Dithiothreitol prevents age-associated decrease in oocyte/conceptus viability in vitro

The present study was designed to ascertain whether the negative effects on reproductive potential of post-ovulatory ageing in vitro of oocytes can be prevented by antioxidant therapy. Mouse metaphase II (MII) oocytes were aged in vitro for 12 h prior to insemination in the presence of varying concentrations of L-ascorbic acid, 6-methoxy- 2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), L-cystine dihydrochloride, ethylenediaminetetraacetic acid (EDTA), beta- mercaptoethanol and DL-dithiothreitol (DTT). In-vitro ageing of oocytes was associated with lower fertilization rate, higher proportion of concepti exhibiting cellular fragmentation at 24 h post-insemination and lower percentage of concepti reaching the blastocyst stage. Ascorbic acid, Trolox and EDTA had no effect on cellular fragmentation or potential of oocytes for development. However, the probability of an oocyte reaching the blastocyst stage was decreased (P < or = or = 0.05) in oocytes incubated in the presence of L-cystine (50 and 500 microM) and beta-mercaptoethanol (5, 50 and 500 microM) when compared to control aged oocytes. Age-associated cellular fragmentation at 24 h post-insemination was partially prevented (P < or = 0.05) by incubating oocytes in the presence of beta-mercaptoethanol (500 microM). DTT (50 and 500 microM) increased (P < or = 0.05) fertilization rate and number of cells at 81 h post-insemination to levels similar to those exhibited by control oocytes. Furthermore, both age-associated fragmentation at 24 h post-insemination (P < or = 0.05) and decreased potential of oocytes for development to the blastocyst stage (P < or = 0.05) were prevented, at least in part, by culturing oocytes in the presence of DTT (50 microM). Although the mechanism by which DTT exerts its beneficial effects on aged oocytes remains to be elucidated, it may protect oocytes by preventing oxidation of free thiol groups and/or altering a redox-independent signalling pathway that mediates cellular fragmentation and death.      

Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection

Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic sperm injection (ICSI) resulted in the detection of nine (12.7%) chromosome aberrations including two cases of 47,XXY, four cases involving a 45,X cell line and three autosomal trisomies. Molecular analysis of the parental origin of the deleted or supernumerary chromosome was performed by using polymorphic microsatellite markers. Six cases involving a sex chromosome abnormality were found to be of paternal origin while the two trisomic cases that could be analysed were of maternal origin. Two cases involved the same infertile couple who had two consecutive ICSI pregnancies terminated because of a chromosome abnormality. The replaced embryos in both cases originated from a single batch of ICSI fertilized oocytes of which part was used to initiate the first pregnancy and part was cryopreserved and used to initiate the second pregnancy.      

Amygdaloid inhibition of maternal behavior in the nulliparous female rat

In the first experiment, the effects of lesions of (1) the amygdala, (2) its major efferent projection system, the stria terminalis or (3) other non-limbic brain sites on the induction of maternal behavior in the nulliparous female rat were investigated. Animals sustaining lesions of either the amygdala or the stria terminalis became maternal more rapidly than did control animals. In the second study the effects of lesions to different portions of the amygdala on both maternal and fear responding were investigated. It was found that animals sustaining damage to the corticomedial amygdaloid nuclei became maternal more quickly than did animals sustaining either basolateral amygdaloid damage or no amygdaloid damage. Also in comparison to lesioned controls, animals with lesions of the amygdala showed reduced ‘fearfulness’ on a number of fear-mediated tasks. The third study attempted to interrelate fear responsiveness and maternal behavior by observing nulliparous animals with amygdaloid or stria terminalis lesions for their responses to unfamiliar foster pups placed daily into their preferred nesting quadrant. While control animals actively avoided pups placed into their nest sites (by moving their nest site to another quadrant of the cage), animals with amygdaloid lesions or lesions of the stria terminalis, did not. These results are interpreted to mean that nulliparous females generally do not respond maternally to pups because these females are, in general, more neophobic than parturient females and they tend to find pups and their novel odors, aversive. This aspect of their behavior is likely mediated by the amygdala. These data are discussed in terms of their relevance to the rapid maternal responsiveness normally shown by the female at parturition.     

Self-administration of intravenous amphetamine: effect of nucleus accumbens CCKB receptor activation on fixed-ratio responding

Rationale: The mesolimbic dopamine (DA) system is implicated in psychostimulant drug self-administration. The neuropeptide cholecystokinin (CCK) is co-localised with DA and inhibits nucleus accumbens (NAcc) DAergic neurotransmission via CCK_B receptors. Objectives: The present experiment was designed to examine the effects of intra-NAcc CCK_B receptor stimulation on fixed-ratio (FR) amphetamine self-administration. Methods: Wistar rats with intravenous catheters and NAcc cannulae were trained to self-administer amphetamine under a FR3 schedule of reinforcement. Animals performing stable self-administration were microinjected with pentagastrin and assessed during 3-h sessions. Results: Intra-NAcc pentagastrin dose dependently increased amphetamine intake. Conclusions: These results are consistent with the notion that NAcc CCK_B receptor activation attenuates amphetamine reward. Received: 6 May 1999 / Final version: 4 August 1999     

Situational management

In this paper, the organizational theory of situational planning is used to establish a decentralized management model for complex health units. Because of cultural limitations imposed on a perspective of change and rationalization, considerations are made in relation to a given form of dealing with culture, keeping in mind the feasibility of the management model. A particular type of communicative management emerges as a general need revealed by the analysis of the object at issue: the management of professional organizations.     

Auditing paediatric diabetes care and the impact of a specialist nurse trained in paediatric diabetes

AIMS: To define outcome measures for auditing the clinical care of children and adolescents with insulin dependent diabetes mellitus (IDDM) and to assess the benefit of appointing a dedicated paediatric trained diabetes specialist nurse (PDSN). METHODS: Retrospective analysis of medical notes and hospital records. Glycaemic control, growth, weight gain, microvascular complications, school absence, and the proportion of children undergoing an annual clinical review and diabetes education session were assessed. The effect of the appointment of a PDSN on the frequency of hospital admission, length of inpatient stay, and outpatient attendance was evaluated. RESULTS: Children with IDDM were of normal height and grew well for three years after diagnosis, but grew suboptimally thereafter. Weight gain was above average every year after diagnosis. Glycaemic control was poor at all ages with only 16% of children having an acceptable glycated haemoglobin. Eighty five per cent of patients underwent a formal annual clinical review, of whom 16% had background retinopathy and 20% microalbuminuria in one or more samples. After appointing the PDSN the median length of hospital stay for newly diagnosed patients decreased from five days to one day, with 10 of 24 children not admitted. None of the latter was admitted during the next year. There was no evidence of the PDSN affecting the frequency of readmission or length of stay of children with established IDDM. Non-attendance at the outpatient clinic was reduced from a median of 19 to 10%. CONCLUSIONS: Outcome measures for evaluating the care of children with IDDM can be defined and evaluated. Specialist nursing support markedly reduces the length of hospital stay of newly diagnosed patients without sacrificing the quality of care.     

Tuberous sclerosis complex and Wolff-Parkinson-White syndrome

This report highlights the association between tuberous sclerosis and Wolff-Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff-Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson-White syndrome presented early in life, nine cases being diagnosed in the first year. Eight of the 10 cases were male. In eight cases, the syndrome was associated with supraventricular tachycardias, and in nine with cardiac rhabdomyomata. One child died from cardiac failure secondary to obstruction of the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory pathway was localised in nine patients from surface electrocardiograms: six children had left sided pathways and three had right sided pathways.