Distribution of the Receptor for Advanced Glycation End Products (RAGE) in the Human Male Reproductive Tract. Prevalence in Men with Diabetes Mellitus.

BACKGROUND: Diabetics have a significantly higher percentage of sperm with nuclear DNA (nDNA) fragmentation and increased levels of advanced glycation end products (AGEs), in their testis, epididymis and sperm. As the receptor for AGEs (RAGE) is important to oxidative stress and cell dysfunction, we hypothesise, that it may be involved in sperm nDNA damage. METHODS: Immunohistochemistry was performed to determine the presence of RAGE in the human testis and epididymis. A comparison of the receptor's incidence and localisation on sperm from 10 diabetic and 11 non-diabetic men was conducted by blind semi-quantitative assessment of the immunostaining. ELISA analysis ascertained RAGE levels in seminal plasma and sperm from 21 diabetic and 31 non-diabetic subjects. Dual labelling immunolocalisation was employed to evaluate RAGE's precise location on the sperm head. RESULTS: RAGE was found throughout the testis, caput epididymis, particularly the principle cells apical region, and on sperm acrosomes. The number of sperm displaying RAGE and the overall protein amount found in sperm and seminal plasma were significantly higher in samples from diabetic men (p

Advanced Glycation End Products (AGEs) accumulate in the Reproductive Tract of Men with Diabetes.

Light microscopic studies comparing sperm parameters show little association between diabetes and male fertility. However, with the introduction of new analytical techniques, evidence is now emerging of previously undetectable affects of diabetes on sperm function. Specifically, a recent study has found significantly higher sperm nuclear DNA (nDNA) fragmentation in diabetic men. As advanced glycation end products (AGEs) are important instigators of oxidative stress and cell dysfunction in numerous diabetic complications, we hypothesized that these compounds could also be present in the male reproductive tract. The presence and localization of the most prominent AGE, carboxymethyl-lysine (CML), in the human testis, epididymis and sperm was determined by immunohistochemistry. Parallel ELISA and Western blot analyses were performed to ascertain the amount of CML in seminal plasma and sperm from 13 diabetic and 9 non-diabetic subjects. CML immunoreactivity was found through out the seminiferous epithelium, the nuclei of spermatogonia and spermatocytes, in the basal and principle cells (cytoplasm and nuclei) of the caput epididymis and on most sperm tails, mid pieces and all cytoplasmic droplets. The acrosomal cap, especially the equatorial band, was prominently stained in diabetic samples only. The amount of CML was significantly higher (p = 0.004) in sperm from non diabetic men. Considering the known detrimental actions of AGEs in other organs, the presence, location and quantity of CML, particularly the increased expression found in diabetic men, suggests that these compounds may play a hitherto unrecognized role in male infertility.

Advanced glycation end products accumulate in the reproductive tract of men with diabetes

Light microscopic studies comparing sperm parameters show little association between diabetes and male fertility. However, with the introduction of new analytical techniques, evidence is now emerging of previously undetectable effects of diabetes on sperm function. Specifically, a recent study has found a significantly higher sperm nuclear DNA fragmentation in diabetic men. As advanced glycation end products (AGEs) are important instigators of oxidative stress and cell dysfunction in numerous diabetic complications, we hypothesized that these compounds could also be present in the male reproductive tract. The presence and localization of the most prominent AGE, carboxymethyl-lysine (CML), in the human testis, epididymis and sperm was determined by immunohistochemistry. Parallel ELISA and Western blot analyses were performed to ascertain the amount of CML in seminal plasma and sperm from 13 diabetic and nine non-diabetic subjects. CML immunoreactivity was found throughout the seminiferous epithelium, the nuclei of spermatogonia and spermatocytes, in the basal and principle cells cytoplasm and nuclei of the caput epididymis and on most sperm tails, mid pieces and all cytoplasmic droplets. The acrosomal cap, especially the equatorial band, was prominently stained in diabetic samples only. The amount of CML was significantly higher (p = 0.004) in sperm from non-diabetic men. Considering the known detrimental actions of AGEs in other organs, the presence, location and quantity of CML, particularly the increased expression found in diabetic men, suggest that these compounds may play a hitherto unrecognized role in male infertility.

