Dietary NaC1 during pregnancy and lactation: effect on brain angiotensin II receptors and behavior

Female rats were fed diets containing either a basal (0.12%), mid- (1%) or high (3%) level of NaCl during pregnancy and lactation. Plasma aldosterone was elevated approximately 5- and 15-fold in dams fed basal compared with either the mid- or high-NaCl diets at the end of both pregnancy and lactation (Postnatal Day 21), respectively. Dams fed basal diet and killed at the end of lactation had a higher density of angiotensin II receptors in the organum vasculosum laminae terminalis, paraventricular hypothalamus, and median preoptic nucleus than did rats fed either mid- or high-NaCl diets. Other dams, treated identically, were returned to rodent chow (approximately 0.2% NaCl) at the end of lactation for intake tests during the next week. Dams that had received basal diet did not differ from mid-NaCl and high-NaCl groups in sodium appetite induced by either acute sodium depletion or mineralocorticoid administration but showed the lowest spontaneous intake of NaCl solution.     

A comparison of the analgesic efficacy of 0.25% levobupivacaine combined with 0.005% morphine, 0.25% levobupivacaine alone, or 0.005% morphine alone for the management of postoperative pain in patients undergoing major abdominal surgery

We compared the relative efficacy of the combination of the single-isomer local anesthetic levobupivacaine and the opioid analgesic morphine versus both drugs alone for postoperative epidural analgesia after major abdominal surgical procedures. Thoracic epidural anesthesia was produced and maintained with levobupivacaine 0.75% in combination with general inhaled anesthesia without opioids. Patients were randomized to one of three postoperative treatment groups: 1) a combination of levobupivacaine 0.25% and morphine 0.005%; 2) levobupivacaine 0.25%; or 3) morphine 0.005%. Postoperatively, all epidural infusions were commenced at a rate of 4 mL/h. Patients could receive a 4 mL-bolus dose and an increase in the epidural infusion rate by 2 mL/h on request for supplemental analgesia. Patients were also allowed ketorolac as a supplemental analgesic at any time after the first analgesic request. Patients in the combination group had longer times to request for supplemental analgesia as compared with the levobupivacaine only group (P < 0.05) and a trend toward longer time to request as compared with the morphine only group (P = 0.066). Patients in the combination group had lower visual analog scale pain scores at rest and activity at 4 and 8 h and fewer requests for supplemental ketorolac (P < 0.05). In conclusion, this study demonstrates a significant improvement in postoperative analgesic efficacy with the combination of levobupivacaine and morphine for continuous epidural analgesia after major abdominal surgical procedures. IMPLICATIONS: A significant improvement in postoperative analgesic efficacy is demonstrated with the thoracic epidural administration of the combination of the single-isomer local anesthetic levobupivacaine 0.25% and morphine 0.005% in patients after major abdominal surgical procedures as compared with either drug used alone.     

Relative medial and dorsal cortex volume in relation to foraging ecology in congeneric lizards

The need to locate distributed resources such as mates, food, and nests is correlated with an enlarged hippocampus in many mammalian and avian species. This correlation is believed to be a consequence of selection for spatial ability. Little is known about how such ecological needs affect non-mammalian, non-avian species. In lizards, the putative hippocampal homologues are the dorsal cortex (DC) and medial cortex (MC). We examined the relationship between foraging ecology and the size of the DC and MC in congeneric male lizards. We predicted based on the mammalian and avian literature that Acanthodactylus boskianus, an active forager that captures clumped, immobile prey would have a larger MC and DC than A. scutellatus, a sit-and-wait predator, that captures mobile prey. Our previous behavioral studies showed that A. boskianus did not differ from A. scutellatus on a spatial task but that A. boskianus was significantly better at the reversal of a visual discrimination, another task that is hippocampally dependent in mammals. In the current study, we found that, relative to telencephalon volume, the MC and DC were larger in the active forager whereas a control region, the lateral, olfactory, cortex, was similar in size between species. The current anatomical results suggest that MC and DC size is related to active foraging in lizards and, along with our previous behavioral studies, show that it is possible for this relationship to occur in the absence of evidence for species differences in spatial memory. Copyright (R) 2000 S.Karger AG, Basel     

Dibenzo[a,l]pyrene-induced DNA adduction, tumorigenicity, and Ki-ras oncogene mutations in strain A/J mouse lung

