Evidence for sex-specific selection in brain: a case study of the nine-spined stickleback.

Theory predicts that the sex making greater investments into reproductive behaviours demands higher cognitive ability, and as a consequence, larger brains or brain parts. Further, the resulting sexual dimorphism can differ between populations adapted to different environments, or among individuals developing under different environmental conditions. In the nine-spine stickleback (Pungitius pungitius), males perform nest building, courtship, territory defence and parental care, whereas females perform mate choice and produce eggs. Also, predation-adapted marine and competition-adapted pond populations have diverged in a series of ecologically relevant traits, including the level of phenotypic plasticity. Here, we studied sexual dimorphism in brain size and architecture in nine-spined stickleback from marine and pond populations reared in a factorial experiment with predation and food treatments in a common garden experiment. Males had relatively larger brains, larger telencephala, cerebella and hypothalami (6-16% divergence) than females, irrespective of habitat. Females tended to have larger bulbi olfactorii than males (13%) in the high food treatment, whereas no such difference was found in the low food treatment. The strong sexual dimorphism in brain architecture implies that the different reproductive allocation strategies (behaviour vs. egg production) select for different investments into the costly brains between males and females. The lack of habitat dependence in brain sexual dimorphism suggests that the sex-specific selection forces on brains differ only negligibly between habitats. Although significance of the observed sex-specific brain plasticity in the size of bulbus olfactorius remains unclear, it demonstrates the potential for sex-specific neural plasticity.

Brain plasticity over the metamorphic boundary: carry-over effect of larval environment on froglet brain development.

Brain development shows high plasticity in response to environmental heterogeneity. However, it is unknown how environmental variation during development may affect brain architecture across life history switch points in species with complex life cycles. Previously, we showed that predation and competition affect brain development in common frog (Rana temporaria) tadpoles. Here, we studied whether larval environment had carry-over effects in brains of metamorphs. Tadpoles grown at high density had large optic tecta at metamorphosis, whereas tadpoles grown under predation risk had small diencephala. We found that larval density had a carry-over effect on froglet optic tectum size, whereas the effect of larval predation risk had vanished by metamorphosis. We discuss the possibility that the observed changes may be adaptive, reflecting the needs of an organism in given environmental and developmental contexts.

Predation- and competition-mediated brain plasticity in Rana temporaria tadpoles.

An increasing number of studies have demonstrated phenotypic plasticity in brain size and architecture in response to environmental variation. However, our knowledge on how brain architecture is affected by commonplace ecological interactions is rudimentary. For example, while intraspecific competition and risk of predation are known to induce adaptive plastic modifications in morphology and behaviour in a wide variety of organisms, their effects on brain development have not been studied. We studied experimentally the influence of density and predation risk on brain development in common frog (Rana temporaria) tadpoles. Tadpoles grown at low density and under predation risk developed smaller brains than tadpoles at the other treatment combinations. Further, at high densities, tadpoles developed larger optic tecta and smaller medulla oblongata than those grown at low densities. These results demonstrate that ecological interactions - like intraspecific competition and predation risk - can have strong effects on brain development in lower vertebrates.

Predation mediated population divergence in complex behaviour of nine-spined stickleback (Pungitius pungitius).

The proximate and ultimate explanations for behavioural syndromes (correlated behaviours--a population trait) are poorly understood, and the evolution of behavioural types (configuration of behaviours--an individual trait) has been rarely studied. We investigated population divergence in behavioural syndromes and types using individually reared, completely predator- or conspecific-naïve adult nine-spined sticklebacks (Pungitius pungitius) from two marine and two predatory fish free, isolated pond populations. We found little evidence for the existence of behavioural syndromes, but population divergence in behavioural types was profound: individuals from ponds were quicker in feeding, bolder and more aggressive than individuals from marine environments. Our data reject the hypothesis that behavioural syndromes exist as a result of genetic correlations between behavioural traits, and support the contention that different behavioural types can be predominant in populations differing in predation pressure, most probably as a result of repeated independent evolution of separate behavioural traits.

Adaptive brain size divergence in nine-spined sticklebacks (Pungitius pungitius)?

