Anti-thyroid drugs decrease mucosal damage in a rat model of experimental colitis

Background : Methimazole, an anti-thyroid drug, was recently found to be useful in the treatment of systemic lupus erythematosus and other autoimmune diseases. Moreover, decreased thyroid hormone production is associated with a variety of immunological manifestations, such as reduced activation of CD4⁺ cells, increased CD8⁺ cell activity and reduced soluble IL-2 receptors. In the present study we examined the effects of methimazole and propylthiouracil on a rat model of experimental colitis.
Methods : Colitis was induced by intracolonic administration of 30 mg trinitrobenzene sulphonic acid (TNB). Two weeks prior to induction of colitis, rats were treated by either methimaziole (0.04%) or propylthiouracil (0.01%) in drinking water after a week of free access to water. Rats were sacrificed 48 h or 7 days after induction of colitis. The colon was isolated, rinsed with ice-cold water and weighed. Damage was assessed both macroscopically and microscopically and myeloperoxidase (MPO) activity determined.
Results : All treated rats were hypothyroid as manifested by a significant elevation of thyroid stimulating hormone (TSH), by comparison with the control groups (mean -1.82±0.40 versus 0.11±0.02 mmol/L, respectively). The inflammatory response elicited by TNB resulted in severe mucosal damage 48 h after damage induction, which persisted for 7 days. Pre-treatment with either methimazole 0.04% or propylthiouracil 0.01% significantly decreased mucosal damage macroscopically (lesion area, lesion score and segmental weight) microscopically and also significantly decreased MPO level at both time points ( P <0.01).
Conclusions : Methimazole and propylthiouracil significantly reduce mucosal damage and colonic weight in a rat model of colitis. The mode by which they do so remains to be studied.     

Physical Stability of Solid Dispersions Containing Triamterene or Temazepam in Polyethylene Glycols

The effect of storage on the physical stability of solid dispersions of triamterene or temazepam in polyethylene glycols was studied using differential scanning calorimetry (DSC), particle-size analysis and dissolution methods. The enthalpies of fusion of the carriers, without included drug and previously fused and crystallized, increased on storage. Analysis of similarly treated solid dispersions, containing either 10% temazepam or 10% triamterene, showed that each drug influenced the morphology of the polyethylene glycol (PEG). The enthalpies and melting points of the solidus components of the dispersions' carriers were initially reduced after preparation, but on storage these increased. The particle sizes of the drugs dispersed in the PEGs increased on storage. The changes in dissolution after storage of triamterene or temazepam dispersions were smaller for dispersions in PEG 1500 than for dispersions in PEGs of higher molecular weight (PEG 2000, PEG 4000 or PEG 6000) in which the reduction in dissolution was particularly marked during the first month of storage. The rank order of changes in dissolution were PEG 1500 ? PEG 2000 < PEG 4000 ～ PEG 6000.     

Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice.

The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.     

Transition theory and its relevance to patients with chronic wounds.

A wound, in the broadest sense, is a disruption of normal anatomic structure and function. Acute wounds progress through a timely and orderly sequence of repair that leads to the restoration of functional integrity. In chronic wounds, this timely and orderly sequence goes awry. As a result, people with chronic wounds often face not only physiological difficulties but emotional ones as well. The study of body image and its damage as a result of a chronic wound fits well with Selder's transition theory. This article describes interviews with seven patients with chronic wounds. The themes that emerged from those interviews were compared with Selder's theory to describe patients' experience with chronic wounds as a transition process that can be identified and better understood by healthcare providers.     

Bullous pemphigoid in association with cutaneous lesions specific to a myelodysplastic syndrome

Specific cutaneous lesions are a rare occurrence in myelodysplastic syndromes (MDS). The concurrent association of blistering skin lesions similar to those in bullous pemphigoid (BP), even though a rare event, suggests that BP may be a paraneoplastic syndrome. We report an 86-year-old man who had a refractory anaemia with excess bone marrow blasts in transformation, who developed a generalized pruritic blistering eruption. Immunohistopathological tests showed subepidermal blisters with linear deposits of IgG and C3 along the basement membrane zone of the epidermis surrounding a tumoral dermal infiltrate of CD13+ and CD15+ cells. Immunoblotting studies using epidermal extracts revealed circulating IgG antibodies against three protein bands: a 210–215 kDa band. a 180kDa band which co-migrated with the BP 180 antigen, and a 190kDa band. The tumour infiltrate may have revealed antigenic determinants which led to the onset of BP. The concept of paraneoplastic pemphigoid remains to be either confirmed or invalidated by further epidemiological studies.     

