Role of oxidative stress in the pathogenesis of septic ileus in mice.

We investigated the role of oxidative stress in the pathogenesis of septic ileus. Sepsis was induced by intraperitoneal (i.p.) injection of lipopolysaccharides (LPS, 20 mg kg(-1)) in mice. The effect of two i.p. injections of superoxide dismutase [polyethylene glycol (PEG)-SOD, 4000 U kg(-1)] and catalase (PEG-CAT, 15,000 U kg(-1)) was investigated on gastric emptying, intestinal transit and total nitrite plasma concentrations. We also performed immunohistochemical experiments on gastric and ileal tissue. LPS significantly delayed gastric emptying and intestinal transit while plasma nitrite levels increased. Polyethylene glycol (PEG)-SOD reversed the endotoxin-induced delay in gastric emptying and improved the delay in intestinal transit without effect on plasma nitrite levels. PEG-CAT slightly improved the delay in gastric emptying without effect on intestinal transit. Immunohistochemistry showed the presence of nitrotyrosine (NT) and 4-hydroxy-2-nonenal (HNE) in the gastric and ileal mucosa of LPS-treated mice. Treatment with PEG-SOD or PEG-CAT of LPS mice diminished the presence of NT or HNE in both tissues. In addition, LPS induced a significant increase in inducible nitric oxide synthase (iNOS)-positive residential macrophages in the external musculature of stomach and ileum, which significantly decreased after PEG-SOD or PEG-CAT treatment. The present results support a role for oxidative and nitrosative stress in the pathogenesis of septic ileus in mice.

In vitro activation of murine DRG neurons by CGRP-mediated mucosal mast cell degranulation.

Upregulation of CGRP-immunoreactive (IR) primary afferent nerve fibers accompanied by mastocytosis is characteristic for the Schistosoma mansoni-infected murine ileum. These mucosal mast cells (MMC) and CGRP-IR fibers, which originate from dorsal root (DRG) and nodose ganglia, are found in close apposition. We examined interactions between primary cultured MMC and CGRP-IR DRG neurons in vitro by confocal recording of intracellular Ca(2+) concentration ([Ca(2+)](i)). The degranulatory EC(50) for the mast cell secretagogue compound 48/80 (C48/80; 10 microg/ml) and the neuropeptides CGRP (2.10(-8) M) and substance P (SP; 3.10(-8) M) were determined by measurement of extracellular release of the granule chymase, mouse mast cell protease-1. Application of C48/80 (10 microg/ml) and CGRP and SP (both 10(-7) M) to Fluo-4-loaded MMC induced a transient rise in [Ca(2+)](i) after a lag time, indicative of mast cell degranulation and/or secretion. The CGRP response could be completely blocked by pertussis toxin (2 microg/ml), indicating involvement of G(i) proteins. Application of MMC juice, obtained by C48/80 degranulation of MMC, to Fluo-4-loaded DRG neurons induced in all neurons a rise in [Ca(2+)](i), indicative of activation. Degranulation of MMC by C48/80 in culture dishes containing Fluo-4-loaded DRG neurons also caused activation of the DRG neurons. In conclusion, these results demonstrate a bidirectional cross-talk between cultured MMC and CGRP-IR DRG neurons in vitro. This indicates that such a communication may be the functional relevance for the close apposition between MMC and CGRP-IR nerve fibers in vivo.

Effects of Schistosoma mansoni infection on somatostatin and somatostatin receptor 2A expression in mouse ileum.

