Rectal Absorption Enhancement of Des-Enkephalin-γ-Endorphin (DEγE) by Medium-Chain Glycerides and EDTA in Conscious Rats

The stability of the neuroleptic peptide des-enkephalin--endorphin (DEE; Org 5878) in the rectal lumen and the rectal bioavailability of DEE were investigated in conscious rats. Furthermore, the influence of peptidase inhibition, peptidase saturation, and absorption enhancement on DEE bio-availability were evaluated. Na₂EDTA (0.25%, w/v) prolonged the degradation half-life of DEE in the ligated colon from 33 ± 7 to 93 ± 45 min. Without adjuvant, tritium-labeled DEE was absorbed from the rat rectum to a very low extent (0–4%). After administration of an excess of unlabeled DEE or with Na₂EDTA, comparable results were obtained. The medium-chain glyceride preparation MGK markedly enhanced the rectal DEE bioavailability, up to 8–20%, which was further increased to 10–44% by coadministration of Na₂EDTA. No substantial influence of varying the rectal delivery rate was observed. The results suggest that absorption enhancement and enzyme inhibition both are essential for effective increase of rectal peptide bioavailability.     

Inefficient in vivo neutrophil migration in neonatal rats

While neutrophils from neonates respond less efficiently in vitro to a chemotactic stimulus than do adult cells, the in vivo recruitment of phagocytic cells to focal sites of inflammation in some situations appears to be similar in adults and neonates. To resolve this apparent discrepancy between the in vitro and in vivo observations, neonatal and adult rats were inoculated intraperitoneally with a variety of chemotactic agents. The neutrophil response was far more intense in adults than in neonates, strengthening the hypothesis that chemotaxis is less efficient in neonates than in adults. This relative deficiency may play an important role in the inability of the newborn to deal with infection effectively.     

The development of lymphocytes with T- or B-membrane determinants in the human foetus

The development of T- or B-membrane determinants on human foetal lymphoid cells was studied by the direct immunofluorescence technique, using a tetramethyl rhodamine isothiocyanate (TRITC) labelled horse antihuman T-cell conjugate (ATC) for the detection of T lymphocytes and a fluorescein isothiocyanate (FITC) labelled goat antihuman Fab conjugate for the demonstration of Ig-bearing B lymphocytes. Human foetal lymphocytes were also tested for spontaneous rosette formation with sheep red blood cells (SRBC).

Cell suspensions of liver, spleen, thymus, bone marrow and blood of twenty-five human foetuses of 5·5–26 weeks of gestational age have been investigated. ATC-positive lymphoid cells were first seen in the liver at 5·5 weeks; E rosette-forming cells (ERFC) and Ig-bearing lymphoid cells were first found at 9 weeks. ERFC were also present in the thymus at 9 weeks. By 12 weeks, fluorescent B and T lymphocytes were found in bone marrow and spleen. ERFC were also found in bone marrow at this age, but not in spleen. At 15 weeks, more than 80% of blood lymphoid cells had T or B determinants.

A difference in the reactivity of lymphoid cells with the ATC and their capacity to form E rosettes was observed. In liver and spleen, the ATC determinant was detectable before the SRBC receptor. In bone marrow, blood and thymus the ATC determinant was found on a higher percentage of lymphoid cells than was the SRBC receptor when those organs were first investigated. During the entire investigated period of gestation, the majority of lymphoid cells in liver and bone marrow did not react with either of the conjugates, nor did they form E rosettes. In all organs investigated, except in the thymus, lymphoid cells were occasionally seen which reacted with both conjugates. By the 16th week of foetal age, more than 90% of lymphoid cells in thymus, spleen and blood had acquired T- or B-membrane determinants.

     

The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry

Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell- mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ- specific autoimmune disease.      

Leisure time physical activity and health-related quality of life: Cross-sectional and longitudinal associations

Studies that relate change in physical activity to change in health-related quality of life in the general population are needed to confirm associations suggested by cross-sectional studies. In the present study, cross-sectional as well as longitudinal associations between leisure time physical activity and health-related quality of life were studied in an apparently healthy population. The present study showed cross-sectional associations between at least moderately intense leisure time physical activity and general health perceptions, vitality, physical functioning and role limitations due to physical health problems. No associations were present for total leisure time physical activity. Change in leisure time physical activity was associated with change in social functioning in men as well as in women, irrespective of the intensity of physical activity. Only in men, change in total leisure time physical activity was associated with change in vitality and general mental health. In our study, cross-sectional associations were not confirmed by longitudinal analyses. Cross-sectional associations were mainly found for physical components of health-related quality of life, whereas longitudinal associations were predominantly observed for mental components of health-related quality of life. Confirmation of our results by those of other studies is needed in order to quantify health promotion messages.     

Why STAN might not be dead

Recently, a meta-analysis, including 26?526 laboring vertex singletons at term, summarized all available level-1 data from six high-quality randomized clinical trials (RCTs) on the use of ST analysis (STAN) during labor as an adjunct to conventional intrapartum fetal heart rate monitoring. The meta-analysis showed that STAN did not improve perinatal outcomes or decrease cesarean deliveries. Nonetheless, there are still reasons to believe STAN may have a role in the future research on intrapartum fetal monitoring. Out of six trials included in the meta-analysis, two included all cephalic singletons in labor, and four enrolled only high-risk pregnant women. This combination of both low- and high-risk populations may have distorted the potential impact of STAN. The test for heterogeneity between both subgroups was found to be statistically significant, indicating that the effect of STAN was different in high-risk women compared to a combination of both low- and high-risk women. Furthermore, the classifications of the fetal heart rate patterns used in the included randomized trials were different. Last but not least, despite?>26?000 women with singleton gestations were included in the meta-analysis, the evidence still suffers from a lack of power, especially for subgroup analyses. In summary, while the level-1 data so far indicate overall no perinatal benefit of adding STAN to conventional intrapartum fetal heart rate monitoring for the outcomes most of interest, several issues point to the fact that more research is needed before the STAN technology can be deemed of no value for fetal monitoring in labor.     

Brain CT perfusion improves intracranial vessel occlusion detection on CT angiography

Background and purpose

To evaluate whether brain CT perfusion (CTP) aids in the detection of intracranial vessel occlusion on CT angiography (CTA) in acute ischemic stroke.