Expression and activation of caspase 3 following status epilepticus in the rat

It is in dispute whether caspase 3 contributes to status epilepticus (SE)-induced cell loss. We hypothesized that caspase 3-mediated cell death continues beyond the acute phase of SE. We induced SE with either kainic acid or electrical stimulation of the amygdala in Wistar and Sprague-Dawley rats. Caspase 3 immunohistochemistry, Western blot analysis and enzyme activity measurements were used to determine cellular localization and the time course of caspase 3 expression and activation. Immunohistochemistry indicated that caspase 3 protein expression increased following SE, peaking at 16-24 h. Cleavage of procaspase 3 to active fragments (p20-17) was detected 2-7 days after SE. Caspase 3 enzyme activity was elevated at 8 h and further increased up to 19.4-fold at 7 days following SE. Activation of caspase 3 after SE occurred in the hippocampus and the extrahippocampal temporal lobe but not in the thalamus. Caspase 3-immunoreactive cells represented only a minority of degenerating cells as assessed by Fluoro-Jade B and TUNEL staining. Analysis of double-labelled sections indicated that active caspase 3 was located in astrocytes rather than neurons or microglia. There was increased caspase 3 expression in both rat strains, and it was independent of the method used to induce SE. These data demonstrate that caspase 3 contributes to the cell death occurring within the first week after SE, but in only a small proportion of degenerating cells. These results suggest that, contrary to expectations, caspase 3 inhibitors would have only limited benefits in the treatment of SE.     

Ovarian age-related responsiveness to human chorionic gonadotropin in women with polycystic ovary syndrome

Ovarian steroid secretion capacity starts to decline as early as around the age of 30 yr. Whether an age-related decrease in androgen secretion, as in normal women, also occurs in women with polycystic ovary syndrome (PCOS) and whether the enhanced androgen production in PCOS remains throughout the fertile period of life are not known. The aim of this study was to determine the age-related serum basal and gonadotropin-stimulated androgen levels in women with PCOS and to compare the results with those obtained from our previous study in healthy women with normal ovaries. Human chorionic gonadotropin (hCG) stimulation tests were carried out among 42 women with PCOS (age, 16-44 yr; body mass index, 31.02 +/- 1.1 kg/m(2)). An im injection of 5000 IU hCG was given 2-4 d after spontaneous or progestin-induced menstrual bleeding, and blood samples for LH, FSH, inhibin B, 17-hydroxyprogesterone, androstenedione (A), testosterone (T), and estradiol assays were collected at 0, 24, 48, and 96 h. In women with PCOS, basal serum T and A levels were about 50% higher than in healthy women. The responses of A and T to hCG [area under the curve (AUC), 96 h)] were significantly higher in women with PCOS than in normal women [A, 1183.6 +/- 60 (+/-se) vs. 814.4 +/- 39 (P 相似文献   

Postmortem measurement of C-reactive protein and interpretation of results in ketoacidosis

C-reactive protein (CRP) is a widely used acute phase protein that reacts to various tissue-destroying stimuli. Its forensic applications have been established in prior studies. We show that CRP can be successfully measured even after a long postmortem period, up to 18 days, which has not previously been reported. Information on elevated CRP levels can be very valuable for the forensic pathologist in autopsy cases with scarce findings. The interpretation of results can be very challenging, as the elevation can originate from many different reasons, and due to the biochemical changes in cadavers. One less studied possible reason for elevated CRP is ketoacidosis. Here, we present a study on the effect of both alcoholic and diabetic ketoacidosis on blood CRP elevation in forensic autopsy material. Our results imply that ketoacidosis itself can cause a rise in CRP without other underlying causes, such as infection or trauma. However, more comprehensive studies are required to confirm the relationship between ketoacidosis and CRP level elevation.     