Linking past cultural developments to palaeoenvironmental changes in Estonia

Connections between environmental and cultural changes are analysed in Estonia during the past c. 4,500 years. Records of cereal-type pollen as (agri)cultural indices are compared with high-resolution palaeohydrological and annual mean temperature reconstructions from a selection of Estonian bogs and lakes (and Lake Igelsjon in Sweden). A broad-scale comparison shows increases in the percentage of cereal-type pollen during a decreasing trend in annual mean temperatures over the past c. 4,300 years, suggesting a certain independence of agrarian activities from environmental conditions at the regional level. The first cereal-type pollen in the region is found from a period with a warm and dry climate. A slow increase in pollen of cultivated land is seen around the beginning of the late Bronze Age, a slight increase at the end of the Roman Iron Age and a significant increase at the beginning of the Middle Ages. In a few cases increases in agricultural pollen percentages occur in the periods of warming. Stagnation and regression occurs in the periods of cooling, but regression at individual sites may also be related to warmer climate episodes. The cooling at c. 400-300 cal b.p., during the 'Little Ice Age' coincides with declines in cereal-type and herb pollen curves. These may not, however, be directly related to the climate change, because they coincide with war activities in the region.

Rapid ecosystem response to abrupt climate changes during the last glacial period in western Europe, 40-16 ka

We present a high-resolution and independently dated multiproxy lake sediment record from the paleolake at Les Echets in southeastern France that displays synchronous changes in independent limnic and terrestrial ecosystem proxies, in concert with millennial-scale climate oscillations during the last glacial period. Distinct lake-level fluctuations, low lake organic productivity, and open, treeless vegetation indicate cold and dry conditions in response to Heinrich events. Alternating phases of higher and low lake organic productivity, stratified surface waters and long-lasting lake ice cover, decreased or increased catchment erosion, and tree-dominated or herb-dominated vegetation resemble Dansgaard-Oeschger interstadial-stadial variability. Transitions between different ecological states occurred in as little as 40-230 yr and seem to have been controlled by the position of the Polar Front. Ecosystem response after 30 ka suggests that local climate conditions became more important. Our results demonstrate that all parts of the terrestrial system responded to the abrupt and dramatic climatic changes associated with Dansgaard-Oeschger and Heinrich events, and that regional factors modulated ecosystem response.

Evidence of natural occurrence of the banned antibiotic chloramphenicol in herbs and grass

Chloramphenicol (CAP), a broad-spectrum antibiotic, was detected in several herb and grass samples from different geographic origins. Due to its suspected carcino-genicity and linkages with the development of aplastic anemia in humans, CAP is banned for use in food-producing animals in the European Union (EU) and many other countries. However, products of animal origin originating from Asian countries entering the European market are still found noncompliant (containing CAP) on a regular basis, even when there is no history of chloramphenicol use in these countries. A possible explanation for the continued detection of these residues is the natural occurrence of CAP in plant material which is used as animal feed, with the consequent transfer of the substance to the animal tissues. Approximately 110 samples were analyzed using liquid chromatography coupled with mass spectrometric detection. In 26 samples, the presence of CAP was confirmed using the criteria for banned substances defined by the EU. Among other plant materials, samples of the Artemisia family retrieved from Mongolia and from Utah, USA, and a therapeutic herb mixture obtained from local stores in the Netherlands proved to contain CAP at levels ranging from 0.1 to 450 mu g/kg. These findings may have a major impact in relation to international trade and safety to the consumer. The results of this study demonstrate that noncompliant findings in animal-derived food products may in part be due to the natural occurrence of chloramphenicol in plant material. This has implications for the application of current EU, USA, and other legislation and the interpretation of analytical results with respect to the consideration of CAP as a xenobiotic veterinary drug residue and the regulatory actions taken upon its detection in food.

The Holocene vegetation cover of Britain and Ireland: overcoming problems of scale and discerning patterns of openness

The vegetation of Europe has undergone substantial changes during the course of the Holocene epoch, resulting from range expansion of plants following climate amelioration, competition between taxa and disturbance through anthropogenic activities. Much of the detail of this pattern is understood from
decades of pollen analytical work across Europe, and this understanding has been used to address questions relating to vegetation-climate feedback, biogeography and human impact. Recent advances in modelling the relationship between pollen and vegetation now make it possible to transform pollen
proportions into estimates of vegetation cover at both regional and local spatial scales, using the Landscape Reconstruction Algorithm (LRA), i.e. the REVEALS (Regional Estimates of VEgetation Abundance from Large Sites) and the LOVE (LOcal VEgetation) models. This paper presents the compilation and analysis of 73 pollen stratigraphies from the British Isles, to assess the application of the LRA and describe the pattern of landscape/woodland openness (i.e. the cover of low herb and bushy vegetation) through the Holocene. The results show that multiple small sites can be used as an effective replacement for a single large site for the reconstruction of regional vegetation cover. The REVEALS vegetation estimates imply that the British Isles had a greater degree of landscape/woodland openness at the regional scale than areas on the European mainland. There is considerable spatial bias in the British Isles dataset towards wetland areas and uplands, which may explain higher estimates of landscape openness compared with Europe. Where multiple estimates of regional vegetation are available from within the same region inter-regional differences are greater than intra-regional differences, supporting the use of the REVEALS model to the estimation of regional vegetation from pollen data.