Purpose: Bcl-x L overexpression is common in head and neck squamous cell carcinomas (HNSCC) and correlates with resistance to chemotherapy. Thus, a nonpeptidic, cellpermeable small molecule that mimics the BH3 domain of proapoptotic proteins may inhibit Bcl-x L function and have therapeutic potential for HNSCC by overcoming drug-resistance. (؊)-Gossypol, the levorotatory isomer of a natural product isolated from cottonseeds and roots, was recently discovered to bind to the BH3 binding groove of Bcl-x L and Bcl-2.Experimental Design: We investigated the in vitro effects of (؊)-gossypol on HNSCC cell lines as well as on fibroblast and keratinocyte cultures by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell survival assays and assessed the results with respect to Bcl-2 family protein expression.Results: We observed dose-dependent growth inhibition of 10 HNSCC cell lines at biologically achievable doses (2.5-10 mol/L). (؊)-Gossypol doses required to inhibit the growth of human fibroblast cell lines by 50% were 2-to 10-fold higher than for HNSCC cell lines. To inhibit human oral keratinocyte growth by 50%, (؊)-gossypol concentrations were 2-to 3-fold higher than for HNSCC cell lines.Conclusions: There is a direct correlation between Bclx L -to-Bcl-x S ratios and sensitivity to (؊)-gossypol. This agent induced apoptosis in a much higher proportion of cells with wild-type p53. Importantly, cell lines resistant to cisplatin were very sensitive to (؊)-gossypol. These results demonstrate that (؊)-gossypol has potent antitumor activity in HNSCC in vitro. This agent may be developed as a novel therapeutic agent for HNSCC, either alone or in combination with existing chemotherapeutic agents.

Our novel modifications to the island palatal flap yield a large (12-18 cm(2)) mucoperiosteal flap based on a approximately 3 cm pedicle. The Oliver pedicled palatal flap shows potential for nasal cavity and skull base reconstruction (see video, available online only).

BackgroundMigraine is a common neurovascular condition that may be linked to hyperhomocysteinemia. We have previously provided evidence that reduction of homocysteine with a vitamin supplementation can reduce the occurrence of migraine in women. The current study examined the occurrence of migraine in response to vitamin supplementation with a lower dose of folic acid.MethodsThis was a 6 month randomised, double blinded placebo controlled trial of daily vitamin supplementation containing 1 mg of folic acid, 25 mg of Vitamin B6 and Vitamin B12, on reduction of homocysteine and the occurrence of migraine in 300 female patients diagnosed with migraine with aura.ResultsVitamin supplementation with 1 mg of folic acid, did not significantly decrease homocysteine levels (P = 0.2). The treatment group did not show a significant decrease in the percentage of participants with high migraine disability, severity or frequency at the end of the 6 month intervention (P > 0.1).Conclusion1 mg of folic acid in combination with vitamin B6 and B12 is less effective in reducing migraine associated symptoms compared to the previously tested dosage of 2 mg folic acid in combination with 25 mg of vitamin B6 and 400 μg of vitamin B12.

The transposition of pedicled buccinator muscle flaps with and without mucosa into the nasal cavity could reach the anterior skull base and planum sphenoidale, if the appropriate surgical technique is used. The pedicled Facial Buccinator Flap holds significant potential as a reconstructive alternative for a variety of skull base defects, alone or in combination with existing reconstructive options. 2010.

Background: There is evidence for an adaptive role of the omega -3 fatty acid, docosahexaenoic acid (DHA) during stress. Mechanisms of action may involve regulation of stress mediators, such as the catecholamines and proinflammatory cytokines. Prevention of stress-induced aggression and hostility were demonstrated in a series of clinical trials. This study investigates whether perceived stress is ameliorated by DHA in stressed university staff.

Aberrant overexpression of antiapoptotic members of the Bcl-2 protein family, including Bcl-2 and Bcl-XL, contributes to malignant transformation and subsequent resistance to traditional chemotherapeutics. Thus, these proteins represent attractive targets for novel anticancer agents. The small molecule, gossypol, was initially investigated as a contraceptive agent, but subsequently has been shown to possess anticancer properties in vitro and in vivo. Recently gossypol has been found to bind to Bcl-XL and, with less affinity, to Bcl-2. Here we investigate the ability of the (−) enantiomer of gossypol, (−)-gossypol, to overcome the apoptosis resistance conferred by Bcl-2 or Bcl-XL overexpression in Jurkat T leukemia cells. (−)-Gossypol potently induced cell death in Jurkat cells overexpressing Bcl-2 (IC50, 18.1 ± 2.6 μmol/L) or Bcl-XL (IC50, 22.9 ± 3.7 μmol/L). Vector-transfected control cells were also potently killed by (−)-gossypol (IC50, 7.0 ± 2.7 μmol/L). By contrast, the chemotherapy drug etoposide only induced efficient killing of vector-transfected cells (IC50, 9.6 ± 2.3μmol/L). Additionally, (−)-gossypol was more efficient than etoposide at inducing caspase-3 activation and phosphatidylserine externalization in the setting of Bcl-2 or Bcl-XL overexpression. (−)-Gossypol-induced apoptosis was associated with Bak activation and release of cytochrome c from mitochondria, suggesting a mitochondrial-mediated apoptotic mechanism. Moreover, (−)-gossypol treatment of isolated mitochondria purified from Bcl-2-overexpressing cells also resulted in cytochrome c release, indicating a possible direct action on Bcl-2 present in the mitochondrial outer membrane. Taken together, these results suggest that (−)-gossypol is a potent and novel therapeutic able to overcome apoptosis resistance by specifically targeting the activity of antiapoptotic Bcl-2 family members. (−)-Gossypol may be a promising new agent to treat malignancies that are resistant to conventional therapies.

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The Sinopsys Surgical Lacrimal Stent has flow characteristics that are similar to a Pyrex Jones tube. Drainage in the nose via a CDCR procedure is similar to drainage in the ethmoid and maxillary sinuses via a CE and CM, respectively.