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It could be postulated that women with IH have a primary increase in cutaneous 5 -RA activity. Jenkins and Ash 90 ; reported that in two of three women with "idiopathic hirsutism" the production of DHT from T by minces of suprapubic skin was 50 100% above the upper normal limit. Unfortunately, while these subjects with IH had normal androgen levels, no mention was made of their ovulatory function. Serafini and Lobo 91 ; studied 10 women with IH defined by the presence of hirsutism, normal androgen levels, and regular menstrual cycles ; and reported that these patients had higher levels of 5 -RA activity measured biochemically in genital skin, compared with controls. Although circulating androgens are known to increase peripheral 5 -RA activity 51, 92 ; , the circulating androgen levels were normal in the IH women studied. Hence, the investigators tentatively concluded that in the patients studied increased skin 5 -RA activity could be a primary pathophysiological event 91 ; . It possible that increased skin 5 -RA may not be a factor unique to IH and may simply reflect the development of hirsutism. For example, in the studies by Jenkins and Ash 90 ; and Serafini and Lobo 91 ; , a similar increase in skin 5 -RA activity was observed among patients with PCOS. It was proposed that, in contrast to patients with IH, the increase in peripheral 5 -RA activity in women with PCOS occurs secondarily to their higher androgen levels 91 ; . In fact, these investigators reported other data that suggest that peripheral events play a role in the development of hirsutism, even among patients with PCOS 93 ; . Hence, it is possible that the increased peripheral 5 -RA activity observed in IH simply reflects the development of hirsutism, regardless of cause. Overall, from the available data it is not possible to conclusively establish that increased 5 -RA activity plays a primary role in the development of IH. Likewise, it is still unclear which of the 5 -RA isoenzymes, if any, is predominant in the development of IH. Using molecular analysis of isoenzyme-specific mRNAs, the concentrations of the type 1 5 -RA isoenzyme in sebaceous glands was higher in patients with acne 94, 95 ; , with no significant differences in the concentration of the type 2 isoenzyme. Consistent with this finding, the use of finasteride a type 2 5 -RA inhibitor, see below ; had no effect on sebum production in men being treated for prostate hyperplasia 96 ; . Nonetheless, in contrast to acne, it is likely that the type 2 isoenzyme plays a significant role in hirsutism since finasteride is at least partially effective in its treatment 97, 98 ; . Further studies using well defined patients are required to establish the precise role of each of these isoenzymes in the development of hirsutism, and specifically IH.

Fig. 3. Schematic representation of the molecular determinants of TRAIL Apo2L-induced apoptosis of colorectal cancers. Engagement of death receptors with TRAIL Apo2L cross-activates caspase-8 and triggers caspase-8-mediated proteolytic activation of caspase-3 and BID. Our studies indicate that TRAIL Apo2Linduced apoptosis of colorectal cancer cells requires BAX for tBID-mediated release of cytochrome c and mitochondrial activation of caspase-9. Activation of NF- B by genetic aberrations such as mutations of ras or overexpression of EGFR ; may protect colorectal cancers from TRAIL Apo2L by inducing expression of survival genes that inhibit caspase-8 FLIP ; or sequester tBID Bcl-xL ; . Conversely, TRAIL Apo2L-induced death of colorectal cancers may be augmented by agents that reduce Bcl-xL expression via inhibition of NF- B peptidomimetic compounds that disrupt the IKK complex or sulindac sulfide.

4th Pan Commonwealth Veterinary Conference, 4th - 8th November 2007. Barbados, West Indies The visit was packed with wonderful learning opportunities and surpassed my expectations in all respects. The biggest challenge faced would be to try to put some of the material to use in my country. This would be an on-going and very gradual process largely due to client education and economics. Words would not fully express my appreciation to the many people who made my stay comfortable and who freely gave of their knowledge and expertise. Dr. Ross Ainslie and his wife Isabel generously provided accommodations. Mr. Peter Ainslie graciously provided explanations for questions posed on practice management, clinic organization and protocols and also transported me to and from the clinics on most days. Dr. Kelly Mc Innis made arrangements for visits to other clinics and organizations very promptly and efficiently. The level of professionalism and efficiency displayed by the organizing committee was nothing short of exemplary. All the committee members were welcoming and gracious individuals. Special thanks to Dr. Bert Stevenson S. M. Bandiera, A. Mirfazaelian and J. Sebelova. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada. The cytochrome P4502C CYP2C ; subfamily, which is active in the biotransformation of many clinically important drugs, is composed of at least four members, CYP2C8, CY2C9, CYP2C18 and CY2C19 in humans. In order to explore the relationship between hepatic CYP2C19 expression and age and sex of human subjects, we measured S ; -mephenytoin 4-hydroxylase activity and CYP19 protein expression in liver microsome samples from 40 individuals 20 male, 19 female, 1 unknown, aged 2-71 yr. ; . Hepatic CYP2C8 and CYP2C9 protein levels were also measured and compared with CYP2C19 expression. CYP2C19 protein content, determined by immunoblot analysis, and S ; -mephenytoin 4-hydroxylase activity, measured using an HPLC assay, were well correlated in all samples r 0.70, p 0.05 ; , despite large inter-individual differences. The mean S ; -mephenytoin 4hydroxylase activity was significantly greater in female than male subjects 25 6 versus 7 2 pmole min mg protein, p 0.05 ; . Likewise, hepatic CYP2C19 protein levels were greater in samples from women 3.6 0.9 pmole mg protein ; than men 1.5 0.4 pmole mg protein ; . In contrast, there was no sex difference in hepatic CYP2C8 or CYP2C9 protein levels. There was no significant correlation between S ; -mephenytoin 4- hydroxylase activity or CYP2C19 protein expression with age. Similarly, there was no significant correlation between age and CYP2C8, CYP2C9 or total CYP2C content. In summary, the results suggest that CYP2C19 expression is greater in women than men although analysis of a larger number of samples is needed before this sex difference can be verified.