Nurse–surgeon object transfer: Video analysis of communication and situation awareness in the operating theatre

Background

One of the most central collaborative tasks during surgical operations is the passing of objects, including instruments. Little is known about how nurses and surgeons achieve this. The aim of the present study was to explore what factors affect this routine-like task, resulting in fast or slow transfer of objects.

Methods

A qualitative video study, informed by an observational ethnographic approach, was conducted in a major teaching hospital in the UK. A total of 20 general surgical operations were observed. In total, approximately 68 h of video data have been reviewed. A subsample of 225 min has been analysed in detail using interactional video-analysis developed within the social sciences.

Results

Two factors affecting object transfer were observed: (1) relative instrument trolley position and (2) alignment. The scrub nurse's instrument trolley position (close to vs. further back from the surgeon) and alignment (gaze direction) impacts on the communication with the surgeon, and consequently, on the speed of object transfer. When the scrub nurse was standing close to the surgeon, and “converged” to follow the surgeon's movements, the transfer occurred more seamlessly and faster (<1.0 s) than when the scrub nurse was standing further back from the surgeon and did not follow the surgeon's movements (>1.0 s).

Conclusions

The smoothness of object transfer can be improved by adjusting the scrub nurse's instrument trolley position, enabling a better monitoring of surgeon's bodily conduct and affording early orientation (awareness) to an upcoming request (changing situation). Object transfer is facilitated by the surgeon's embodied practices, which can elicit the nurse's attention to the request and, as a response, maximise a faster object transfer. A simple intervention to highlight the significance of these factors could improve communication in the operating theatre.     

Homozygosity analysis in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) may appear to be familial or sporadic, with recognised dominant and recessive inheritance in a proportion of cases. Sporadic ALS may be caused by rare homozygous recessive mutations. We studied patients and controls from the UK and a multinational pooled analysis of GWAS data on homozygosity in ALS to determine any potential recessive variant leading to the disease. Six-hundred and twenty ALS and 5169 controls were studied in the UK cohort. A total of 7646 homozygosity segments with length >2 Mb were identified, and 3568 rare segments remained after filtering ‘common'' segments. The mean total of the autosomal genome with homozygosity segments was longer in ALS than in controls (unfiltered segments, P=0.05). Two-thousand and seventeen ALS and 6918 controls were studied in the pooled analysis. There were more regions of homozygosity segments per case (P=1 × 10⁻⁵), a greater proportion of cases harboured homozygosity (P=2 × 10⁻⁵), a longer average length of segment (P=1 × 10⁻⁵), a longer total genome coverage (P=1 × 10⁻⁵), and a higher rate of these segments overlapped with RefSeq gene regions (P=1 × 10⁻⁵), in ALS patients than controls. Positive associations were found in three regions. The most significant was in the chromosome 21 SOD1 region, and also chromosome 1 2.9–4.8 Mb, and chromosome 5 in the 65 Mb region. There are more than twenty potential genes in these regions. These findings point to further possible rare recessive genetic causes of ALS, which are not identified as common variants in GWAS.     

The Deleterious Effects of High Inbreeding on Male Drosophila melanogaster Attractiveness are Observed Under Competitive but not Under Non-competitive Conditions

In order for the male courtship traits to honestly signal quality they need to be condition-dependent. Moreover, if these traits capture genetic variation in condition they should resemble life-history traits in being subject to strong directional selection and, consequently, suffer strong inbreeding depression. In this study we investigated the effect of high inbreeding on male attractiveness by assessing mating success, mating speed and copulation duration of inbred, outbred and crossbred (constructed by crossing separate, randomly chosen inbred lines) males of Drosophila melanogaster. When set to compete against a standardized competitor and compared to the success rate of the crossbred lines, inbreeding significantly reduced male mating success. Under competition, outbred males initiated copulation significantly sooner than crossbred and inbred males. Under non-competitive conditions, no effect of inbreeding was found on either mating speed or copulation duration. Both mating success and mating speed showed much higher inbreeding depression than male size.