients (mean age 56.1 ± 19.2 years) were enrolled in the study. All of them were injected endoscopically with 100 U of BoTx by sclerotherapy needle at different sites of the LES. Symptom score (dysphagia, regurgitation and chest pain, each on a 0,3 scale), esophageal manometer and esophageal radionuclide emptying were assessed before the treatment and at 4 weeks, 3 months and 1 year after BoTx injection. In case of failure or relapse (symptom score >2), the treatment was repeated. All but five patients (74%) were in clinical remission at 1 month. Mean symptom score after 1 month of BoTx decreased from 7.1 ± 0.9 to 2.2 ± 2.5 (p < 0.05). LES pressure decreased from 38.4 ± 13.7 to 27.4 ± 13.5 mmHg (p < 0.05) and 10-min radionuclide retention decreased from 70.9 ± 20.7% to 33.8 ± 27.0% (p < 0.05). Side-effects (transient chest pain) were mild and infrequent. At 12 months, the clinical score was 0.9 ± 0.5 (p < 0.05 vs. basal); mean LES pressure was 22.0 ± 7.1 (p < 0.05 vs. basal) and 10-min radionuclide retention was 15.8 ± 6.0% (p < 0.05 vs. basal). The efficacy of the first injection of BoTx lasted for a mean period of 9 months (range 2,14 months). At the time of writing (follow-up period mean 17.6 months, range 2,31), 14 patients (10 with one injection) were still in remission (74%). Our results showed that one or two intrasphincteric injections of BoTx resulted in clinical and objective improvement in about 74% of achalasic patients and are not associated with serious adverse effects; the efficacy of BoTx treatment was long lasting; this procedure could be considered an attractive treatment, especially in elderly patients who are poor candidates for more invasive procedures. [source] The Shiga toxin B-subunit targets antigen in vivo to dendritic cells and elicits anti-tumor immunityEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 5 2006Benoit Vingert Abstract The non-toxic B-subunit of Shiga toxin (STxB) interacts with the glycolipid Gb3, which is preferentially expressed on dendritic cells (DC) and B cells. After administration of STxB chemically coupled to OVA (STxB-OVA) in mice, we showed that the immunodominant OVA257,264 peptide restricted by Kb molecules is specifically presented by CD11c+CD8,, DC, some of them displaying a mature phenotype. Using mice carrying a transgene encoding a diphtheria toxin receptor (DTR) under the control of the murine CD11c promoter, which allows inducible ablation of DC, we showed that DC are required for efficient priming of CTL after STxB-OVA vaccination. Immunization of mice with STxB-OVA induced OVA-specific CD8+ T cells detected ex vivo; these cells were long lasting, since they could be detected even 91,days after the last immunization and were composed of both central and memory T cells. Vaccination of mice with STxB-OVA and STxB coupled to E7, a protein derived from HPV16, inhibited tumor growth in prophylactic and therapeutic experiments. This effect was mainly mediated by CD8+ T cells. STxB therefore appears to be a powerful carrier directly targeting DC in vivo, resulting in a strong and durable CTL response associated with tumor protection. [source] Vaccination with myelin oligodendrocyte glycoprotein adsorbed to alum effectively protects DBA/1 mice from experimental autoimmune encephalomyelitisEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 6 2003Maja Wållberg Abstract To prevent an organism from developing autoimmunity the body limits the number of autoreactive cells through thymic negative selection and regulates their activity through induction of suppressor T cells. Development of antigen-specific therapies provides an interesting opportunity to imitate the body's own, often effective, method of protection. Our study demonstrates that DBA/1 mice could be protected from experimental autoimmune encephalomyelitis induced through injection of recombinant myelin oligodendrocyte glycoprotein (rMOG) when they were previously immunized intraperitoneally with rMOG adsorbed to aluminium hydroxide. This protection was associated with a decreased IFN-, production by rMOG-specific cells, but not a decreased proliferative response. Protection was long lasting, indicating that MOG-alum vaccination might be developed as a prophylactic therapy in multiple sclerosis. [source] PRECLINICAL STUDY: Long-term haloperidol treatment (but not risperidone) enhances addiction-related behaviors in mice: role of dopamine D2 receptorsADDICTION BIOLOGY, Issue 3 2009Rita C. Carvalho ABSTRACT The high prevalence of psychostimulant abuse observed in schizophrenic patients may be related to the development of mesolimbic dopaminergic supersensitivity (MDS) or nigrostriatal dopaminergic supersensitivity (NDS) in response to the chronic blockade of dopamine receptors produced by typical neuroleptic treatment. We compared the effects of withdrawal from long-term administration of the typical neuroleptic haloperidol (Hal) and/or the atypical agent risperidone (Ris) on MDS and NDS, behaviorally evaluated by amphetamine-induced locomotor stimulation (AILS) and apomorphine-induced stereotypy (AIS) in mice, respectively. We further evaluated the duration of MDS and investigated the specific role of dopamine D2 receptors in this phenomenon by administering the D2 agonist quinpirole (Quin) to mice withdrawn from long-term treatment with these neuroleptics. Withdrawal (48 hours) from long-term (20 days) Hal (0.5 mg/kg i.p.) (but not 0.5 mg/kg Ris i.p.) treatment potentiated both AILS and AIS. Ris co-administration abolished the potentiation of AILS and AIS observed in Hal-withdrawn mice. Ten days after withdrawal from long-term treatment with Hal (but not with Ris or Ris + Hal), a potentiation in AILS was still observed. Only Hal-withdrawn mice presented an attenuation of locomotor inhibition produced by Quin. Our data suggest that the atypical neuroleptic Ris has a pharmacological property that counteracts the compensatory MDS and NDS developed in response to the chronic blockade of dopamine receptors imposed by Ris itself or by typical neuroleptics such as Hal. They also indicate that MDS may be long lasting and suggest that an upregulation