Context Inflammatory cytokines or cytokine inducers can alter basal ganglia activity, including reducing responsiveness to rewarding stimuli that may be mediated by cytokine effects on dopamine function. Objectives To determine whether long-term administration of the inflammatory cytokine interferon alfa reduces the basal ganglia response to reward and whether such changes are associated with decreased presynaptic striatal dopamine function and altered behavior. Design Cross-sectional and longitudinal studies. Setting Outpatient research unit and neuroimaging facilities at Emory University, Atlanta, Georgia. Patients Medically stable adults with chronic hepatitis C virus (HCV) infection eligible for interferon alfa treatment. Main Outcome Measures Neural activity in the ventral striatum during a hedonic reward task as measured by functional magnetic resonance imaging, uptake and turnover of radiolabeled fluorodopa F 18 (18F-dopa) in caudate and putamen using positron emission tomography, and interferon alfa–induced depression, anhedonia, fatigue, and neurotoxicity. Results Patients with HCV receiving interferon alfa for 4 to 6 weeks (n=14) exhibited significantly reduced bilateral activation of the ventral striatum in the win vs lose condition of a gambling task compared with patients with HCV awaiting interferon alfa treatment (n=14). Reduced activation of the ventral striatum was, in turn, significantly correlated with anhedonia, depression, and fatigue. In a separate longitudinal study, patients with HCV treated with interferon alfa for 4 to 6 weeks (n=12) exhibited significantly increased 18F-dopa uptake and decreased 18F-dopa turnover in caudate and putamen and in the same ventral striatal regions identified in the functional magnetic resonance imaging study. Baseline and percentage change in 18F-dopa uptake and turnover were correlated with behavioral alterations, including depression, fatigue, and neurotoxicity, during interferon alfa administration. Conclusions These data replicate and extend findings that inflammatory stimuli, including inflammatory cytokines, such as interferon alfa, alter basal ganglia activity and behavior in association with significant changes in presynaptic striatal dopamine function consistent with decreased dopamine synthesis or release.

In this small patient sample, relative amino acid transport compared with renal cortex is elevated in renal papillary cell carcinoma but not in clear cell carcinoma.

The rhesus macaque (Macaca mulatta) is an important primate model for social cognition, and recent studies have begun to explore the impact of oxytocin on social cognition and behavior. Macaques have great potential for elucidating the neural mechanisms by which oxytocin modulates social cognition, which has implications for oxytocin-based pharmacotherapies for psychiatric disorders such as autism and schizophrenia. Previous attempts to localize oxytocin receptors (OXTR) in the rhesus macaque brain have failed due to reduced selectivity of radioligands, which in primates bind to both OXTR and the structurally similar vasopressin 1a receptor (AVPR1A). We have developed a pharmacologically-informed competitive binding autoradiography protocol that selectively reveals OXTR and AVPR1A binding sites in primate brain sections. Using this protocol, we describe the neuroanatomical distribution of OXTR in the macaque. Finally, we use in situ hybridization to localize OXTR mRNA. Our results demonstrate that OXTR expression in the macaque brain is much more restricted than AVPR1A. OXTR is largely limited to the nucleus basalis of Meynert, pedunculopontine tegmental nucleus, the superficial gray layer of the superior colliculus, the trapezoid body, and the ventromedial hypothalamus. These regions are involved in a variety of functions relevant to social cognition, including modulating visual attention, processing auditory and multimodal sensory stimuli, and controlling orienting responses to visual stimuli. These results provide insights into the neural mechanisms by which oxytocin modulates social cognition and behavior in this species, which, like humans, uses vision and audition as the primary modalities for social communication.

