Why are collagenoses dangerous for pregnancy?

It is well known that certain autoimmune disorders are associated with pregnancy loss. Increased perinatal and maternal mortality as well as increased incidence of disease deterioration during pregnancy are correlated to preconceptual disease regulation, incidence of super-imposed gestosis and renal failure and, recently, with some sorts of antiphospholipid antibodies. Indeed, investigators have attempted to establish an association between recurrent pregnancy loss and the presence of specific antibodies, irrespective of the presence of other clinical signs or complications of collagenosis. The most serious appears to be the presence of anticardiolipin antibodies and lupus anticoagulant while the significance of other autoantibodies that can be found appears to be much less defined. In the present paper pregnancy complicated by various collagenoses and therapeutic modalities are discussed.     

The CRF(1) receptor antagonist DMP696 produces anxiolytic effects and inhibits the stress-induced hypothalamic-pituitary-adrenal axis activation without sedation or ataxia in rats

Abstract Rationale. CRF₁ antagonists may be effective in the treatment of anxiety disorders while having fewer side effects compared with classical benzodiazepines. Objectives. The effects of a small molecule selective CRF₁ antagonist DMP696 on anxiety-like behaviors and stress-induced increases in corticosterone in rats exposed to a novel environment and on locomotor activity and motor coordination were determined in rats. These effects of DMP696 were compared with those produced by the classical benzodiazepine chlordiazepoxide (CDP). Methods. DMP696 or CDP were administered PO, 60 minutes before behavioral testing in rats. Their effects on latency to exit a dark chamber and stress-induced increase in corticosterone in the Defensive Withdrawal test (an animal model of anxiety), locomotor activity, and rotorod performance (measure of ataxia) were determined. Results. DMP696 significantly reduced exit latency and reversed the stress-induced increase in corticosterone in the Defensive Withdrawal test at doses of 3.0–10 mg/kg and higher. In contrast, CDP significantly decreased exit latency at 10 and 30 mg/kg, but not at 100 mg/kg, due to concurrent non-specific side effects. Unlike DMP696, CDP had no effect on the stress-induced increase in corticosterone at lower doses, but resulted in a significant increase at higher doses. DMP696 did not reduce locomotor activity or impair motor coordination at doses up to 30-fold higher than doses effective in the Defensive Withdrawal model. In contrast, CDP produced significant sedation and ataxia at the same doses that were effective in reducing exit latency. Conclusions. These data suggest that the CRF₁ antagonist DMP696 might retain the therapeutic benefits of classical benzodiazepines but have fewer motoric side effects. Electronic Publication     

Hedgehog signaling pathway and vitamin D receptor gene variants as potential risk factors in odontogenic cystic lesions

Clinical Oral Investigations - Genetic variants in the hedgehog signaling pathway and VDR gene are involved in inflammatory responses and neoplastic transformation. Current study investigated...     

Evaluation of radioprotective effects of propolis and its flavonoid constituents: in vitro study on human white blood cells

This in vitro study aimed to evaluate the possible radioprotective effects of the natural substances WSDP, caffeic acid, chrysin and naringin on γ‐irradiated human white blood cells. The effectiveness of tested compounds was evaluated using the alkaline comet assay, the analysis of structural chromosome aberration and the cytokinesis‐block micronucleus assay. The results obtained by the alkaline comet study indicate favourable toxicity profiles of propolis and its polyphenolic components, and confirmed the radioprotective abilities comparable to the chemical radioprotector AET. WSDP and its polyphenolic components were able to reduce the number of necrotic cells. None of tested compounds induced significant genotoxicity, but all of them offered a quite measurable protection against DNA damage. WSDP was found to be the most effective in diminishing the levels of primary and more complex cytogenetic DNA damage in white blood cells. Considering its complex composition, to undoubtedly explain the underlying mechanisms of cyto/radioprotective effects, further studies are needed. Copyright © 2009 John Wiley & Sons, Ltd.     

Harmonic scalpel in transanal microsurgery

BACKGROUND/AIMS: Retrospective clinical study of patients with rectal tumors treated by transanal endoscopic microsurgery (TEM) using Ultracision. METHODS: From 1997-2006 54 patients were treated by excision of the rectal tumors situated in the middle and distal portion, using the harmonic scalpel. We treated 25 male (range 40-76 years) and 29 female (range 46-80 years) patients. Tumors were benign or well or moderately differentiated carcinomas in stage T1N0M0 or T2N0M0. Excision was done by Ultracision (UltraCision, Ethicon Endo-Surgery) to all patients. Preoperative examinations were: colonoscopy, biopsy, tumor markers, CT, transanal ultrasound, pelvic NMR, gynecological exam in females. The tumors were excised by harmonic scalpel after submucosal infiltration of adrenalin (1: 200 000) and 2% lidocaine. RESULTS: There was no morbidity or mortality in this group of patients. Histopathology was: Adenoma tubovillosum in alteratio maligna 20, adenocarcinoma (T1N0M0) 6, (T2N0M0) 8, adenocarcinoma with lymphatic vessels and perineural spaces invasion 1, adenoma villosum 12 and adenoma tubulare 7. After surgical treatment 8 patients underwent adjuvant radiotherapy. There was no local recurrence during this period. CONCLUSIONS: TEM is a method of choice in the treatment of rectal benign tumors and malignant tumors in stage T1N0M0, grade 1 and 2. Harmonic scalpel provides a safer, easier, and more precise surgical section through clean, bloodless and better visualized operative field.     

Interconversion between two unrelated protein folds in the lymphotactin native state

Proteins often have multiple functional states, which might not always be accommodated by a single fold. Lymphotactin (Ltn) adopts two distinct structures in equilibrium, one corresponding to the canonical chemokine fold consisting of a monomeric three-stranded beta-sheet and carboxyl-terminal helix. The second Ltn structure solved by NMR reveals a dimeric all-beta-sheet arrangement with no similarity to other known proteins. In physiological solution conditions, both structures are significantly populated and interconvert rapidly. Interconversion replaces long-range interactions that stabilize the chemokine fold with an entirely new set of tertiary and quaternary contacts. The chemokine-like Ltn conformation is a functional XCR1 agonist, but fails to bind heparin. In contrast, the alternative structure binds glycosaminoglycans with high affinity but fails to activate XCR1. Because each structural species displays only one of the two functional properties essential for activity in vivo, the conformational equilibrium is likely to be essential for the biological activity of lymphotactin. These results demonstrate that the functional repertoire and regulation of a single naturally occurring amino acid sequence can be expanded by access to a set of highly dissimilar native-state structures.