Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

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Scope and limitations of limb-sparing surgery in childhood sarcomas

The authors reviewed 43 children with high-grade sarcomas of bone and soft tissue who underwent surgery during the past 9 years. Twenty-six patients had osteosarcoma, 7 had Ewing sarcoma, and 10 had soft tissue sarcomas. Patients ranged in age from 4 months to 13 years. Mean follow-up period was 6 years. The feasibility of resection, results of local resection, and failure of local disease control were reviewed. Limb salvage was feasible in 81% of patients. Of the 35 patients undergoing limb salvage, margins were considered adequate in 88% and inadequate in 12%. Limb-sparing resection was not feasible in 19% of patients. Five patients (four with metastatic disease at presentation) did not undergo surgery and were given palliative care; three other patients underwent amputation. The decision of whether to proceed with limb salvage surgery must depend on the aggressiveness of the underlying tumor, its stage, the feasibility of obtaining tumor-free resection margins, and the response to neoadjuvant therapy.     

Effect of desogestrel on blood-lipid in relation to its biological activities

Desogestrel (DG), a 19-nor progestin, is widely used in replacement therapy as a contraceptive steroidal hormone. Considering the importance of its partition coefficient parameter (log P = 5.68), a significant contributor to its action mechanism, interactions of the drug with blood-lipids had been investigated using phospholipid binding, fatty acid composition and peroxidation phenomena as the parameters under investigation to explain its pharmacodynamic behavior. From the present investigation, it was observed that lipid loss after incubation of whole blood with DG (80 ng/ml, effective contraceptive concentration in blood) for varying periods of time was accompanied with significant changes in fatty acid composition, which may be ascribed to binding affinity of DG with lipid constituents in blood that may have a role in the mediation of its therapeutic effect. Lipid peroxidation induction potential of DG has been quantitatively measured in the context of its toxicity. The results reveal that DG caused significant extent of lipid peroxidation. Ascorbic acid, an antioxidant, at equivalent human dose of 250 mg could significantly reduce DG-induced lipid peroxidation.     

Amygdala priming results in conditioned place avoidance

Priming involves daily stimulation of the basolateral nucleus of the amygdala (BLA) for 5 days using a dose of the GABA(A) receptor antagonist, bicuculline methiodide (BMI), that is subthreshold to generate anxiogenic-like responses. The coordinated physiological and behavioral response of the primed rat is similar to the symptoms of human panic disorder and has been used as a model to study panic attacks. If the priming procedure is indeed similar to human panic disorder, then the context in which priming occurs should become associated with aversive conditioning and avoidance as seen in secondary agoraphobia following panic attacks in humans. Therefore, the purpose of this study was to further characterize the behavioral response of priming using the conditioned place avoidance (CPA) task that utilizes distinct tactile cues of a grid floor (Grid+) or hole floor (Grid-). Male Wistar rats (275-300 g) were implanted bilaterally with guide cannulae positioned 1 mm above the BLA. Grid+ animals were placed in the conditioning chamber containing grid floors immediately after a 6-pmol (in 250 nl) BMI injection into the BLA and on hole floors following a sham (250 nl vehicle) injection. Grid animals were placed in the chamber containing hole floors after the BMI injection and on grid floors following the sham injection. Animals were placed in the chamber for 20 min following each injection and injections were separated by 4 h. After 5 days of this treatment, the animals were primed. Two days later, during avoidance testing, each animal was placed in the chamber containing both floors for 30 min. Priming with daily 6-pmol BMI injections into the BLA results in CPA or an aversion to the floor paired with the BMI injection. These results suggest that priming may result in phobic-like responses, similar to the avoidance behavior exhibited by panic disorder patients.