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PURPOSE/OBJECTIVE(S) The purpose of this analysis was to investigate whether the combination of external beam radiotherapy (EBRT) and brachytherapy boost (EBRT+BT) is superior to EBRT alone in terms of biochemical control (BC) in the management of intermediate (IR) and high risk (HR) prostate cancer (PC) patients and whether the difference is associated with local biologically effective dose (BED) escalation. MATERIALS/METHODS We investigated 1123 patients treated for IR (24.8%) or HR PC (75.2%) with EBRT (90.7%) or EBRT+BT (9.3%) at one institution between 2003 and 2012. Kaplan-Meier curves were used to calculate biochemical control. Log-rank testing and Cox regression were used to compare results between groups. BED was calculated using α/β of 3 for PC. The majority of patients treated with EBRT received 76 Gy in 2 Gy fractions (79%, median BED = 126.7 Gy) or equivalent. The majority of patients treated with EBRT+BT received either 54 Gy in 2 Gy fractions followed by 10-11 Gy single fraction BT boost (47.6%, median BED = 133.3 Gy), or 46-50 Gy in 2 Gy fx followed by 20-21 Gy two fraction BT boost (51.4%, median BED = 171.2 Gy). RESULTS The median age of the patients was 68-years. The 5-year BC was 79%. There was no statistically significant difference in BC between patients treated with EBRT or BT in IR (P = 0.74) and HR (P = 0.73) PC groups. There was a significant difference between patients receiving lower and higher BED (> 135 Gy) fractionation schemes in favor of higher BED, both for IR (5-y BC of 100% vs 81%, P = 0.02) and HR group (5-y BC of 92% vs 77%, P = 0.02). The BED was inversely associated with risk of BC in univariate analysis (HR = 0.98; CI95% 0.97-0.99; P < 0.01), and remained an independent prognostic factor in the multivariate analysis (HR = 0.97; CI95% 0.96-0.99; P < 0.01) along with Gleason Grade Groups score (HR = 1.18; CI95% 1.05-1.32; P < 0.01). CONCLUSION The combination of EBRT and BT boost has the potential to significantly improve biochemical control in IR and HR prostate cancer patients through local BED escalation. The improvement in BC was observed in patients receiving higher BED, as well as a significant association between BED and risk of biochemical failure.

We present fluorescence emission spectra of the 2-tolunitrile dimer and the 2-tolunitrile water cluster through various vibronic bands in the electronically excited state. From the transition dipole moments in the individual monomers, the 2-TN dimer has shown to form J-aggregates, which is why the one-photon allowed transition is the S1 state in this cluster in contrast to other symmetric dimers, which tend to form H-aggregates. The changes of the molecular structures upon electronic excitation have been determined from a fit of the intensities in various fluorescence emission spectra. The excited state structure of the 2-TN dimer has been found to be asymmetric, in contrast to the ground state structure. Thus, emission takes place from one of the locally excited monomer moieties in the 2-tolunitrile dimer.

Regardless of whether you are a commercial truck driver performing a job, a patient driving to get her medicine, or a citizen who just recreationally enjoys marijuana, the rules surrounding the transportation of marijuana are important. California became the first state to legalize the medical use of marijuana in 1996, and the prevalence of medical and recreational marijuana legalization has only expanded since then. At this point, some product or chemical compound from the cannabis plant is virtually everywhere in the United States, yet the transportation of these products has not been comprehensively debated by the public, let alone legislated. This article is focused on exploring the unique legal landscape surrounding the transportation of marijuana, hemp, and cannabidiol (CBD) from both a business and individual perspective. By showcasing examples of how businesses and individuals have been impacted by the unclarity in this area, the goal is to convey that nothing about transporting these products is risk-free and that there is unnecessary conflict between state and federal law.

Single vibronic level fluorescence spectra of the electronic origin and of seven vibronic bands between 0,0 and 0,0 + 1265 cm −1 have been measured and analyzed by means of a combined Franck–Condon/rotational constants fit. The rotational constants in ground and lowest electronically excited singlet state of four different isotopologues have been taken from previous rotationally resolved measurements of Schmitt et al. (2006). The intensities of 182 vibronic emission bands and of 8 rotational constants have been used for a fit of the complete heavy atom geometry changes upon electronic excitation. Vibronic modes, about 1000 cm −1 above the electronic origin, show strong deviations from Franck–Condon behavior in emission. Herzberg–Teller coupling contributes to this effect. 1300 cm −1 above the origin, we observe the onset of intramolecular vibrational redistribution in the emission spectra.

The actions of opioids are mediated by multiple types of opioid receptor. As a result, ‘obtaining the right balance' is the catchphrase most frequently heard these days in analgesic research laboratories throughout the pharmaceutical industry. Tomorrow's analgesics will feature a prominent κ component, a touch of δ, a tickle of μ, but not even a wisp of σ. New compounds are fashioned largely from structure-activity relationships involving bioassays and radioligand receptor binding. These in-vitro approaches have become well established over the past decade since they help to link receptor type to the analgesic under investigation. What about the complementary preclinical tests in-vivo ? Specifically, how can the animal pharmacologist assist in characterizing κ opioid activity? In this article, Alan Cowan and Debra E. Gmerek present a survey of tests that are being used to detect and define κ activity in-vivo . Special emphasis is placed on the rat bombesin-scratch test, a new procedure in which several κ-preferring agents are selectively active.