Was evident in both the MTT proliferation assay, as well as in the apoptotic assays. The difference between both the antiproliferative and apoptotic effects of celecoxib versus rofecoxib is particularly noteworthy, because these drugs have quite similar potency for inhibition of the COX-2 enzyme and very similar clinical efficacy in inflammatory indications. Antiproliferative and antitumor activity of COX-inhibitory compounds have been reported previously in COX-2-negative epithelial cell lines and tumor xenografts. Recently, Williams et al. 14 ; demonstrated very similar growth inhibition curves for celecoxib in Cox-2 ; , ; , and ; mouse embryo fibroblasts. Thus, COX-2independent effects of celecoxib also were observed in nontransformed, but highly proliferative, cells of identical genetic background. Very little, however, was known about the effect of these agents on hematological cancers. The precise cellular target s ; of these COXindependent effects have not been elucidated, but potential candidates have been identified. One such candidate, the 15-lipoxygenase-1 enzyme, was shown to be up-regulated by the COX-2 inhibitor, NS-398, as well as sulindac sulfone, which is devoid of COX-inhibitory activity 20 ; . 15-lipoxygenase-1 catalyzes the production of the eicosanoid mediator, 13-S-HODE, which has both growth-inhibitory and proapoptotic effects. Sulindac sulfone and other growth inhibitory compounds have been shown to inhibit other cellular targets with potential roles in tumor cell growth, phosphodiesterases-2 and -5 21 ; . Another class of potential targets for mediation of the antiproliferative effects of NSAID-like drugs are the PPARs and ; . NSAIDs have been shown to bind to both PPARs and and mediate the prototypical biological effect of induction of differentiation in normal adipocytes 22 ; . PPAR activation has been shown to result in differentiation and growth inhibition in liposarcoma, and, in one study, the antidiabetic drug and PPAR agonist, troglitazone, was shown to have clinical antitumor effects in liposarcoma 23 ; . Preclinical anticancer effects of PPAR agonists have also been observed in breast and colon cancer models 24, 25 ; . NSAIDs have also been shown to bind PPAR , a transcription factor that has been well characterized in colon carcinoma. It is up-regulated by the -catenin signaling pathway, and its overexpression suppresses the apoptotic effect of sulindac in colon carcinoma cell lines. As opposed to the activating effects of NSAIDs on PPARs and , these drugs bind to and inhibit the function of.

PHYSICIAN DISCUSSION OF ADVANCE DIRECTIVES IN AN ETHNICALLY AND LINGUISTICALLY DIVERSE HOSPITALIZED POPULATION. S. Kulkarni1; L.S. Karliner1; A.D. Auerbach1; E.J. Perez-Stable1. 1University of California, San Francisco, San Francisco, CA. Tracking ID # 173737 ; BACKGROUND: Despite a JCAHO mandate that hospitals offer all patients the opportunity to indicate advance directives, it is unknown how often physicians actually discuss advance directives with their hospitalized patients. We set out to investigate patient report of advance directive discussion in a multi-ethnic, multilingual safety net hospitalized population. METHODS: This is a cross-sectional communication study of hospitalized patients on a general medical-surgical ward in an urban county hospital recruited between January and August of 2005. Participants were interviewed by a bilingual research assistant in Spanish or English according to patient preference. We asked patients at a baseline inpatient interview, and again at a two-week post-discharge interview, whether hospital physicians had discussed 1 ; what type of treatment they would want if they could not make decisions for themselves, and 2 ; whether they would want CPR if needed. We categorized patients as having discussed advanced directives if the reply was yes to either question at either time-point. Spanishspeaking patients were asked about language interpretation for the discussion. We examined the association of the following patient factors with advance directive discussion: age, gender, self-reported ethnicity, education, co-morbidity self-report scale ; , principal diagnosis chart review ; , and English proficiency. Patients were categorized as having limited English proficiency LEP ; if they answered the question BHow well do you speak English? either with Bnot at all or Bnot well , or if they answered Fwell , but stated a preference to receive their medical care in Spanish. RESULTS: Of the 150 participants, 92 62% ; were LEP. Mean age was 39 years T14, range 1882 ; , 89 60% ; were women, 113 76% ; Latino, 29 19% ; African American, 4 3% ; Caucasian, and 3 2% ; Asian. Only 71 47% ; patients reported physician discussion of advance directives during their hospitalization. There was no association of gender, education, ethnicity or English proficiency with advance directive discussion. There was no difference in discussion of advance directives for patients 50 years old age compared to younger patients 51% vs. 46%; p 0.6 ; , and for those with more co-morbidities. There was a suggested trend toward more discussion among patients with principal diagnoses associated with surgery trauma, orthopedic, vascular and neurosurgical ; as compared to those associated with medical admission 54% vs. 44%; p 0.3 ; . Among LEP patients who reported advance directive discussion, only half had an interpreter present during the conversation; the majority of interpreters 55% ; were family members or noninterpreter hospital staff. CONCLUSIONS: Fewer than half of the patients in our study reported having discussed advance directives with their physicians during their hospitalization. This was true, regardless of age, ethnicity, primary language, or education. Our data suggests that surgeons may be more likely to have these discussions than internists; future research should investigate this finding further.

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