Effect of morphine and nalmefene on energy balance in diabetic and non-diabetic rats

Male rats made diabetic by intravenous injection of streptozotocin were used to evaluate the effect of the diabetic state on morphine- and nalmefene-induced changes in food intake and body weight. Morphine increased 4 hour food intake in non-diabetic rats after an initial injection, but increased intake in diabetic rats only after repeated injections. Unlike short term measurements, morphine decreased food intake when measured over 24 or more hours in both groups. Chronic injection of morphine decreased body weight only in non-diabetic rats. Feed efficiency data suggest that morphine had a more potent effect on energy balance in the non-diabetic rats. The opioid antagonist, nalmefene, did not alter body weight in either group and only altered food intake in the diabetic animals. These data are in concert with other reports indicating that the diabetic state renders animals less responsive to the effects of morphine on nociception and smooth muscle contraction.     

Central administration of the opioid antagonist, LY255582, decreases short- and long-term food intake in rats.

A variety of opioid antagonists have been reported to decrease short-term food intake, but few appear to reduce long-term intake. In the present study we evaluated the effect of a relatively new class of opioid antagonists, 3,4-dimethyl-4-phenylpiperidines, on short-term and long-term food intake after central administration. We also evaluated their affinities for the mu and kappa opioid receptor sites in synaptosomal membranes derived from rat whole brain tissue (minus cerebellum) and guinea-pig cortex, respectively. The affinities for the mu receptor sites were LY255582 greater than LY217273 greater than LY256897 greater than naloxone greater than LY227444. The affinities for the kappa receptor sites were LY255582 greater than LY256897 = LY217273 greater than LY227444. LY255582 reduced food intake for up to 24 h after a single intraventricular injection. Doses as low as 1 microgram of LY255582 decreased food intake for up to 4 h. All other drugs were much less powerful. Naloxone and LY256897 only decreased food intake after injection of the 100 microgram dose. LY227444 and LY217273 failed to decrease intake at all doses tested. LY255582 (100 micrograms) decreased food intake over a 7 day period when injected intraventricularly once per day. The body weight of the rats also decreased during the 7 day period. Upon cessation of drug administration body weights and food intake approached control levels. Thus, LY255582 appears to be a very potent and long-acting anorectic agent which may be useful in the treatment of obesity. The mu and kappa binding profile of the phenylpiperidines does not seem to clearly correlate with their anorectic activity.     

Murine pregnancy-associated modulations in lymphocyte reactivity to mitogens: identification of the cell populations affected

Lymphocytes from the thymus, spleen and inguinal lymph nodes of syngeneically pregnant and non-pregnant mice were compared in their responsiveness to polyclonal stimulation by mitogen. Pregnancy-associated changes in mitogen reactivity were detected, on a cell-per-cell basis, in thymocytes (increased) and spleen cells (decreased) but not in lymph node cells. The hyperreactivity of thymocytes during pregnancy correlated with physiological involution of the thymus occurring through the selective loss of relatively immature, non-mitogen-reactive, Lyt 1+2+ cells. The remaining cells were found largely to be mature Lyt 1+2- T cells with the capacity to respond to mitogenic stimulation. It is most likely the relative increase in the proportion of these Lyt 1+2- cells that causes the hyper-responsiveness of thymocytes to mitogens observed during pregnancy. On the other hand, while spleen cells from pregnant animals gave lower responses to mitogens than those from control virgin females, isolated splenic T cells from the two groups proved equally reactive to T cell mitogens. This supports the contention that at least some aspects of immunity during pregnancy are down-regulated by inhibitory cells within the non-T cell compartment. The results demonstrate the importance of identifying the reactive cell population in studies on changes in lymphocyte responsiveness in pregnancy.     

Intra-amygdalar injection of DAMGO: effects on c-Fos levels in brain sites associated with feeding behavior

It is well known that the mu opioid agonist, Tyr-D-Ala-Gly-(me) Phe-Gly-ol (DAMGO), increases food intake in rats when injected into a variety of brain sites including the central nucleus of the amygdala (CeA). Immunohistochemical studies measuring c-Fos immunoreactivity (IR) suggest that the CeA contributes to opioid-related feeding. In the current study, we injected 2 nmol of DAMGO and measured food intake, c-Fos IR levels in various brain sites involved in feeding behavior, and mu opioid receptor internalization. We also studied the effect of CeA-injected DAMGO on LiCl-induced increases in c-Fos IR in the amygdala. As was expected, intra-CeA injection of DAMGO increased food intake of rats over a 4-h period. DAMGO injection into the CeA also resulted in mu opioid receptor internalization in the CeA, indicating activation of mu opioid receptor expressing neurons in this site. Administration of DAMGO into the CeA increased c-Fos IR levels in the shell of the nucleus accumbens (NAcc), but not in 17 other brain sites that were studied. We also found that intra-CeA injection of DAMGO, prior to LiCl injection, decreased c-Fos IR levels in the CeA compared to vehicle-injected rats. Thus, intra-CeA administration of DAMGO may increase feeding, in part, by activating neurons in the shell of the nucleus accumbens and by inhibiting activity of selected neurons in the CeA.     

In vitro activity of cefsulodin against multi-resistant isolates of Pseudomonas aeruginosa.

Clinical isolates of Pseudomonas aeruginosa from 245 patients with different infections were tested to determine their in vitro susceptibility to cefsulodin and other anti-pseudomonad antibiotics. Cefsulodin inhibited 90% of the isolates as compared with 89% by ceftazidime, 84% by piperacillin and 73% by ticarcillin. Of the three aminoglycosides used, gentamycin (60%) and netilmycin (77%) were less inhibitory. Amikacin was the most active, inhibiting 92% of the clinical isolates. Over 60% of the isolates resistant to ticarcillin and piperacillin were susceptible to cephalosporin and aminoglycosides used. Among cefsulodin-resistant isolates, ceftazidime was active against 67% and amikacin and netilmycin against 71% of isolates. Sixty percent of ceftazidime-resistant strains were susceptible to cefsulodin.