of dopamine D2 receptors in response to long-term treatment with the typical neuroleptic is involved in this phenomenon. [source] Colours and Metallic Sheen in Beetle Shells , A Biomimetic Search for Material Structuring Principles Causing Light Interference,ADVANCED ENGINEERING MATERIALS, Issue 4 2008T. Lenau Abstract Visual aesthetic has always played a vital role for the success of many products. This includes colours and glossiness and metal appearance which is often achieved using surface coatings. Present coating techniques do, however, have limitations. It is difficult to reach very bright and brilliant colours, colours tend to fade over time and many of the materials and coating technologies pollute and have other environmental problems. Beetles in nature have many of the desired properties: They have appealing brilliant colours and some even with metallic appearance. It is noticeable that the colours are long lasting as some of the beetles we have studied at the zoological museum are more than 200 years old and have colours and brightness as if they were still alive. Furthermore, the beetles in nature are part of sustainable ecosystems, which means that they are made from renewable materials that are broken down and recycled when the beetle dies. Beetles also possess another and very attractive property: Their metallic look originates from structures in organic materials which is both electrically and thermal insulating. The industrial perspective is to be able to manufacture products with attractive metallic surfaces that do not feel so cold to touch as their metallic counterparts and that do not represent an electrical shock hazard. [source] ,The everlasting trial of strength and patience': transitions in home care nursing as narrated by patients and family membersJOURNAL OF CLINICAL NURSING, Issue 6 2001Dip NEd, Eva Efraimsson MSc ,,The aim of this study was to describe and interpret patients' and their family members' lived experiences of caring at home. Twelve tape-recorded narratives, with seven patients and five family members, were interpreted in accordance with a phenomenological,hermeneutic method inspired by Ricoeur. ,,The findings revealed life situations where natural caring was changed into patient,care-giver relations and the home became a public room. The patients had to deal with decreased abilities and the family members with adjusting to caring needs. ,,The changes in the life situations were interpreted as long lasting and trying transitions. ,,Implications for nursing and further research are proposed. [source] Effects of the PAF receptor antagonist UK74505 on local and remote reperfusion injuries following ischaemia of the superior mesenteric artery in the ratBRITISH JOURNAL OF PHARMACOLOGY, Issue 8 2000D G Souza The effects of the long lasting and potent PAF receptor antagonist UK74505 were assessed on the local and remote injuries following ischaemia and reperfusion (I/R) of the superior mesenteric artery (SMA) in rats. In a severe model of ischaemia (120 min) and reperfusion (120) injury, in addition to the local and remote increases in vascular permeability and neutrophil accumulation, there was significant tissue haemorrhage, blood neutropenia, systemic hypotension and elevated local and systemic TNF-, levels. Post-ischaemic treatment with the selectin blocker fucoidin (10 mg kg,1) prevented neutrophil accumulation in tissue and, in consequence, all the local and systemic injuries following severe I/R. Treatment with an optimal dose of UK74505 (1 mg kg,1) also reversed local and remote neutrophil accumulation, increases in vascular permeability and intestinal haemorrhage. UK74505 partially inhibited blood neutropenia and reperfusion-induced hypotension. Interestingly, both fucoidin and UK74505 prevented the local, but not systemic, increases of TNF-, levels following severe I/R injury, demonstrating an important role of migrating cells for the local production of TNF-,. However, the results do not support a role for PAF as an intermediate molecule in the production of systemic TNF-,. The beneficial effects of UK74505 and other PAF receptor antagonists in models of I/R injury in animals and the safety of UK74505 use in man warrant further investigations of the use of this drug as preventive measure for I/R injury in humans. British Journal of Pharmacology (2000) 131, 1800,1808; doi:10.1038/sj.bjp.0703756 [source] Fatty acid composition abnormalities in atopic disease: evidence explored and role in the disease process examinedCLINICAL & EXPERIMENTAL ALLERGY, Issue 9 2008A. Sala-Vila Summary There is a hypothesis causally linking excess intake of n-6 polyunsaturated fatty acids (PUFAs) to atopic disease. Under most dietary conditions, the main precursor of eicosanoids is the n-6 PUFA arachidonic acid (AA). AA-derived eicosanoids play many roles in sensitization to allergens and in allergic inflammation. Long chain n-3 PUFAs inhibit AA incorporation into cell membranes and inhibit AA metabolism to eicosanoids. It is hypothesized that atopy is associated with a higher n-6 PUFA status and with a low n-3 PUFA status. However, measurements of fatty acid composition do not provide a clear picture that such fatty acid abnormalities exist in atopy with no really clear pattern of altered status of a particular fatty acid or a particular fatty acid family. There are few reports of elevated linoleic acid in atopy. Some studies report lower amounts of the n-6 PUFAs, including AA, and of long chain n-3 PUFAs in atopy, although observations on this are not consistent. Taken together these data clearly do not support the hypothesis that atopy is somehow associated with a high exposure to, and status of, n-6 PUFAs. Intervention studies with n-3 PUFAs in pregnant women, infants and children suggest some clinical benefits, although how long lasting these are remains to be determined. The observation that there may be low AA status in atopy suggests that fish oil intervention, which targets AA status and metabolism, may not be ideal and that a combination of fish oil with some longer chain n-6 PUFAs may be more efficacious. [source] | ||||||||||