Effect of UVB 311 nm irradiation on normal human skin

Ultraviolet radiation B (UVB) on the skin induces erythema, inflammation and modifications of the immune system. These changes have been reported after excessive short-term or long-term exposure to broad spectrum UVB. In this study, we examined the effects of local repetitive UVB irradiation of 311 nm wavelength on the skin of seven young volunteers. Skin biopsies were taken before and after UVB irradiation, and we immunohistochemically analyzed the expression of CD1a and HLA-DR antigens of Langerhans cells (LC), the possible infiltration of dermis/epidermis by CD11b macrophages, the modifications or the induction of intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) involved in the binding of leukocytes to the endothelial surface and the development of perivascular infiltrates of LFA-1⁺ mononuclear cells. We also determined the expression of substance P receptors (SPR) using biotinylated substance P (SPB). Exposure of UVB 311 nm induced a drastic reduction of CD1a⁺ cells and a moderate increase of HLA-DR⁺ dendritic cells in the epidermis without infiltration by CD11b macrophages. An increase of the binding of SPB to upper layer epidermal cells was noted in five of seven biopsies. In the dermis, vessel-associated ICAM-1 expression increased and an induction of E-selectin occurred on nearly 20 to 40% of endothelial cells, but VCAM-1 expression remained undetectable. The percentage of LFA-1⁺ cells did not change significantly after irradiation. These observations may be compatible with a selective role of UVB 311 nm on the skin immune response.     

Measurement properties of quantitative urine benzoylecgonine in clinical trials research

Psychometric data are presented which examine the validity of using the concentration of benzoylecgonine in urine, a major metabolite of cocaine, as a measure of drug use, in studies of drug abuse treatments. In such research the standard biological indicator of drug use is usually a qualitative urine drug test, which merely indicates the presence or absence of a drug or its metabolite. A quantitative (i.e. continuous) outcome measure, such as the concentration of a drug or its metabolite in a biological fluid, has substantially more statistical power than a dichotomous measure and should, therefore, prove a more sensitive measure of drug use when viewed from a measurement perspective. Data from two placebo-controlled clinical trials of fluoxetine as an adjunct to treatment for cocaine abuse are analyzed to address this issue. Results indicate that urine benzoylecgonine level is closely related to self-reports of drug use and is independent of levels of anxiety, depression and hopelessness.     

Reduced alcohol use in pregnancy and changed attitudes in the population

The objectives of this study were to investigate (1) changes in consumption of alcohol among pregnant women over a period of 5 years (1984/85–1990), (2) changes of attitudes towards drinking during pregnancy in the general population over the same period of time, and (3) possible connections between (1) and (2). The investigation was designed as a cross-sectional study. Our subjects were two representative samples of pregnant women in Oslo, n = 577 and 425, and two representative samples of the Norwegian population, n = 1004 and 1204. The main outcome measures were a self-completed questionnaire for the pregnant women and a personal interview for the general population sample. There was a significant reduction (50% decrease) in alcohol consumption among the second cohort of pregnant women compared with the first. Furthermore, we found an increase during the 5-year period in the number of persons with a restrictive attitude towards alcohol use during pregnancy. There seems to be a connection between these two phenomena, but with our present state of knowledge it is hard to say anything about the causal relationship between them.     

Results of arthroscopic acromioplasty related to rotator cuff lesions

Summary Seventy-nine patients with a history of the subacromial impingement syndrome were treated by arthroscopic acromioplasty. The results were evaluated with a new scoring system designed to assess subjective symptoms before and after operation. The outcome was related to the pathological lesions of the rotator cuff seen at arthroscopy and graded by our modification of the Neer classification. The overall results were satisfactory in 67%, with men having better results than women. Those with a history of injury did better than those without, and the results in those with partial or total cuff tears were better than those with intact cuffs. Since the state of the cuff affects the result, arthroscopy should precede acromioplasty.

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Résumé Soixante dix-neuf patients, présentant depuis 3.5 ans (±1.8) un syndrome de conflit sousacromial, ont été traités par acromioplastie arthroscopique. Les résultats ont été évalués au moyen d'une nouvelle cotation, mesurant la symptomatologie subjective avant et 17 mois en moyenne après l'intervention chirurgicale. On a étudié le rapport entre ces résultats et la morphologie pathologique de la coiffe des rotateurs, constatée lors de l'arthroscopie et classée conformément à notre version modifiée, décrite précédemment, de la classification de Neer. Les résultats globaux étaient satisfaisants dans 67% des cas. Les résultats étaient nettement meilleurs chez les hommes que chez les femmes. Ils étaient significativement meilleurs chez les patients pour qui la symptomatologie était apparue après un traumatisme violent, de même lorsqu'il existait une rupture totale ou partielle de la coiffe des rotateurs. L'état de la coiffe influence les résultats de l'acromioplastie, pour pouvoir le déterminer il faut pratiquer une arthroscopie préalable.