Intestinal schistosomiasis is accompanied by motility-related dysfunctions but the underlying mechanisms are not well-known. Therefore, the presence and effects on intestinal contractility of somatostatin (SOM) and its receptor, SSTR2A, were investigated in the ileum of normal and infected mice. The distribution of SOM and SSTR2A was visualized using immunocytochemistry. Radioimmunoassay combined with oogram studies was performed to determine SOM levels and contractility measurements were determined in organ bath experiments. Schistosomiasis resulted in a significant decrease in somatostatin-positive endocrine cells, whereas the number of somatostatin-immunoreactive (IR) neuronal cell bodies did not change. From 8 weeks postinfection onwards, an increase was noted in somatostatin-IR nerve fibres in both villi and granulomas. The staining intensity for SSTR2A, expressed in somatostatin-negative myenteric cholinergic neurones, increased during infection suggesting an upregulation of this receptor. SOM levels were negatively correlated with the number of eggs during the acute phase, and were elevated during the chronic phase. Pharmacological experiments revealed that schistosomiasis diminished the inhibitory effect of SOM on neurogenic contractions. We can conclude that schistosomiasis influences the distribution and expression levels of SOM and SSTR2A in the murine ileum, which might explain the changed motility pattern.

Dimensions of maternal behaviour characteristics in domestic and wildxdomestic crossbred sows.

We examined the maternal behaviour of seven domestic and seven wildxdomestic primiparous sows during 10 days post partum to investigate two questions: (1) Did maternal behaviour change during domestication? (2) Can the interindividual variability of maternal behaviour be subsumed into a few dimensions of maternal temperament? We recorded: (a) willingness to leave the nest for food on Day 2; (b) reaction to a playback of squeezed piglet distress vocalisation on Day 2; (c) spontaneous nursing behaviour and spontaneous lying-down behaviour on Day 5 (from an overnight video recording); (d) reactions to playbacks of various piglet distress vocalisations on Day 6 and (e) reactions to a human in the 'nest' with piglets on Day 9. Moreover, data on baseline cortisol saliva concentration and its increase during a brief transportation period and novel environment challenge at the age of 5 months were available. Crossbred sows did not differ from domestic ones in any aspect of maternal behaviour except for a higher tendency to terminate final massage during nursings and a higher frequency of changing posture from lying to standing and back during the night. Factor analysis (based on correlation matrix of 11 behaviour and cortisol variables calculated for all 14 sows after removing the effect of breed) indicated that 82% of the variability in the data could be explained by three factors: first, 'calmness' on which low night time frequency of major posture changes, carefulness of lying-down behaviour and high propensity to remain in nursing position after milk ejection loaded positively while cortisol concentrations during challenge loaded negatively; second, 'protectiveness' with high loadings of the reaction scores to the playbacks of piglet distress calls and the human presence near the piglets; and third, 'nursing activity' which was strongly positively associated with nursing frequency, and negatively with the proportion of nutritive nursings and baseline cortisol values. The results indicate that most aspects of pig maternal behaviour have not been significantly changed by domestication and that substantial variability in maternal behaviour exists between sows, perhaps in the form of several behaviour characteristics which encompass both behaviour and endocrine profiles of the sows.

Statistical tomographic reconstruction: how many more iterations to go?

Single-photon emission tomography (SPET) is a popular, commonly used method to image the three-dimensional distribution of a radiopharmaceutical within the human body. In clinical studies, filtered back-projection (FBP) still seems to be the method of choice for tomographic reconstruction, although most manufacturers of gamma cameras include iterative statistical reconstruction methods in their basic software package. Quite a lot of progress in the development of these iterative methods has been made during the past few years and promising typical clinical examples have been shown. But there is still a need for a clinical comparison of the new and the old methods in patient studies. The processing time, even on state-of-the-art computer systems, may be the most prohibitive factor for using the more advanced iterative reconstruction methods including scatter and attenuation correction.

Poor rearing conditions and social stress in pigs: repeated social challenge and the effect on behavioural and physiological responses to stressors.

Effects of rearing condition on behavioural and physiological reaction to social confrontations and to social and non-social stressors were studied in female pigs. The pigs were reared under either poor (the standard farrowing crate) or enriched (group of free-ranging sows with piglets) conditions. At the age of 14-17 weeks, the pigs were exposed to a series of social confrontations where an intruder was introduced into the home pen of a resident. The results show the presence of a clear difference in terms of aggressive behaviour between residents and intruders from enriched but not from poor rearing conditions. Furthermore pigs reared under poor conditions inflicted more wounds on each other. We suggest that this reflects a difficulty in establishing a dominance relationship in poorly reared pigs, caused by impaired development of social skills in these pigs. Subsequently, reaction to novel object, non-social and social stress was measured in adult age, showing that the effects of rearing conditions are long-lasting, and give rise to differences in reaction to challenges in that pigs from enriched rearing conditions showed more avoidance behaviour than pigs from poor rearing conditions.

