Low-dose radiotherapy (LD-RT) and the modulation of iNOS expression in adjuvant-induced arthritis in rats

PURPOSE: Low-dose radiotherapy (LD-RT) of arthritic joints applied during the peak of the acute inflammatory response improves the clinical and histomorphological development of adjuvant arthritis. The study was undertaken to investigate the cellular composition of the inflammatory infiltrate and the expression of the pro-inflammatory and anti-inflammatory enzymes, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX-2) and haem-oxygenase 1 (HO-1), in response to LD-RT. MATERIALS AND METHODS: Adjuvant arthritis in female Lewis rats was induced by intradermal injection of heat-inactivated mycobacterium tuberculosis on day 0. Both arthritic hind paws were sham irradiated (group 1) or X-irradiated with either 5 x 1.0 Gy (group 2) or 5 x 0.5 Gy (group 3) from days 15 to 19 after induction (15 animals/group). On days 21 (n=12 joints/group) and 30 (n=18 joints/group), cryostat sections were analysed histologically and immunohistologically after specific staining for macrophages, iNOS, COX-2 and HO-1. RESULTS: A total of 5 x 1.0 Gy or 5 x 0.5 Gy led to a significant reduction of clinical symptoms from days 21 to 29, and a highly significant reduction of cartilage and bone destruction on day 30. Macrophage-positive areas could be detected continuously throughout the periarticular infiltrate, and were slightly reduced after LD-RT on days 21 and 30. This reduction was more pronounced after 5 x 1.0 Gy. Following LD-RT, the iNOS score was reduced by about 45-50% on days 21 (p<0.05) and 30 (p<0.001). In contrast, the HO-1 score was increased by about 50% on days 21 (p=0.08) and 30 (p=0.03). CONCLUSIONS: The clinically and histologically observed prevention of the progression of adjuvant arthritis after LD-RT given during the peak of the acute inflammatory response and the reduction of cartilage and bone destruction in the chronic phase appears to be related to the modulation of iNOS activity by low X-ray doses.     

Diterpenoids from Tetraclinis articulata that inhibit various human leukocyte functions

Ten new compounds, eight of them pimarane derivatives (1-8), together with a menthane dimer (9) and a totarane diterpenoid (10), were isolated from the leaves and wood of Tetraclinis articulata. The structures of 1-10 were established by using spectroscopic techniques, including 2D NMR spectra. Pimaranes 1-5 were found to possess an unusual cis interannular union of the B and C rings, which, from a biogenetic perspective, could be derived from the hydration of a carbocation at C-8. Compounds 4-6 and a mixture of 7 and 11 modulated different human leukocyte functions at a concentration of 10 microM, mainly the degranulation process measured as myeloperoxidase release and, to a lesser extent, the superoxide production measured by chemiluminescence.     

Health-related needs of the displaced population due to armed conflict in Bogotá

BACKGROUND: The displacement of populations as the result of an armed conflict generally entails a worsening of the living and health conditions of those undergoing such a displacement. This paper is aimed at analyzing the health-related needs perceived by men and women displaced by the armed conflict and their main strategies to address those needs. METHODS: A qualitative study was carried out by means of semi-structured individual interviews to 31 displaced men and women in the transition stage. A narrative analysis of the contents was conducted, segmenting the information by age and sex. The area under study was made up of five localities in the city of Bogotá. RESULTS: The negative effects on their mental health and psychosocial stability, access to food and, to a lesser degree, gastrointestinal and respiratory disorders, are the main health problems reported by both groups of informants. The difficulty of accessing health care services comes up as an added problem. The precarious economic situation underlies the health care-related needs and problems. To solve their health problems, in addition to the health care services, they employ other strategies within their reach. Expressed needs are coherent with the problems perceived. Some differences between women and men and age groups were observed concerning the definition of the problems and employed strategies. CONCLUSION: In the health field, actions are required in order to improve their access to services in addition to specific strategies for the psychosocial rehabilitation of the displaced population which take into account the differences existing within this group.     

