"Window of Opportunity" in Ocular Graft-Versus-Host Disease Treatment: Results of a Longitudinal Study and Case Reports.

OBJECTIVE: To perform a longitudinal study for determining the development of ocular graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplant (HSCT) and report cases that illustrate the "window of opportunity" concept in oGVHD treatment. METHODS: Patients (n=61) were examined at prescheduled clinic visits before HSCT and three-month intervals after HSCT for 2 years. The presence or absence of oGVHD was determined using the international chronic oGVHD consensus group diagnostic criteria. Ocular surface washings (OSW) were obtained at each visit and analyzed for cytokine levels. RESULTS: In the longitudinal study, 26.2% (n=16; progressed group) developed either probable (11.5%, n=7) or definite oGVHD (14.8%, n=9). In the progressed group, clinically significant changes in signs (corneal staining and Schirmer I test) and symptoms at the post-HSCT visit as compared with the pre-HSCT visit occurred at 9 months. Significant differences in clinical signs and symptoms (whether average post-HSCT values or changes in values over pre-HSCT levels) between the progressed and nonprogressed groups occurred at a 9-month visit or later. In the progressed group, 55.6% of eyes that had negative matrix metalloproteinase 9 (MMP-9) test at pre-HSCT turned MMP-9 positive at 3 to 6 months post-HSCT. In the progressed group, interleukin 8 levels in OSW were significantly increased at 6 months post-HSCT. In the case reports, the "window of opportunity" was detected by MMP-9 turning positive, early corneal staining, interleukin 8 increase in OSW, and peripheral corneal epithelial thinning, which resolved with treatment initiation. CONCLUSIONS: A "window of opportunity" exists before patients developing symptomatic tear-deficient dry eye after HSCT for initiating treatment that may preempt oGVHD development; however, larger-scale longitudinal studies are needed for definitive recommendations.

Donor-Acceptor Stenhouse Adducts: Exploring the Effects of Ionic Character.

The effects of solution-state dielectric and intermolecular interactions on the degree of charge separation provide a route to understanding the switching properties and concentration dependence of donor-acceptor Stenhouse adducts (DASAs). Through solvatochromic analysis of the open-form DASA in conjunction with X-ray diffraction and computational theory, we have analyzed the ionic character of a series of DASAs. First- and third-generation architectures lead to a higher zwitterionic resonance contribution of the open form and a zwitterionic closed form, whereas the second-generation architecture possesses a less charge-separated open form and neutral closed form. This can be correlated with equilibrium control and photoswitching solvent compatibility. As a result of the high contribution of the zwitterionic resonance forms of first- and third-generation DASAs, we were able to control their switching kinetics by means of ion concentration, whereas second-generation DASAs were less affected. Importantly, these results show how the previously reported concentration dependence of DASAs is not universal, and that DASAs with a more hybrid structure in the open form can achieve photoswitching at high concentrations.

DID it or DIDn't it? Exploration of a failure to replicate binge-like alcohol-drinking in C57BL/6J mice.

We previously reported that commercially-sourced C57BL/6J (B6) male mice with a history of adult-onset binge-drinking exhibit anxiety-like behavior in early withdrawal, while the negative affective state incubates during protracted withdrawal in adolescent-onset binge-drinking males. As the results of such studies are potentially confounded by age-related differences in reactivity to environmental stress, we employed a 2-bottle-choice DID procedure (20 and 40% alcohol; 20 min habituation to the drinking cage) to examine the effects of binge-drinking on negative affect in male and female, adult and adolescent, B6 mice from our university colony. Unexpectedly, the mice in the initial experiment exhibited very low alcohol intake, with little sign of withdrawal-induced negative affect. This failure to replicate prompted us to examine how the duration of drinking cage habituation, the number of alcohol concentrations presented and the animal source might influence the propensity to binge-drink. Herein, we show that both male and female adult mice from our colony will binge-drink when allowed 45 min to habituate to the drinking cages, irrespective of whether mice are offered a choice between 2, 3 or 4 alcohol concentrations. Further, when drinking under 4-bottle-choice procedures (5, 10, 20 and 40% alcohol), adult-onset binge-drinking females exhibit robust negative affect in early withdrawal akin to that reported previously for adult males; however, the negative affective state persists for at least 30 days into withdrawal. Also unlike males, adolescent-onset binge-drinking females exhibit some signs of negative affect, as well as potentiated alcohol intake, in early withdrawal, which persist into later withdrawal. These latter data suggest that the age-related differences in the temporal patterning of the negative affective state produced by alcohol withdrawal may vary as a function of sex, which may have implications for understanding sex differences in the etiology of affective disorders and alcoholism co-morbidity.