Most studies seeking to provide evolutionary explanations for brain size variability have relied on interspecific comparisons, while intraspecific studies utilizing ecologically divergent populations to this effect are rare. We investigated the brain size and structure of first-generation laboratory-bred nine-spined sticklebacks (Pungitius pungitius) from four geographically and genetically isolated populations originating from markedly different habitats. We found that the relative size of bulbus olfactorius and telencephalon was significantly larger in marine than in pond populations. Significant, but habitat-independent population differences were also found in relative brain and cerebellum sizes. The consistent, habitat-specific differences in the relative size of bulbus olfactorius and telencephalon suggest their adaptive reduction in response to reduced (biotic and abiotic) habitat complexity in pond environments. In general, the results suggest that genetically based brain size and structure differences can evolve relatively rapidly and in repeatable fashion with respect to habitat structure.

Similarities and dissimilarities of newborn and adolescent rats in the binding capacity of thymic glucocorticoid receptors.

The glucocorticoid receptor of the newborn thymus binds dexamethasone with the same specificity, as the adult ones. The best competitors of dexamethasone on the glucocorticoid receptor are dexamethasone itself and mifepristone (RU486). Estradiol can compete with dexamethasone on the glucocorticoid receptor. This is true in the case of newborn or adolescent thymus alike. Allylestrenol can slightly compete with dexamethasone on the glucocorticoid receptor in newborn, however this does not occur in adolescents. The other ligands - causing imprinting or imprinting like phenomenon earlier -- as tocopherol, menadione, retinoic acid, vitamin D(3) -- do not compete in vitro with dexamethasone on the thymic glucocorticoid receptor in newborn and adolescent animals. Possibilities of imprinting mechanism, considering the results are discussed.

Correlation between red cell and free plasma phenytoin levels in renal disease.

Free phenytoin levels were determined in a group of patients with renal disease treated by hemodialysis or transplantation and in epileptic patients who were otherwise healthy. A highly significant correlation was observed between free drug levels and the phenytoin content of red blood cells in both groups. Considerable fluctuation in free phenytoin levels was observed during long-term maintenance hemodialysis. After transplantation, the degree of abnormality in plasma protein binding was not related to the functional adequacy of the cadaveric allografts. Free phenytoin levels must be monitored in patients with renal disease.

Hemodialysis for methanol intoxication.

We describe nine patients with methyl alcohol poisoning who were treated with hemodialysis. The time from ingestion to dialysis varied from 4 to 100 hours. Predialysis blood methanol levels ranged from 3 to 570 mg/dl. All patients were acidotic and had an increased anion gap. Two patients died, seven recovered, but three had permanent visual impairment. There was little correlation between the blood methanol level or anion gap and visual outcome. The interval from ingestion to treatment appears to be more important than the initial biochemical status. We recommend prompt hemodialysis if the blood methanol level is above 50 mg/dl, when an amount of methanol exceeding the minimal lethal dose (30 ml) is known to have been ingested, when there is evidence of acidosis or when an abnormality has developed in vision, funduscopic examination or mental state. Concurrent therapy with alkali and ethanol is vital.

Management of uremic pericarditis: a report of 11 patients with cardiac tamponade and a review of the literature.

Uremic pericarditis remains a significant cause of morbidity and mortality in most hemodialysis programs. A review of the literature and out own experience show that uremic pericarditis should be vigorously treated when detected. Usually an increase in the dialysis program with regional heparinization is sufficient to control the pericarditis. When signs of pericardial effusion are manifested, patients often progress rapidly to cardiac tamponade. A surgical anterolateral pericardiectomy is the most satisfactory measure in controlling pericardial effusion and preventing fatal cardiac tamponade. Although these patients have severely impaired renal function, the operation can be performed safely with a low morbidity and mortality.

Effect of neonatal treatment with mifepristone or tamoxifen on the binding capacity of the thymic glucocorticoid or uterine estrogen receptor of adult rats: data on the mechanism of hormonal imprinting.