Rearing piglets in a poor environment: developmental aspects of social stress in pigs.

Effects of rearing conditions on the development of social relationships were investigated in female pigs. For that purpose, one group of piglets was reared in a poor environment (i.e., a commercially used indoor 4.2-m2 standard farrowing crate) and the other in an enriched environment (i.e., 0.5-ha outdoor pasture with half-open farrowing crates). After weaning, all piglets were housed in pairs under standard conditions. Dominant and subordinate individuals were distinguished within pairs and social relationships between members of a pair were studied in adulthood. The results show that pairs reared in a poor environment behave more aggressively. The subordinates of these pairs also develop symptoms indicative of chronic social stress exposure: i.e., they show a delayed onset of puberty, a smaller daily weight gain, and elevated basal cortisol levels that are also higher 5 h after an acute restraint stressor (tethering stress). No such deviations were found in subordinates reared in an enriched environment. It is concluded that rearing piglets in a poor environment may facilitate the development of social stress in adult (subordinate) pigs. Two underlying mechanisms may be proposed: a) deteriorated social skills lead to increased social stress, or b) a failure to cope with stressors in general, and the stress of being subordinate in particular, occurs in animals reared under poor conditions.

Technetium, the missing element.

The history of the discovery of technetium is reviewed within the framework of the discovery and production of artificial radioactivity in the twentieth century. Important elements of this history are the accidental production of this element in a cyclotron in Berkeley, California, USA, a machine devised by Ernest Orlando Lawrence, and its subsequent discovery in 1937 by Carlo Perrier and Emilio Segrè in scrap metal parts sent by Lawrence to Palermo, Italy by mail. A detailed account is given of the steps taken; the history of the later discovery of the technetium-99m isotope in 1938 is likewise examined. Sources of natural and artificial technetium are briefly discussed.

SDN-POA volume, sexual behavior, and partner preference of male rats affected by perinatal treatment with ATD.

The present study investigated 1) the importance of the aromatization process during the perinatal period for the development of the sexually dimorphic nucleus in the preoptic area of the hypothalamus (SDN-POA) of male rats, and 2) the relationship between SDN-POA volume and parameters of masculinization in male rats that were treated perinatally with the aromatase-inhibitor ATD. Males were treated with ATD either prenatally or pre- and neonatally, or with the vehicle. Masculine sexual behavior and partner preference were investigated in adulthood. Thereafter, animals were sacrificed and SDN-POA volume was measured. The SDN-POA volume was reduced in both the prenatally and the pre- and neonatally treated group, with a larger reduction in the latter than in the former group. Combined pre- and neonatal ATD treatment resulted in reduced frequency of mounts, intromissions, and ejaculations, as well as a reduced preference for a female over a male. The SDN-POA size was significantly and positively correlated with frequency of masculine sexual behavior, as well as preference for a female over a male.

Proceptive and receptive aspects of oestrus behaviour in gilts.

Proceptive and receptive aspects of behaviour were studied during the oestrus cycle of the female pig. These aspects were studied in a T-maze with one or two stimulus compartments that did or did not contain a teaser boar. Receptive behaviour was observed during several consecutive days and was quantified in front of the boar by using the back pressure test (BPT). Three aspects of proceptive behaviour, i.e. the tendency to 'search the boar', 'stay close to the boar' and 'to present' in front of the boar peaked in the middle of the receptive period, and in most gilts on the day preceding the last receptive day (Experiment 1). In contrast, preference for a particular boar, another aspects of proceptive behaviour, was only expressed during the days preceding and following the receptive period (Experiment 2). The results are discussed in terms of the possible functional implications of proceptive and receptive behaviour in relation to fertilization.

Lesions of the suprachiasmatic nucleus do not disturb sexual orientation of the adult male rat.

