Anti-inflammatory glucocorticoids inhibit prostaglandin (PG) biosynthesis by preventing arachidonic acid release from phospholipids rather than inhibiting the cyclooxygenase. As in other cells, this steroid action depends on receptor occupation and de novo protein/RNA biosynthesis. We have previously shown in guinea pig perfused lungs and rat peritoneal leukocytes that the effect of steroids in PG generation is mediated by an uncharacterized 'second messenger'. Now, we report that this factor (which we have named 'macrocortin') is an intracellular polypeptide whose release and synthesis are stimulated by steroids. Macrocortin derived from rat peritoneal leukocytes is very similar to that released from guinea pig lungs.
Neutrophils are the most abundant white blood cells and are the first recruited to inflammatory sites. Neutrophils are an important component of the tumor stroma and can exert both anti-tumoral and pro-tumoral activities, depending on their maturation and activation state. In human gliomas, the number of circulating and infiltrating neutrophils correlates with the severity of the disease, indicating a prognostic and possible pro-tumoral role for these leukocytes. In glioma preclinical models, neutrophils promote tumor growth and orchestrate the resistance to anti-angiogenic therapies. Nevertheless, recent data indicate that neutrophils can be activated to directly kill tumor cells or to orchestrate the anti-tumoral response. Here, we review current knowledge about the role of neutrophils in glioma and their possible involvement in new strategies to improve current cancer therapies.
It has been suggested that first polar body (PBI) morphology reflects oocyte competence. Oocytes with an intact normal-sized PBI have been described as generating better day 2 embryos, higher blastocyst yield, and increased pregnancy and implantation rates. In other studies, PBI morphology was found to be unrelated to fertilization rate, embryo quality, and blastocyst formation. In a prospective analysis, the predictive value of the PBI was investigated by comparing the development of oocytes retrieved from intracytoplasmic sperm injection patients and displaying different PBI morphology, classified according to the following characteristics: normal size and smooth surface (I), fragmented (II), rough surface (III), or large size (IV). Fertilization rates were 59, 57, 64 and 60% respectively. No significant differences were found between the various groups. The proportions of high quality (grade A) day 2 embryos were also comparable among groups I-III (14, 12 and 17% respectively), while the low number of grade A embryos in group IV (two embryos) did not allow comparison with the other classes. These data do not suggest that PBI selection can contribute to identification of embryos with high developmental ability. In order to establish alternative criteria for oocyte selection, a metaphase II (MII) spindle analysis was also conducted via Polscope. In oocytes of patients of different age, spindle retardance (which reflects the high order and density of microtubules) was compared with parameters of embryo development. In aged patients, a trend was observed between low retardance and poor embryo quality, although in general the association between retardance and oocyte developmental performance did not reach statistical significance.
A previously validated 15-item questionnaire on dogs' life quality (QoL1) and that of their owners (QoL2) was applied in a multicentre study to owners of 200 dogs with different dermatological conditions, together with a question on the owner-perceived disease severity (S). Factor analysis was applied to the whole questionnaire. The correlation of S with QoL1 and QoL2 scores was evaluated using Spearman's rank correlation tests. Owner sex, age, educational level and willingness to pay for a potential definitive cure of the disease were recorded, and compared with quality of life (QoL) scores. In 23 atopic dogs, CADESI-03, pruritus Visual Analogue Scale and QoL scores were obtained before and after therapy, and their correlation was evaluated with linear regression. Factor analysis revealed that three factors (S, QoL1 and QoL2) explained 75% of the variance. Owner-perceived severity correlated significantly with QoL1 and QoL2 (P = 0.002 and P = 0.015, respectively). The five diseases with the worst QoL scores were scabies, pododermatitis, complicated atopic dermatitis, pemphigus foliaceus and endocrine alopecia. Pruritic diseases did not give significantly higher QoL1 or QoL2 scores compared with nonpruritic diseases (P = 0.19, Kruskall-Wallis test). Owner sex, age or educational level did not influence QoL scores. Female sex, a younger age and a higher educational level were significantly associated with more willingness to pay. In atopic dogs, all the scores decreased after therapy, but post-treatment CADESI-03 and Visual Analogue Scale scores did not correlate with QoL1 and QoL2. Questions related to the burden of maintenance therapy showed the lowest improvements in score.
1 Dexamethasone and hydrocortisone induce the release of anti-phospholipase proteins into the peritoneal cavities of rats. 2 Adrenocorticotrophic hormone (ACTH) also releases these proteins in normal but not in adrenalectomized rats. 3 Peritoneal lavage proteins were separated by ion-exchange and size exclusion chromatography. The anti-phospholipase activity occurred in four separate fractions with the major component having an apparent mol.wt. of 40 k. 4 Column fractions containing these anti-phospholipase proteins had anti-inflammatory effects in the rat carrageenin pleurisy model whereas other fractions were inactive. 5 The proteins appear to be identical to macrocortin and lipomodulin, the 'second messengers' of glucocorticoid hormone action on the arachidonate system.
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