For studying the mechanism of perinatal hormonal imprinting newborn rats were treated with a single injection of the antihormones, mifepristone (RU486) or tamoxifen (100 microg each). Glucocorticoid receptors of thymi of 6 weeks old male and female, and uterine estrogen receptors of 2 months old female rats were studied for dexamethasone or estradiol binding, respectively. Tamoxifen caused faulty imprinting both in the thymic and uterine receptors, increasing affinity and density of males, and decreasing females' glucocorticoid receptors as well, as decreasing the density of uterine estradiol receptors. Neonatal mifepristone treatment was indifferent to the thymus, and decreasing to density of uterine estrogen receptors. Males' body weight significantly decreased 6 weeks after tamoxifen treatment. The results suggest that imprinting can not be provoked by a molecule (hormone antagonist) which can bind to the receptor without any postreceptorial events (mifepristone/glucocorticoid receptor), in the presence of some postreceptorial effects the reaction takes place, however the strongest reaction can be observed by the hormone analogue (tamoxifen) with postreceptorial (agonist) effect, not considering that the receptor is the direct target of the molecule or a cross-reaction is present.

Neonatal vitamin E treatment induces long term glucocorticoid receptor changes: an unusual hormonal imprinting effect.

Single neonatal vitamin E treatment significantly altered the affinity (Kd) of thymic glucocorticoid receptors in male adolescent and adult rats. In six weeks old animals the affinity increased (and there is a tendency for an increase in receptor density), in twelve weeks old animals the affinity decreased. The thymic glucocorticoid receptors and uterine estrogen receptors of female animals were not influenced at all. Thousandfold tocopherol did not compete with labeled dexamethasone for their receptors, suggesting that neonatal vitamin E imprinting effect was not done at direct receptorial level.

Effect of single neonatal vitamin K1 treatment (imprinting) on the binding capacity of thymic glucocorticoid and uterine estrogen receptors of adolescent and adult rats.

Neonatal single treatment with vitamin K1 (50 microg/animal) significantly increased the density (Bmax) of thymic glucocorticoid receptors of the adolescent (6 weeks old) and uterine estrogen receptors of adult (10 weeks old) females. The same tendency was observed in the thymus of males and adult females, however without significance. Receptor affinity was (not significantly) influenced in the same direction. Considering that the steroid receptor imprinting effect of vitamins A and D as well as the imprinting-like effect of vitamin E was demonstrated earlier, the ability for neonatal steroid receptor imprinting of the whole lipid-soluble vitamin group is now justified.

Effect of contraceptive treatment on thymic glucocorticoid receptors and hepatic microsomal enzyme system of adult rats.

Contraceptive steroid treatment accounted for about a 30 per cent decrease in the number of thymic glucocorticoid receptors of adult rats. Neonatal allylestrenol treatment had no influence on that treatment. The activity of the hepatic microsomal (PSMO) enzyme system was not changed by the contraceptive treatment. It appears that contraceptive treatment may account for overlaps on receptors in adulthood.

Hormonal imprinting: neonatal treatment of rats with the peroxysome proliferator clofibrate irreversibly affects sexual behaviour.

In the rat, the peroxysome proliferator activated receptor (PPAR) inducer clofibrate can moderately influence the hormone (testosterone) level and, after single perinatal treatment, irreversibly affects sexual behavior through the mechanism of hormonal imprinting. The thymic glucocorticoid and estrogen receptors weren't significantly influenced. The experiments call the attention to the universality of false imprinting by molecules able to bind to the steroid/thyroid receptor superfamily, and point to the different sensitivity to different ligands.

Intraosseous lipomatosis. A case report.

We report a case of systemic intraosseous lipomatosis involving the proximal femur, both ends of the tibia, and the tarsal and metatarsal bones. The lesions progressed during a five-year follow-up with a pathological fracture of the tibial plateau. CT scans were characteristic and helpful in diagnosis but MR imaging added little information. Intraosseous lipomatosis is a hamartomatous malformation due to hyperplasia of adipose tissue, and is fundamentally different from solitary benign intraosseous lipoma. Management involves reconstruction of any pathological fracture. Large progressive lesions should be treated by curettage and grafting in an attempt to prevent such fractures.

Effect of a single neonatal treatment with steroid hormone or steroid-like molecules on myocardial ouabain binding in the adult rat.