An enlarged suprachiasmatic nucleus (SCN) has been found earlier in a group of homosexual men, as compared to heterosexual controls. In order to assess a possible relationship between the SCN and sexual orientation, the present study was undertaken to investigate whether the rat SCN might play a role with respect to the expression of sexual orientation. Sexual orientation was measured in partner preference tests as the percentage of time spent in the vicinity of sexually active male and female incentives, that were separated from the experimental animal by a wire mesh. The results show that established patterns of sexual orientation towards female incentives by the adult male rat are not influenced by SCN-lesions. Disturbances in circadian rhythmicity of activity in SCN-lesioned animals did not affect this conclusion.

Cerebral glucose utilization during conditioned sexual arousal.

Local cerebral glucose utilization was investigated in male rats during conditioned sexual arousal. Increased glucose utilization was found in three amygdaloid nuclei after exposure to a stimulus associated with exposure to a sexually active female. No changes were observed in areas known to be of crucial importance for the expression of consummatory aspects of sexual behavior. These results corroborate and extend previous results showing a dissociation between the expression of appetitive and consummatory aspects of sexual behavior at a neural level.

Changes in male copulatory behavior after sexual exciting stimuli: effects of medial amygdala lesions.

A paradigm was developed to investigate how precoital sexual arousal affects parameters of sexual behavior in male rats. Estrous females in a wire mesh cage were used to induce sexual arousal before the sexual interaction test. In control procedures, males were presented in a wire mesh cage or else there was no stimuli at all. The results indicate that ejaculation latency is consistently reduced after preexposure to a female, but not after preexposure to a male, showing that the effect is specific for precoital sexual arousal. Other parameters were affected by precoital sexual arousal in some, but not in all experiments. Reductions in intromission latency moreover, were observed after both preexposure to a male and preexposure to a female, indicating that general social excitement affects this parameter. Preexposure to females for 10 minutes or 3 hours produced similar results. It was subsequently found that medial amygdala-lesioned (AME) animals differed from sham-lesioned (SHAM) controls with respect to their reaction to precoital sexual arousal. The results show that AME-lesioned animals, in contrast to SHAM-animals, do not show reduced ejaculation latencies after preexposure to an estrous female. The results are in line with the idea that AME-lesioned animals are deficient in the assimilation of information on sexual exciting stimuli.

Conditioned place preference induced by sexual interaction in female rats.

The present study was undertaken to establish whether the conditioned place preference paradigm can be utilized to investigate and elucidate the neuroendocrine basis of the appetitive elements of female sexual behavior. Females were exposed to a male with which copulation occurred in a distinctive compartment of the place preference apparatus and did not receive an incentive in the alternative compartment. After six pairings to each compartment a place preference test was conducted. Both estradiol benzoate and estradiol benzoate plus progesterone treated, ovariectomized females showed a preference for the compartment associated with sexual interaction. A second group of estradiol plus progesterone treated females was exposed to a male with which copulation occurred in one compartment of the place preference apparatus and to a sexually active, but caged, male in the other. The females tended to prefer the compartment paired with the caged male. After noncontingent intromissions, immediately preceding an additional test, the females showed a place preference for the compartment paired with sexual interaction. The presented observations indicate the potential use of the place preference procedure in studying opposing motivational processes associated with the unconditioned sequence of responses that characterize the species-specific pattern of sexual behavior.

Sciatic neuritis as initial symptom of spontaneous clostridial myonecrosis.

A 21-year-old woman is reported with aplastic anaemia, who presented with pain in the leg. Rapid loss of sciatic nerve function followed. MRI showed irregular streaks of low intensity in the muscles of the pelvic region. A diagnosis of sciatic neuritis as initial symptom of clostridial myonecrosis was made.

Scintigraphy in the clinical evaluation of disorders of mineral and skeletal metabolism in renal failure.