Enhanced anti-inflammatory potency of a nitric oxide-releasing prednisolone derivative in the rat

1. Derivatization of nonsteroidal anti-inflammatory drugs, such that they release nitric oxide (NO) in small amounts, has been shown to significantly increase their anti-inflammatory activity and analgesic potency. In this study, we compared the anti-inflammatory potency of prednisolone to a nitric oxide-releasing derivative of prednisolone (NCX-1015). 2. Carrageenan-induced inflammation of an airpouch in the rat was used. The rats were pretreated with equimolar doses of prednisolone or NCX-1015 and the effects on leukocyte infiltration into the airpouch and exudates levels of prostaglandin E(2) (PGE(2)), leukotriene B(4) (LTB(4)) and nitrite (as an index of NO production) were measured 6 h later. 3. Injection of carrageenan into the airpouch resulted in a progressive increase in leukocyte infiltration, and accumulation of PGE(2), LTB(4) and nitrite. Carrageenan also induced elevated expression of cyclooxygenase-1 and -2, inducible nitric oxide synthase and 5-lipoxygenase in the inflammatory exudate. 4. Prednisolone dose dependently reduced the numbers of leukocytes within the airpouch exudates, as well as reducing PGE(2), LTB(4) and nitrite levels. NCX-1015 also reduced leukocyte numbers and inflammatory mediator levels. However, the doses of NCX-1015 required to produce a maximal reduction of each of these parameters was one-third to one-tenth the dose of prednisolone that produced a comparable effect. 5. The reduction of PGE(2) and NO production was likely to be at least in part due to reduced expression of the key enzymes responsible for their synthesis (cyclooxygenase-2, inducible NO synthase), with NCX-1015 producing greater suppression than prednisolone at an equimolar dose. 6. Coadministration of prednisolone with a nitric oxide donor (DETA-NONOate) resulted in a greater reduction of leukocyte infiltration and inflammatory mediator production than was observed with either drug alone. 7. These results support the notion that delivery of NO to a site of inflammation can markedly enhance the anti-inflammatory activity of a glucocorticoid.     

Sulfated polysaccharides of brown seaweed Cystoseira canariensis bind to serum myostatin protein

Natural sulfated polysaccharides (SPs) derived from brown seaweed comprise a complex group of macromolecules with a wide range of important physiological properties. SPs have been shown to bind and directly regulate the bioactivity of growth factors and cytokines such as basic fibroblast growth factor, interferon, various enzymes and transforming growth factor. Myostatin is a member of the transforming growth factor-beta (TGF-beta) family that acts as a negative regulator of skeletal muscle mass. In this work we demonstrated that SPs isolated from the brown seaweed Cystoseira canariensis bind to the myostatin protein in serum.     

Structural characterization of two CD1A allelic variants

CD1 molecules are specialized in presenting lipidic antigens to T lymphocytes. They are structurally and evolutionary related to MHC molecules and show very limited polymorphism. We have previously described and partially characterized a new human CD1A allele differing from the wild type CD1A by a substitution of Cysteine by Tryptophan at position 52 in the alpha1 domain of the CD1A molecule. The frequency of this allele varies from 10% in individuals of Caucasian origin to 56% in Chinese people. The aim of the present work was to structurally characterize this CD1A allele. To do this we have cloned and sequenced the full-length cDNA encoding the new CD1A allele. The cDNA sequence of this allele encodes a protein differing the wild type in two amino acids at positions 14 (Threonine versus Isoleucine) and 52 (Cysteine versus Tryptophan). The cDNAs encoding both wild type and mutant CD1A were cloned in the expression vector pSRalphaNeo and transfected into C1R and L721.221 cells. Cell surface expression of the protein products in transfected cell lines were analyzed by flow cytometry and immunoprecipitation using CD1a-specific monoclonal antibodies. Our results indicate that both allelic products are efficiently expressed on the cell surface.     

Abdomen release in prone position does not improve oxygenation in an experimental model of acute lung injury

OBJECTIVE: To analyze the effect of abdomen release in the prone position on oxygenation in an experimental model of acute lung injury. DESIGN: Experimental randomized controlled study. SETTING: Experimental laboratory of a tertiary university hospital. PARTICIPANTS: Mixed-breed adolescent pigs weighing between 25-31 kg. INTERVENTIONS: Thirty minutes after pulmonary edema was produced with oleic acid, the animals were turned prone and randomized into two groups: group I or control (n = 9), lying directly on the operating table; and group II (n = 11) with abdomen release, with positioning rolls under the upper part of the chest wall and the pelvis to allow free movement of the abdomen. MEASUREMENTS AND RESULTS: The gas exchange, respiratory mechanics, hemodynamics, intra-abdominal pressure (IAP) and the extravascular lung water (EVLW), determined by double indicator dilution method (DI), were recorded at baseline (time 0) and at 30, 60, 90, 120 and 150 min. The PaO2/FIO2 increased in both groups at 30 min after the pigs were placed in the prone position (time 60) and then decreased progressively until the end of the experimental period, with no statistical differences between the groups at any time (73.1 +/- 14.5 vs 79.5 +/- 14.9 at 150 min). Abdomen release was not associated with changes in the respiratory mechanics, EVLW or intra-abdominal pressure. CONCLUSIONS: Abdomen release in prone position does not improve oxygenation in an experimental model of acute lung injury.