A single neonatal treatment of rats with vitamin D3, gibberellin, allylestrenol or diethylstilbestrol (DES) influenced the ouabain binding capacity of myocardial Na, K-dependent ATP-ase. Of the active molecules tested, vitamin D3, DES and gibberellin had appreciable impact on myocardial ouabain receptors, enhancing and depressing their activity, respectively. The thymic dexamethasone and uterine estrogen receptors did not alter their binding capacity in response to neonatal exposure to vitamin D3 or gibberellin.

Routine clinical applications of hemodialysis-hemoperfusion in chronic renal failure: case reports.

Five hemodialysis patients were treated with combined hemodialysis-hemoperfusion with their conventional hemodialyzer plus a 70-gram ultrathin collodion coated activated charcoal device for a total of 63 months. Indications for this therapy included pericarditis, peripheral neuropathy, clotting of conventional hemodialyzers and reduction of dialysis time and frequency. The outcome was beneficial in all cases and stable biochemical and hematological parameters were maintained. No increase in heparin requirements was noted and the therapy was thought to be cost-effective.

Effect of a single treatment (imprinting) with genistein or combined treatment with genistein+benzpyrene on the binding capacity of glucocorticoid and estrogen receptors of adult rats.

Hormonal imprinting takes place perinatally at the first encounter between the hormone and its target receptor. This is needed for the normal finishment of the maturation of the receptor-signal transduction system. In excess of foreign molecules, which can also bind to the receptor, faulty imprinting develops with life-long consequences. Genistein, a soybean phytosteroid (isoflavone), has estrogen-like effects and can be bound by steroid receptors. In the present experiments, single neonatal treatment (imprinting) with 20 microg of genistein, or combined treatment with 20 microg of genistein+20 microg of benzpyrene was done and liver and thymus glucocorticoid receptors of adult male and female rats and uterine estrogen receptors were studied. There was no difference in the binding capacity of uterine estrogen receptors. Genistein treatment alone caused a significant reduction of liver glucocorticoid receptor density in males; however, there were no other significant alterations. After combined genistein+benzpyrene treatment, more.than half of the thymus and liver glucocorticoid receptor values significantly changed. The results call attention to the imprinting-modifying effect of a second (environmental) imprinter.

Transgenerational effect of a single neonatal benzpyrene treatment on the glucocorticoid receptor of the rat thymus.

Hormonal imprinting is provoked perinatally by the appropriate hormone on its receptor, causing a life-long adjustment of the connection between the two participants. Faulty imprinting is caused by the presence of molecules similar to the hormone in this critical period, which results in a persistent alteration of the receptor. In the present experiment the transgenerational imprinting effect of a steroid-like environmental pollutant, benzpyrene, on the receptor binding capacity of filial thymic dexamethasone and uterine estrogen receptors was studied. The receptor density (Bmax) of the thymic glucocorticoid receptors of the males was reduced up to the third (F2) generation. In females this reduction was observed only in the F1 generation of treated animals. There was no change in receptor affinity (Kd). Uterine estrogen receptors were not subjected to transgenerational imprinting. The experiments demonstrate (1) the possibility of the transgenerational transmission of imprinting effect, (2) the differences of steroid receptors in different organs, and (3) the differences of male's and female's reactions from this aspect. The results call attention to the dangers of perinatal aromatic hydrocarbon exposition to the progeny generations.

[Penetration of cefbuperazone, a new cephamycin antibiotic, into human peritoneal exudate].

Pharmacokinetic studies were carried out on cefbuperazone ( CBPZ ) in 9 patients undergoing postoperative drainage. The concentration of CBPZ in serum and peritoneal exudate after one shot intravenous administration of 1 g was measured by bioassay and calculated respectively by two- and one-compartment open model. The results obtained were as follows: The pharmacokinetic parameters calculated from the serum levels were compared to those reported previously; T1/2 = 101 min., Vd = 4.06 L and Cl = 76 ml/min. The simulation curve of the peritoneal exudate level fit fairly with the mean values of 6 patients. It appeared that CBPZ penetrated somewhat slowly into peritoneal exudate with the peak value of 27.05 micrograms/ml at about 1 hour after the administration. The exudate levels thereafter declined more slowly than the serum ones (T1/2 = 134 min.). IT was 6.2 micrograms/ml even at 6 hours after the administration.