In patients with renal bone disease skeletal and extra-skeletal abnormalities can be visualised using conventional bone scintigraphy. Some of these abnormalities are associated with characteristic scintigraphic appearances, which are reviewed in detail, and the possible mechanisms involved are discussed. Specific imaging with iodine 123 serum amyloid P component and iodine 131 beta 2-microglobulin is also discussed in the diagnosis of beta 2-microglobulin amyloidosis specific to patients on dialysis. In the light of available evidence, it appears that bone scintigraphy plays, so far, a limited role in the clinical evaluation of skeletal and extra-skeletal abnormalities in chronic renal failure. The potential role of bone scintigraphy in identifying patients with aluminium-related bone disease needs to be investigated further, and in this respect special attention must be given to the problem of high soft-tissue activity associated with impaired renal function. Timing haemodialysis sessions before scintigraphic imaging deserves wider recognition as it reduces high soft-tissue activity, thereby allowing bone uptake to be assessed more accurately. Specific imaging of amyloidosis resulting from beta 2-microglobulin deposition is a promising technique, but the relative value of the two proposed radiopharmaceuticals needs further clarification.

Lesions of the SDN-POA inhibit sexual behavior of male Wistar rats.

Discrete bilateral lesions in the SDN-POA of sexually naive adult male rats were found to decrease the number of animals ejaculating and/or to increase latencies to the first mount, intromission and ejaculation. The deleterious effects of the lesions disappeared after 4 tests for sexual behavior but were reinstated when the males were tested under suboptimal conditions, i.e., when they were tested with a marginally receptive female or when they had only limited access to the stimulus female. It was subsequently shown that males with a bilaterally lesioned SDN-POA still showed an increase in plasma testosterone. LH and prolactin levels in response to sexual stimulation. Effects of the lesions on scent marking were not found. Together with previous data indicating that SDN-POA-lesions disrupt masculine sexual behavior in females, these data are taken as evidence that the SDN-POA plays a role in the regulation of masculine sexual behavior. The data further suggest that previously reported negative results of SDN-POA-lesions on masculine sexual behavior in male rats might be attributed to the use of sexually experienced instead of sexually inexperienced animals.

Sexual behavior and sexual orientation of the female rat after hormonal treatment during various stages of development.

The amount of circulating sex steroids during Postnatal Days 30-90 was varied in normally developed and in androgenized female rats. The influence of these manipulations on sexual behavior and sexual orientation was investigated. Normally developed or neonatally androgenized females were ovariectomized and implanted with estradiol through Postnatal Days 30-90 or sham-implanted. The remaining subjects were left intact during that period. The hormonal condition during Postnatal Days 30-90 significantly affected the behavior of normally developed females, but affected the behavior of neonatally androgenized females only to minor extent. Estrogen implants in normally developed females enhanced masculine sexual responses and induced a female-directed sexual orientation. Feminine sexual responses were unaffected by this treatment. Sham-implanted, normally developed females showed a male-directed sexual orientation and fewer masculine sexual responses than subjects which were left intact during Postnatal Days 30-90. Neonatal androgen treatment in general resulted in elevated levels of masculine Neonatal androgen treatment in general resulted in elevated levels of masculine sexual responses, inhibited feminine sexual behavior, and facilitated a female-directed sexual orientation.

Sexual experience and preference for males or females in the female rat.

The influence of sexual experience on preference behavior was investigated in adult female rats. In the first experiment, preference behavior for sexually active males versus estrous females was investigated in female rats who were experienced with mounting behavior. Preference of these mount experienced females was compared to preference of females who were naive in this respect. Mount experience with estrous females induced a female-directed preference in ovariectomized female rats, irrespective of whether the females were treated with OIL or with testosterone-propionate (500 micrograms TP, injected once 48 h prior to testing). Sexually naive, OIL-treated females did not show a preference for males or females, but TP induced a preference for a male. Individual differences in mount frequency were not correlated with preference behavior. In the second experiment, the influence of experience with feminine sexual responses on preference behavior was investigated. OIL-treated and TP-treated females oriented equally toward males and females when they had been given the opportunity to copulate with males prior to the preference tests. The results strongly suggest that prior sexual experience is an important determinant of preference behavior. The female's behavior during sexual interactions was, however, not predictive of later preference.