Reliable antipruritic agents that can be given systemically are not available at present. This may be due to the lack of animal models for screening such compounds. Bombesin, a tetradecapeptide originally isolated from frog skin, induces dose-related excessive scratching when administered intracerebroventricularly (i.c.v.) to rats. With the help of a microcomputer, we monitored the scratching elicited by a standard, submaximal dose of bombesin (0.10 μg, i.c.v.). This system provides 1) a sensitive and novel way of assessing drug-induced behavioral depression, and 2) a means of quantifying interactions between bombesin and possible antagonists. Thus, bombesin-induced grooming is antagonized by behaviorally nondepressant doses of methdilazine, trimeprazine, and chlorpromazine but not by morphine, haloperidol, diphenhydramine, hydroxyzine, mepyramine, cimetidine, or cyproheptadine. Methdilazine and trimeprazine are used clinically as antipruritic agents. The model therefore offers a means of evaluating new, systemic antipruritic agents, particularly those which may be active in treating histamine-independent pruritus.

The role of the pituitary-adrenal axis in the inhibition of gastrointestinal transit caused by intrathecal administration of bombesin was examined. Bombesin (0.3-10 micrograms) slowed transit by this route in a dose-related manner. Either hypophysectomy or adrenalectomy prevented the inhibition of gastrointestinal transit associated with bombesin (10 micrograms, i.th.). The inhibitory gut effects of this peptide were not prevented in sham-operated rats. Intrathecal bombesin-induced inhibition of gastrointestinal transit is thus dependent upon an intact pituitary-adrenal axis.

Centrally administered bombesin (0.1-3.5 micrograms, i.c.v.) inhibits gastrointestinal transit of a charcoal meal in a dose-related manner in rats. The roles of pituitary and adrenal glands in the mediation of this effect were assessed. The inhibition of gastrointestinal transit associated with bombesin (0.5 microgram, i.c.v.) was prevented by either hypophysectomy or adrenalectomy. Bombesin-induced inhibition of gastrointestinal transit is therefore mediated through the pituitary-adrenal axis. This is in contrast to bombesin-induced scratching and inhibition of gastric acid secretion which are not markedly influenced by either hypophysectomy or adrenalectomy.

The quantitative assessment of animal behavior by continuous or intermittent observation often requires much time and intense concentration. We have developed an accurate and convenient system which allows one observer to monitor up to four animals and record two types of behavior simultaneously. The system uses an inexpensive portable microcomputer including keyboard, video monitor, and cassette recorder. A program written in BASIC generates timed visible and audible cues, and tabulated data entered through the keyboard. The total number of occurrences of a particular behavior (e.g., "wet dog" shakes) and the frequency of a second behavior (e.g., grooming) may be measured. Frequency data, bases on intermittent observations, is processed for histogram display. The results may be copied from the video display or recorded on tape for further statistical analysis. The system has provided a convenient way to time experiments and collect data on drug-induced behavior in over 800 rats.

The mixed agonist-antagonist analgesics buprenorphine, butorphanol, nalbuphine, pentazocine and picenadol were compared to the prototype mu and kappa agonists morphine and Mr 2033, respectively, in the following tests in rhesus monkeys: overt behavioral effects upon acute administration in drug-naive animals; discriminative stimulus properties in monkeys trained to respond to either etorphine or ethylketazocine; self-administration of the test agent relative to codeine; single dose suppression and precipitation in withdrawn and non-withdrawn morphine-dependent monkeys, respectively; and primary addiction studies in drug-naive animals. Whereas both buprenorphine and nalbuphine precipitate withdrawal in morphine-dependent monkeys, withdrawal following chronic administration of buprenorphine resulted in no observable signs of abstinence, while nalbuphine withdrawal was similar to that seen in morphine-dependent monkeys. Butorphanol, pentazocine and picenadol all produced mild dependence of the kappa-type; that is, natural withdrawal behavior similar to that seen following chronic Mr 2033 administration.

We studied the in vivo pharmacology of ICI 154, 129, a new antagonist that is claimed to show selectivity for delta opiate receptors. At s.c. doses of 30 and 100 mg/kg, ICI 154, 129 had no marked effect on the gastrointestinal transit of a charcoal meal in mice. In this test, ICI 154, 129 reversed the inhibitory action of metkephamid (a proposed delta receptor agonist) but not that of levorphanol. ICI 154,129 was proconvulsant in the mouse picrotoxin potentiation test; the dose-response curve had a low ceiling and was biphasic. Naloxone (1 mg/kg, s.c.) enhanced the proconvulsant action of ICI 154, 129 (40 mg/kg, s.c.) by an unknown mechanism.

Intracerebroventricular (i.c.v.) injection of either morphine or bombesin to rats inhibits intestinal transit of an intraduodenally administered radiochromium marker. In this work, we show that tolerance develops to this effect of bombesin after i.c.v. infusion of the peptide (0.5 μg/h for 4 days via an s.c. implanted Alzet 2001 osmotic minipump). Tolerance also develops to the inhibition of intestinal transit associated with i.c.v. morphine after s.c. injections of morphine. Bombesin-induced delay of transit is not attenuated by naltrexone (10 mg/kg, s.c.), a standard narcotic antagonist. Nevertheless, two-way cross-tolerance develops between bombesin and morphine in this system. This is a surprising result since both bombesin and morphine are believed to act on different receptors and cause opposite effects on intestinal motility in rats.