Purpose We prospectively evaluated the amino acid analogue positron emission tomography radiotracer anti-3-[18F]FACBC compared to ProstaScint® (111In-capromab pendetide) single photon emission computerized tomography-computerized tomography to detect recurrent prostate carcinoma. Materials and Methods A total of 93 patients met study inclusion criteria who underwent anti-3-[18F]FACBC positron emission tomography-computerized tomography plus 111In-capromab pendetide single photon emission computerized tomography-computerized tomography for suspected recurrent prostate carcinoma within 90 days. Reference standards were applied by a multidisciplinary board. We calculated diagnostic performance for detecting disease. Results In the 91 of 93 patients with sufficient data for a consensus on the presence or absence of prostate/bed disease anti-3-[18F]FACBC had 90.2% sensitivity, 40.0% specificity, 73.6% accuracy, 75.3% positive predictive value and 66.7% negative predictive value compared to 111In-capromab pendetide with 67.2%, 56.7%, 63.7%, 75.9% and 45.9%, respectively. In the 70 of 93 patients with a consensus on the presence or absence of extraprostatic disease anti-3-[18F]FACBC had 55.0% sensitivity, 96.7% specificity, 72.9% accuracy, 95.7% positive predictive value and 61.7% negative predictive value compared to 111In-capromabpendetide with10.0%, 86.7%, 42.9%, 50.0% and 41.9%, respectively. Of 77 index lesions used to prove positivity histological proof was obtained in 74 (96.1%). Anti-3-[18F]FACBC identified 14 more positive prostate bed recurrences (55 vs 41) and 18 more patients with extraprostatic involvement (22 vs 4). Anti-3-[18F]FACBC positron emission tomography-computerized tomography correctly up-staged 18 of 70 cases (25.7%) in which there was a consensus on the presence or absence of extraprostatic involvement. Conclusions Better diagnostic performance was noted for anti-3-[18F]FACBC positron emission tomography-computerized tomography than for 111In-capromab pendetide single photon emission computerized tomography-computerized tomography for prostate carcinoma recurrence. The former method detected significantly more prostatic and extraprostatic disease.

Low. et ( I / and crystallized from MeOH-H20 to yield 2.58 g (56% yield) of 10: mp 155-158"; nmr 6 5.64 (s, -CH=CH-). The mass spectrum showed the molecular ion a t m/e 703. Anal ( C~J H B~N O~~) C, H, N.Erythronolide A Oxime (11). A solution of 22.55 g (0.032 mol) of 10 in 1.5 1. of 3% HCl in MeOH was left a t room temperature for 21 hr. The MeOH was removed in ~'acu.0, EtOAc was added to the residue, and the solution was washed with dilute NaHC03. After drying, the solution was stirred briefly with charcoal, filtered, and concentrated to dryness. TIC revealed a major spot much slower moving than 10, several minor impurities, and two fast moving spots. Two crystallizations from (CH&CO-C&4 gave 9.64 g (69% yield) of pure 11: m p 236-239"; ir 1710 cm (lactone). The mass spectrum showed the molecular ion a t m j e 3,5-Diacetylerythronolide A Acetoxime (12). To 0.300 g (0.69 mmol) of 11 dissolved in 6 ml of anhydrous CJHJN was added 1.2 ml (12 mmol) of Ac2O and the solution was heated a t 70" for 16 hr. Solvent was removed using an oil pump, and the residue was dissolved in EtOAc and washed with dilute NaHC03. After drying, the solution was concentrated in vacuo to a solid residue. Crystallization from CHZC12-Et20 provided 0.302 g (77% yield) of pure 12: mp 234-235"; nmr 6 2.08, 2.11, and 2.20 (acetyl methyls); [a]Z5D -51.2" (c 0.97, CHC13). The mass spectrum showed the molecular ion a t m/e 559. Anal. (C27H45NOll) C, H, N. Erythronolide A (13). To a solution of 0.303 g (0.7 mmol) of 11 in 15 ml of MeOH was added 2.4 g (35 mmol) of NaN02 in 10 ml of H2O. After cooling in an ice bath, 35 ml (35 mmol) of 1 N HCI was added dropwise with stirring over 15 min. The solution was left at 3" for 5.5 hr and made basic with saturated NaHC03, and most of the MeOH was removed in L~C U O . The product was extracted with CHC13; the extract was dried and concentrated to a foam. Three crystallizations from ( C H~) Z C O -C~H~~ gave 0.115 g (40% yield) of pure 13: mp 172-173": ir 1712 (lactone) and 1688 cm (ketone); hmaxEfoH 290 nm ( e 37). The mass spectrum did not give a molecular ion peak but instead gave a peak for M--18at mle400. A n d . (C21H3808) C, H.A variety of Hantzsch-type dihydropyridines and related compounds have been prepared in the course of a structureactivity study of these potent hypotensive agents. The biological activity of one of these compounds (Ib) is described. This compound may be exerting its cardiovascular effects through a direct action on vascular smooth muscle. In comparative tests with hydralazine, a clinically used vasodilator, the effects of hydralazine tended to decrease over the treatment period, whereas Ib did not show this same tendency.