Dibenzo[a,l]pyrene (DB[a,l]P), an environmental polycyclic aromatic hydrocarbon, is the most potent carcinogen ever tested in mouse skin and rat mammary gland. In this study, DB[a,l]P was examined for DNA adduction, tumorigenicity, and induction of Ki-ras oncogene mutations in tumor DNA in strain A/J mouse lung. Groups of mice received a single i.p. injection of 0.3, 1.5, 3.0, or 6.0 mg/kg DB[a,l]P in tricaprylin. Following treatment, DNA adducts were measured at times between 1 and 28 days, while tumors were counted at 250 days and analyzed for the occurrence of point mutations in codons 12 and 61 of the Ki-ras oncogene. DB[a,l]P in strain A/J mouse lung induced six major and four minor DNA adducts. Maximal levels of adduction occurred between 5 and 10 days after injection followed by a gradual decrease. DB[a,l]P-DNA adducts in lung tissue were derived from both anti- and syn-11,12- dihydroxy-13,14-epoxy- 11,12,13,14-tetrahydrodibenzo[a,l]pyrene (DB[a,l]PDE) and both deoxyadenosine (dAdo) and deoxyguanosine (dGuo) residues in DNA as revealed by cochromatography. The major adduct was identified as a product of the reaction of an anti-DB[a,l]PDE with dAdo in DNA. DB[a,l]P induced significant numbers of lung adenomas in a dose- dependent manner, with the highest dose (6.0 mg/kg) yielding 16.1 adenomas/mouse. In tricaprylin-treated control animals, there were 0.67 adenomas/mouse. Based on the administered dose, DB[a,l]P was more active than other environmental carcinogens including benzo[a]pyrene. As a function of time-integrated DNA adduct levels, DB[a,l]P induced lung adenomas with about the same potency as other PAHs, suggesting that the adducts formed by DB[a,l]P are similar in carcinogenic potency to other PAHs in the strain A/J mouse lung model. Analysis of the Ki- ras mutation spectrum in DB[a,l]P-induced lung tumors revealed the predominant mutations to be G-->T transversions in the first base of codon 12, A-->G transitions in the second base of codon 12, and A-->T transversions in the second or third base of codon 61, concordant with the DNA adduct profile.      

Functional connectivity among limbic brain areas: differential effects of incubation temperature and gonadal sex in the leopard gecko, Eublepharis macularius

The neural basis of individual differences in behavior has been studied primarily by analyzing the properties of specific neural areas. However, because of the organization of the nervous system, it is also plausible that differences in behavior are mediated by differences in the interactivity or functional connectivity among brain nuclei in particular neural circuits. In the leopard gecko, Eublepharis macularius, the temperature of the egg during incubation not only determines gonadal sex, but also shapes the sociosexual behaviors, reproductive physiology, and hormone sensitivity of adult animals. In this study the effects of both incubation temperature and gonadal sex on functional connectivity among limbic brain areas were examined. Functional connectivity was assessed by analyzing covariance patterns in metabolic capacity, as revealed by quantitative cytochrome oxidase histochemistry. It was hypothesized that incubation temperature and gonadal sex affect the propensity to display aggressive or sexual behaviors by altering the functional connectivity within relevant neural circuits. The correlations of metabolic capacity between the anterior hypothalamus and both the septum and preoptic area were significant only in relatively aggressive individuals, suggesting that these circuits may regulate the phenotypic variation in aggressiveness caused by incubation temperature. The correlations between the ventromedial hypothalamus and both the dorsal ventricular ridge and septum were significant only in females, suggesting that these circuits may modulate female-typical sexual behaviors. Correlations among preoptic, hypothalamic and amygdalar areas tended to be distributed across both sexes, suggesting that there may be shared pathways underlying the expression of male-typical and female-typical behaviors.     

Hypothalamic arginine vasotocin mRNA abundance variation across sexes and with sex change in a coral reef fish

Gonadal hormones are important mediators of sexual and aggressive behavior in vertebrates. Recent evidence suggests that the peptide hormones arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin (AVP) often critically mediate these gonadal hormone effects on behavior and have direct influences on behavioral variation. Behavioral differences between sexes, across reproductive states, and even among closely related species are correlated with differences in central AVT/AVP systems in many species. We report differences in hypothalamic AVT mRNA levels between distinct alternate male phenotypes and with female-to-male sex change in the bluehead wrasse (Thalassoma bifasciatum), a teleost fish. The aggressively dominant and strongly courting male phenotype has greater numbers of AVT mRNA producing cells in the magnocellular preoptic area of the hypothalamus than females. Levels of AVT mRNA within these cells in dominant males are also approximately three times female levels whereas the non-aggressive male phenotype has AVT mRNA levels approximately twice female levels. Behavioral sex change is very rapid in this species and is not dependent on the presence of gonads. Conversely, rapid increases in sexual and aggressive behavior during sex change are closely paralleled by approximate fourfold increases in hypothalamic AVT-mRNA levels. The behavioral plasticity shown by bluehead wrasses in response to social environment might be mediated in part by a neuropeptide, AVT, with changes in the gonads and gonadal hormones as the result rather than the cause of behavioral dominance. Copyright (R) 2000 S. Karger AG, Basel     

Revisiting the sponge sources, stereostructure, and biological activity of cyclocinamide a

The dramatic biogeographical variations in the secondary metabolites from Psammocinia aff. bulbosa have complicated our efforts to reisolate the two most cytotoxic of its metabolites, (+)-psymberin and (+)-cyclocinamide A. Reported now are the results of a new study that demonstrates our ability to repeatedly isolate these two compounds through targeted collection efforts. Additional study of the new sample of (+)-cyclocinamide A has enabled finalizing its biological activity and absolute stereochemistry as 4S, 7S, 11S, 14S.